Version July 2025
INTRODUCTION —
Hematopoietic cell transplantation (HCT) refers to treatment of a patient (the transplant recipient) with a preparative (conditioning) regimen, followed by an infusion of hematopoietic stem/progenitor cells. The conditioning regimen generally includes intensive chemotherapy, radiation therapy, and/or an immunotherapeutic agent that partially or fully abrogates the ability of the recipient (the "host") to recover blood formation. Infusion of hematopoietic stem and progenitor cells (the "graft") reconstitutes hematopoiesis.
The graft in allogeneic transplantation is from a related or unrelated individual ("donor") who is chosen based on immune compatibility. The graft itself can be obtained from bone marrow, peripheral blood, or umbilical cord blood. By contrast with allogeneic transplantation, autologous HCT refers to transplantation in which the graft is the transplant recipient's own stored hematopoietic cells.
Allogeneic HCT is used to treat various hematologic neoplasms and nonmalignant marrow disorders, including acquired and inherited conditions. Eligibility of a potential allogeneic HCT recipient is made on a case-by-case basis. Eligibility criteria vary across countries and institutions.
This topic discusses indications, eligibility, and estimating prognosis for allogeneic HCT.
Related topics include:
●(See "Donor selection for hematopoietic cell transplantation".)
●(See "Hematopoietic cell transplantation (HCT): Sources of hematopoietic stem/progenitor cells".)
●(See "Hematopoietic support after hematopoietic cell transplantation".)
●(See "Early complications of hematopoietic cell transplantation".)
●(See "Long-term care of the adult hematopoietic cell transplantation survivor".)
●(See "Determining eligibility for autologous hematopoietic cell transplantation".)
OVERVIEW OF ALLOGENEIC HCT —
Allogeneic HCT involves replacing a transplant recipient's diseased hematopoietic cells with hematopoietic cells from another individual.
Conditioning therapy (ie, chemotherapy, radiation therapy [RT], immunotherapy, or a combination) is used to reduce or eliminate the burden of the transplant recipient's dysfunctional cells. The diseased cells of the transplant recipient (the "host") are replaced by healthy cells from an immunologically compatible donor. When allogeneic HCT is used to treat a malignancy, subtle immunologic differences between the donor's transplanted hematopoietic cells (the "graft") and the recipient's cancer cells contribute a graft-versus-tumor (GVT) effect, which is important for achieving long-term disease control/cure.
However, immunologic differences between the graft and the host also contribute to graft-versus-host disease (GVHD; systemic injury to skin, gastrointestinal tract, lungs, and other organs) that causes substantial morbidity and potential mortality in the recipient. Immunosuppressive agents that are used to prevent and/or treat GVHD and the conditioning regimen also contribute to the toxicity of allogeneic HCT.
An overview of key aspects of allogeneic HCT follows.
Graft selection — Allogeneic HCT requires an immunologically compatible hematopoietic graft from a transplant donor. Human leukocyte antigens (HLAs) are the major determinants of immune compatibility, but there are also minor antigens that might influence donor choice.
●Donor – The graft donor refers to the person who provides the hematopoietic graft. The donor can be related to the recipient (because of the high likelihood of sharing at least some HLA antigens) or the donor can be an unrelated individual.
•Related – Related donors may be siblings (eg, HLA-matched sibling donor [MSD]) or they can be parents, children, or other close relatives who share one-half of the HLA antigens with the patient (ie, HLA-haploidentical donors).
•Unrelated – HLA-matched grafts can also be from an unrelated donor (matched unrelated donor [MUD]).
In some cases, the graft can be obtained from umbilical cord blood (UCB).
The selection of an allogeneic donor is discussed separately. (See "Donor selection for hematopoietic cell transplantation".)
Discussions of HLA organization, function, and typing are presented separately. (See "Human leukocyte antigens (HLA): A roadmap".)
●Source – The graft can be obtained from either bone marrow or blood.
The choice of graft source is informed by the underlying disease (eg, malignant versus nonmalignant) and the recipient's age (ie, child versus adult). Grafts from bone marrow, peripheral blood, and UCB are associated with different yields of stem/progenitor cells; timing of blood count recovery and immune reconstitution; and risks for GVHD, relapse, and infections. The choice of graft source is discussed separately. (See "Hematopoietic cell transplantation (HCT): Sources of hematopoietic stem/progenitor cells".)
Whatever the graft source, the hematopoietic cells are administered intravenously and they promptly migrate to the bone marrow to begin the process of engraftment. Hematopoietic grafts are not surgically implanted in the bone marrow.
Conditioning therapy — Conditioning therapy (also called preparative therapy) refers to treatments that are used to reduce the burden of diseased cells (hematopoietic stem/progenitor cells and lymphoid cells) prior to graft infusion.
The conditioning regimen may include chemotherapy, RT, immunotherapeutic agents, or a combination of these components. There are two broad categories of preparative regimens (figure 1) [1]:
●High intensity – Myeloablative conditioning (MAC) regimens are intensive treatments that eliminate nearly all host bone marrow cells, resulting in an inability to spontaneously recover host hematopoiesis.
MAC regimens are often used to treat hematologic malignancies in patients who can tolerate the substantial adverse effects (AEs). Many centers limit MAC allogeneic HCT to patients <55 years because of potential organ toxicity.
●Lower intensity – Nonmyeloablative conditioning (NMA) or reduced-intensity conditioning (RIC) are less intensive than MAC and do not fully abolish host hematopoiesis. These regimens initially result in a chimeric state (ie, both host and donor hematopoiesis), but donor hematopoiesis becomes increasingly dominant over time.
NMA/RIC regimens are often used in patients ≥55 to 75 years or older, but they may be preferred for younger patients with substantial comorbidities and/or conditions that do not require complete eradication of host marrow cells (eg, nonmalignant disorders).
Selection of a preparative regimen is informed by patient age, comorbidities, underlying disease (eg, hematologic malignancy versus nonmalignant disorders), and institutional approach, as discussed separately. (See "Preparative regimens for hematopoietic cell transplantation".)
Toxicity — Allogeneic HCT is associated with substantial short-term and long-term morbidity and potential transplant-related mortality.
Causes — Aspects of allogeneic HCT that contribute to its toxicity include:
●Conditioning regimen – The preparative regimen can cause organ damage (most often involving liver, kidney, heart, or lungs), infectious complications, and profound and prolonged cytopenias until the transplanted cells engraft.
Close monitoring and attentive care are required for the successful management of these complications, as described separately. (See "Hematopoietic support after hematopoietic cell transplantation".)
●GVHD – Immunologic mismatch between HLA and/or minor antigens can trigger GVHD, in which engrafted donor cells attack the host's skin, mucosa, gastrointestinal tract, liver, lungs, and possibly other organs.
Some manifestations of GVHD begin relatively soon after graft infusion (acute GVHD; eg, typically within 100 days), while others generally begin weeks or months later (chronic GVHD), but there can be overlap in the timing and manifestations of these syndromes. Evaluation and diagnosis of GVHD are discussed separately. (See "Clinical manifestations, diagnosis, and grading of acute graft-versus-host disease".)
●Immunosuppression – Immunosuppressive therapy is needed to prevent or reduce GVHD-associated symptoms and organ toxicity. The resultant immunosuppression exacerbates risks for viral, bacterial, and fungal infection/reactivation.
The selection of GVHD prophylaxis/treatment regimens is influenced by comorbidities and institutional approach, as discussed separately. (See "Prevention of graft-versus-host disease" and "Treatment of acute graft-versus-host disease" and "Treatment of chronic graft-versus-host disease".)
Adverse effects — Allogeneic HCT is associated with significant and potentially life-altering AEs other than GVHD.
●Acute – The intensity of the conditioning regimen coupled with effects related to prior treatments cause profound and prolonged cytopenias and complications associated with anemia, infections, and bleeding. (See "Hematopoietic support after hematopoietic cell transplantation".)
Some patients experience other complications of the conditioning regimen, such as hepatic sinusoidal obstruction syndrome (SOS; also called veno-occlusive disease [VOD]) or other organ toxicity (eg, heart, lung, kidney). (See "Hepatic sinusoidal obstruction syndrome (veno-occlusive disease) in adults".)
Gastrointestinal and/or cutaneous manifestations of acute GVHD can begin soon after graft infusion. (See "Clinical manifestations, diagnosis, and grading of acute graft-versus-host disease".)
Reactivation of herpes simplex, varicella zoster, cytomegalovirus (CMV), Epstein-Barr virus (EBV), and other viruses can occur.
●Late/long term – Late complications of allogeneic HCT are also related to the underlying disease and its previous treatments; age, comorbidities, and other risk factors in the recipient; conditioning regimen; and chronic GVHD. Even when the underlying disease is controlled or cured, quality of life may be impaired after transplantation because of late AEs.
Common late AEs of allogeneic HCT may include infections and viral activation; skin and mucosal disruption; heart, lung, liver, and kidney complications; and second cancers. (See "Survival, quality of life, and late complications after hematopoietic cell transplantation in adults".)
In children, late AEs of allogeneic HCT can also include impaired growth and development, neurocognitive dysfunction, and other complications, as discussed separately. (See "Acute lymphoblastic leukemia/lymphoblastic lymphoma: Outcomes and late effects of treatment in children and adolescents".)
INDICATIONS —
The decision to proceed to allogeneic HCT must be individualized, with consideration of the status of the underlying disease, prior treatments, the balance of benefits and toxicities of transplantation compared with other available treatments, recipient age, comorbidities, individual risk factors for transplantation and its complications; and patient/family values and preferences. There are no universally accepted indications for allogeneic HCT nor for the optimal timing of transplantation, and practices vary.
For most diseases, no trials have randomly assigned patients to transplantation versus other treatments. As a result, decisions to choose allogeneic HCT versus an alternative approach are generally based on observational studies. For many conditions, the most persuasive data are from prospective studies that used "genetic randomization," in which patients are assigned to treatment based on the availability of a suitable allogeneic graft donor. As an example, studies of hematologic malignancies used allogeneic HCT for patients who had a human leukocyte antigen (HLA)-matched sibling donor (MSD) versus chemotherapy or autologous HCT for those without an MSD. It is difficult to compare results across studies because of differences in study eligibility, including age, disease status, and transplantation methods.
Similarly, few studies have examined the optimal timing of allogeneic HCT. The choice of timing is influenced by the underlying disease and its control or progression. For example, outcomes vary according to whether transplantation is performed when the patient is in complete remission (CR) or partial remission (PR) versus relapsed or refractory disease. The number and types of prior treatments, response to previous therapy, and current clinical status also have important effects on outcomes. For some disorders, it is beneficial to reduce the burden of disease prior to transplantation.
Details of indications for allogeneic HCT are described in disease-specific topics:
●Acute myeloid leukemia (AML) – (See "Acute myeloid leukemia in younger adults: Post-remission therapy", section on 'Myeloablative allogeneic transplantation' and "Treatment of relapsed or refractory acute myeloid leukemia", section on 'Hematopoietic cell transplantation'.)
●Acute lymphoblastic leukemia (ALL) – (See "Philadelphia chromosome-positive acute lymphoblastic leukemia in adults: Post-remission management" and "Philadelphia chromosome-negative acute lymphoblastic leukemia in adults: Post-remission management", section on 'Allogeneic transplantation' and "Treatment of relapsed or refractory acute lymphoblastic leukemia in adults".)
●Myelodysplastic syndromes/neoplasms (MDS) – (See "Myelodysplastic syndromes/neoplasms (MDS): Treatment of higher-risk MDS".)
●Myeloproliferative neoplasms (MPN) – (See "Myelofibrosis (MF): Management of primary MF and secondary MF", section on 'Transplant-eligible patients'.)
●Chronic lymphocytic leukemia (CLL) – (See "Hematopoietic cell transplantation in chronic lymphocytic leukemia".)
●Chronic myeloid leukemia (CML) – (See "Overview of the treatment of chronic myeloid leukemia".)
●Peripheral T cell lymphoma (PTCL) – (See "Treatment and prognosis of adult T cell leukemia-lymphoma", section on 'Hematopoietic cell transplantation' and "Treatment of relapsed or refractory peripheral T cell lymphoma".)
●Follicular lymphoma (FL) – (See "Treatment of relapsed or refractory follicular lymphoma", section on 'Consolidation with cellular therapy'.)
●Diffuse large B cell lymphoma (DLBCL) – (See "Diffuse large B cell lymphoma (DLBCL): Second or later relapse or patients who are medically unfit", section on 'Allogeneic hematopoietic cell transplantation'.)
●Nonhematologic malignancies – (See "Treatment and prognosis of neuroblastoma", section on 'High-risk disease'.)
●Nonmalignant inherited and acquired marrow disorders – (See "Hematopoietic stem cell transplantation and other curative therapies for transfusion-dependent thalassemia" and "Curative therapies in sickle cell disease including hematopoietic stem cell transplantation and gene therapy" and "Hematopoietic cell transplantation (HCT) for inherited bone marrow failure syndromes (IBMFS)", section on 'Introduction'.)
●Other – (See "Hematopoietic cell transplantation for severe combined immunodeficiencies" and "Chronic granulomatous disease: Treatment and prognosis" and "Paroxysmal nocturnal hemoglobinuria: Treatment and prognosis".)
ELIGIBILITY FOR ALLOGENEIC HCT —
Eligibility for allogeneic HCT varies with age, fitness, comorbidities, social supports, and institutional/national approach.
Eligibility is individualized and the decision should be made jointly by transplant specialists, other trusted clinicians, the patient, and loved ones (when appropriate).
The decision to pursue allogeneic HCT is informed by disease status (eg, stage, remission versus relapsed/refractory disease), cytogenetic/molecular features, and response to prior treatments. The decision should weigh potential benefits and toxicities of transplantation against those of other available treatments. Detailed analysis of the relative benefits and toxicity of allogeneic HCT and other management is discussed in disease-specific topics.
Allogeneic HCT requires the availability of a suitable donor. (See "Donor selection for hematopoietic cell transplantation".)
Eligibility criteria — There are no consensus criteria for allogeneic HCT, and the decision to pursue transplantation may vary among institutions and transplant specialists.
In general, patients are eligible for allogeneic HCT if they meet the following criteria (table 1):
●Disease is amenable to transplantation – Malignant and nonmalignant conditions that may benefit from allogeneic HCT are described above. (See 'Indications' above.)
●Age – There is no consensus upper age limit for allogeneic HCT, and age criteria vary among institutions.
Many centers limit myeloablative conditioning (MAC) allogeneic HCT to patients <55 years. Reduced-intensity conditioning (RIC) or nonmyeloablative conditioning (NMA) allogeneic HCT is often limited to patients <75 years of age.
●Performance status
•Adults – ECOG (Eastern Cooperative Oncology Group) performance status ≤2 or Karnofsky performance status (KPS) ≥70 (table 2) for MAC HCT, or KPS ≥50 for RIC/NMA HCT.
•Children – For patients <16 years, the Lansky Play-Performance Scale (LPPS) for Pediatric Functional Status can be used with similar cutoffs as the KPS [2].
●Organ function – Following are general guidelines for organ function:
•Kidney function – Serum creatinine <2 mg/dL (177 micromol/L) or creatinine clearance >50 mL/min. Transplantation of patients with more severe renal impairment is handled differently among transplant centers. Transplantation in patients on hemodialysis can be carried out at centers experienced with this support.
•Heart function – Left ventricular ejection fraction (LVEF) >35 percent.
•Lung function – Corrected diffusing capacity of the lungs for carbon monoxide (DLCO) >35 percent, but thresholds vary among centers.
•Liver function – Patients with frank cirrhosis of the liver are typically excluded from allogeneic HCT because of excessive mortality and morbidity.
The consequences of organ dysfunction are discussed below. (See 'Comorbidities' below.)
●Social supports – Adequate psychosocial and financial support are needed.
Allogeneic HCT creates substantial psychosocial and financial pressures. The patient's usual responsibilities are disrupted by prolonged hospitalization and frequent visits to the transplant center. Social contacts are diminished. Unhoused/homeless individuals are especially at risk; as an example, infectious risks associated with immunosuppression are increased by exposure to crowds of people. (See 'Social/economic factors' below.)
Patient evaluation — Pretransplant assessment must evaluate comorbidities that can impact outcomes. Our approach to pretransplant evaluation (table 3) follows, but details may vary among institutions.
Clinical
●History – While all elements of the patient's history are pertinent, issues relevant to potential complications include: performance status (table 2), psychologic history, prior therapies, transfusion history, drug allergies (especially to antibiotics), travel history, and a detailed infection history (especially a history of aspergillus infection or tuberculosis). (See "Evaluation for infection before hematopoietic cell transplantation", section on 'Recipient'.)
●Physical examination – The patient is evaluated for findings related to heart, lung, liver, and other organs.
Particular attention must be paid to the oral cavity, which is a potential source of infection. A dental examination and dental radiographs enable optimization of dental status prior to transplant.
Laboratory
●Hematology – Complete blood count with differential count.
●Chemistries – Complete metabolic panel, including electrolytes and kidney and liver function.
●Infectious – Hepatitis B, hepatitis C, herpes simplex, varicella, cytomegalovirus, Epstein-Barr virus, human T-lymphotropic virus types I and II.
Details of assessment for infectious agents prior to transplantation are presented separately. (See "Evaluation for infection before hematopoietic cell transplantation".)
Other testing
●Lungs – Chest radiograph, pulmonary function testing, including DLCO. (See "Overview of pulmonary function testing in adults".)
●Heart – Electrocardiogram, assessment of ejection fraction by echocardiogram or radionuclide ventriculogram. (See "Tests to evaluate left ventricular systolic function".)
Other studies are performed as clinically indicated.
Restaging — Staging prior to allogeneic HCT is informed by the underlying disease.
●Imaging – Patients with lymphoma usually undergo computed tomography (CT) scan and/or positron emission tomography (PET).
●Bone marrow – Patients with leukemia or lymphoma may undergo bone marrow examination to assess disease status.
●Neurologic – Head CT or magnetic resonance imaging (MRI) may be indicated to assess parenchymal involvement of the central nervous system. A lumbar puncture with cytologic examination is performed as clinically indicated to evaluate meningeal involvement. Patients with meningeal involvement usually require intrathecal chemotherapy and/or cranial radiation prior to transplantation.
CONSULTATION AND COUNSELING
Transplant consultation — Patients with a potential indication for allogeneic HCT should be offered the opportunity to discuss the procedure with a clinician who is part of an experienced transplantation team.
If allogeneic HCT is a consideration, the patient and primary relatives should undergo human leukocyte antigen (HLA) testing to assess their immune compatibility with the recipient. A database search is initiated to identify potential unrelated donors if no suitable match is found among relatives, or if transplantation must proceed promptly. (See "Donor selection for hematopoietic cell transplantation".)
Counseling
End-of-life and advance care planning — Advance care planning (ACP; eg, living will, power of attorney for health care, life-support instructions) should be completed while the patient is competent, to ensure that care is consistent with the patient's wishes. (See "Advance care planning and advance directives".)
A retrospective study of 602 patients who underwent allogeneic or autologous HCT (2011 to 2015) reported that >99 percent had ACP, but fewer than one-quarter had ACP documented in the outpatient setting [3]. An earlier study reported that one-half of 343 patients undergoing HCT had documented ACP and the absence of ACP was associated with inferior outcomes [4].
Fertility preservation — Patients with childbearing potential should receive counseling about the potential effect of treatment on fertility and options for fertility-preserving measures. (See "Fertility and reproductive hormone preservation: Overview of care prior to gonadotoxic therapy or surgery".)
Patient expectations — Informed consent guidelines mandate that patients have an accurate understanding of the risks of HCT.
Pretransplant expectations of outcomes by patients and clinicians were most concordant and accurate when outcomes were most likely to be favorable [5]. Among patients undergoing allogeneic HCT with an unrelated donor graft (in which one-year treatment-related mortality [TRM] was 44 to 67 percent), physicians estimated 38 to 55 percent one-year TRM, while patients estimated 15 to 19 percent one-year TRM. By contrast, for patients undergoing autologous HCT (in which one-year TRM was 10 percent), patient and physician estimates were 12 and 10 percent, respectively.
PROGNOSTIC FACTORS —
Outcomes are associated with both clinical and disease-related features.
In general, superior outcomes are associated with younger age, disease in remission or responsive to therapy, absence of active infections or other significant comorbidities, availability of a human leukocyte antigen (HLA)-matched donor, and good socioeconomic support (table 4) [6]. Conversely, increased morbidity and/or mortality are associated with older age, relapsed or refractory disease, history of aggressive chemotherapy, and comorbidities.
Age — Age may influence the choice of conditioning regimen and/or other aspects of transplantation, but there is no clear evidence that age is an independent risk factor for mortality. The role of age in selecting conditioning therapy is discussed above. (See 'Conditioning therapy' above.)
Aging is associated with declines in organ function. As an example, age is associated with decreased glomerular filtration rate, and it is a risk factor for the development of chronic kidney disease after allogeneic HCT [7,8]. The pharmacokinetics of immunosuppressives (eg, cyclosporine) change with age [9]. Similarly, decreased lung function might interfere with airway clearance and infection prevention after HCT.
The median age of patients undergoing allogeneic HCT has increased due, in part, to the availability of less toxic conditioning regimens [10]. As an example, the median age at transplantation was 25, 39, and 46 years in the 1980s, 1990s, and 2000s, respectively, according to the CIBMTR (Center for International Blood and Marrow Transplantation Research) database [11]. In another CIBMTR study, 46 percent of patients undergoing allogeneic HCT were 40 to 64 years, and 29 percent were ≥65 years [12].
●Compared with patients ≥65 years, patients 60 to 64 years had better outcomes with allogeneic HCT for acute myeloid leukemia (AML) in first complete remission (CR1; 2007 to 2017) in a CIBMTR study of 1321 patients [13]. Patients 65 to 69 years had inferior overall survival (OS; hazard ratio [HR] for death 1.27 [95% CI 1.09-1.49]) and increased nonrelapse mortality (NRM; HR 1.34 [95% CI 1.06-1.69]) compared with patients 60 to 64 years. Age-associated differences in OS and NRM persisted after accounting for other risk factors.
●There was no association between age and NRM or relapse rate in a retrospective EBMT (European Bone Marrow Transplantation) study of 1333 adults (50 to 74 years) undergoing allogeneic HCT for myelodysplastic syndromes/neoplasms (MDS) [14]. By contrast, NRM was greater in patients with advanced-stage disease, unrelated donor grafts, and myeloablative conditioning (MAC).
●Age was not independently associated with survival outcomes or graft-versus-host disease (GVHD) among 372 patients (60 to 75 years) enrolled in prospective studies of nonmyeloablative conditioning (NMA) allogeneic HCT for hematologic malignancies [15]. Increased age was not associated with differences in five-year OS (35 percent), progression-free survival (PFS; 32 percent), NRM (27 percent), or relapse (41 percent), but there was an association of increased age with bacterial infections and hospitalizations.
Comorbidities — Pretransplant organ dysfunction is associated with increased transplant-related complications.
●Lungs – Pre-existent lung disease is associated with inferior transplant outcomes.
Historically, a corrected diffusing capacity of the lungs for carbon monoxide (DLCO) of ≥60 percent was required for allogeneic HCT eligibility but selected patients with DLCO <60 percent can be transplanted successfully [16].
Patients with known pulmonary dysfunction should avoid conditioning regimens that are known to decrease diffusing capacity, such as BCNU-based regimens or busulfan plus total body irradiation; this is particularly important for patients with autoimmune diseases involving the lungs. (See "Pulmonary toxicity associated with chemotherapy and other cytotoxic agents".)
●Heart – Life-threatening cardiac complications are uncommon following allogeneic HCT, but transplantation can cause subacute cardiac injury even in patients with normal pretransplant cardiac function. Cardiac injury is likely to have a greater impact in patients with less cardiac reserve.
Reduced left ventricular ejection fraction (LVEF) and a history of heart failure are strongly associated with cardiac toxicity following transplantation. Smoking, obesity, hyperlipidemia, hypertension, and hyperglycemia should be corrected or minimized, if possible, prior to transplant. In general, patients with LVEF <35 percent, uncontrolled coronary artery disease, or uncontrolled arrhythmias are not considered candidates for allogeneic HCT.
●Liver – Abnormal liver function tests (LFTs) are common in patients with hematologic malignancies.
Potential causes of liver dysfunction include hepatitis, alcohol overuse, hepatic steatosis, iron overload from repeated transfusions, and other conditions. The etiology should be evaluated in patients with abnormal LFTs, ideally in consultation with a hepatologist.
There is increased risk for hepatic sinusoidal obstructive syndrome (SOS; also called veno-occlusive disease) as a complication of HCT in patients with elevated serum transaminases, prior history of SOS, exposure to gemtuzumab ozogamicin or other antibody-drug conjugates, and other conditions. (See "Hepatic sinusoidal obstruction syndrome (veno-occlusive disease) in adults".)
●Kidneys – Renal dysfunction increases the risk of transplant-related adverse effects in patients undergoing allogeneic HCT.
Most clinical trials have required serum creatinine <2 mg/dL (177 micromol/L) or creatinine clearance >50 to 60 mL/min for enrollment.
Patients are exposed to many nephrotoxic agents after allogeneic HCT, including cyclosporine, tacrolimus, aminoglycosides, and amphotericin. Patients with reduced kidney function may require dose modification of many agents and/or conditioning regimen (eg, reduction of melphalan dose). (See "Preparative regimens for hematopoietic cell transplantation".)
Infectious diseases — Bacterial, fungal, and viral infections are common complications of allogeneic HCT. Pretransplant viral infections influence transplant management.
Seropositivity for human immunodeficiency virus (HIV), hepatitis B, or hepatitis C does not necessarily exclude patients from eligibility for allogeneic HCT, but it does affect transplant care. Patients with hepatitis B or hepatitis C are at increased risk of viral reactivation after transplant, even if the infection appears to be resolved. (See "Hepatitis B virus reactivation associated with immunosuppressive therapy" and "HIV-related lymphomas: Treatment of systemic lymphoma", section on 'Allogeneic transplantation'.)
The status of these viral infections should be evaluated prior to transplantation, ideally in consultation with an infectious disease expert, as discussed separately. (See "Evaluation for infection before hematopoietic cell transplantation".)
Weight/nutritional status — Extremes of body weight can affect transplant management but are not proven to be associated with inferior outcomes.
Unless obesity is extreme, it does not exclude a patient from eligibility for allogeneic HCT. However, excess patient weight may affect drug delivery/dosing and make airway clearance and skin care more challenging. All patients with obesity, anorexia, cachexia, or malnutrition should be evaluated by a dietician to optimize their nutritional regimen before and during the transplant procedure.
Impaired nutritional status and sarcopenia may contribute to excessive NRM in patients undergoing allogeneic HCT. A study of 182 patients undergoing allogeneic HCT for acute leukemia reported that substantial loss of body weight (LBW) before transplantation was associated with inferior outcomes [17]. Compared with lesser amounts of LBW, patients with ≥13.2 percent LBW between diagnosis or relapse and transplantation had inferior two-year OS (39.9 versus 65.8 percent) and increased NRM (36.1 versus 11.5 percent). In a study that included 125 patients undergoing transplantation, sarcopenia (judged by CT) was associated with increased NRM [18].
Social/economic factors — Access to allogeneic transplantation is influenced by various sociocultural and economic factors. There is limited evidence that race/ethnicity and socioeconomic status are associated with inferior transplant outcomes, but the interactions are complex and the causes are not clear.
●Access to allogeneic HCT – Utilization of transplantation may be associated with age, sex, race/ethnicity, insurance coverage, and socioeconomic status; the influence of marital status, language barriers, distance from a transplant center, and caregiver availability are less defined [19,20].
Race and ethnicity are particularly relevant when analyzing access to allogeneic HCT. Racial disparities that are routinely observed with access to health care may be accentuated with transplantation because of the complexity and expense of the procedure and limited availability. White donors of European ancestry are overrepresented in unrelated donor registries, and White patients are more likely than Black patients to find a well-matched unrelated donor [21-23].
Sociodemographic barriers to transplantation are more challenging to define and are not reliably captured at the level of an individual patient. Most studies have focused on population-level indicators to define disparities (eg, median household income based on zip code of residence). A study of 1102 patients who received a consultation for HCT reported that non-Hispanic White patients were more likely than Hispanic, non-Hispanic Black, and others to proceed to HCT [24]. Even if well-insured, allogeneic HCT may incur major out-of-pocket expenses. Compared with patients covered by private insurance in the United States, patients insured by Medicare or Medicaid, or who were uninsured were less likely to undergo transplantation [25].
●Transplant outcomes – Compared with White patients, Black patients who undergo allogeneic HCT may have inferior outcomes.
The reasons for differences in outcomes between racial/ethnic groups are uncertain. This may be related to higher rates of comorbid conditions; for example, hypertension and kidney disease are more prevalent in the American Black population. Management can be affected because some clinicians have difficulty interpreting cutaneous GVHD in patients with a darker skin complexion.
Examples of studies that include outcomes according to race and/or ethnicity include:
•Among 2221 allogeneic HCT recipients, Black Americans had inferior outcomes compared with White American patients [26]. Black patients had higher mortality rates (HR 1.71 [95% CI 1.25-2.34]) even after controlling for donor type, pretransplantation risk category, age, donor/patient sex, and cytomegalovirus exposure. Black patients also had higher rates of NRM and acute GVHD.
•Black Americans had inferior outcomes compared with White Americans in a study of 6207 patients undergoing unrelated allogeneic HCT [27]. Black patients had increased rates of overall mortality (HR 1.71 [95% CI 1.25-2.35]), NRM (HR 1.74 [95% CI 1.20-2.54]), and relapse mortality (HR 2.03 [95% CI 1.12-3.65]). Socioeconomic indicators did not differ between Black and White patients.
Disease-related — Disease-related factors vary according to the underlying disease.
For malignancies, transplant outcomes are related to the disease, stage, status (eg, remission versus active or relapsed disease), and certain cytogenetic abnormalities. For many malignancies, rates of relapse and GVHD are influenced by the nature and intensity of the conditioning regimen [28-30]. Prevention of relapse after allogeneic HCT depends importantly on the graft-versus-tumor (GVT) effect; like GVHD, GVT depends on a degree of immunologic mismatch between the donor and the recipient, with the result that rates of GVHD and relapse are often inversely related. Risk factors for different malignancies are described in disease-specific topics.
For nonmalignant conditions, disease-related factors are described in specific topics.
PROGNOSTIC INSTRUMENTS —
Various prognostic instruments assist in estimating outcomes in patients undergoing allogeneic HCT, but no single instrument has proven superior. While most tools effectively stratify risk among patient populations, they are suboptimal for accurately predicting outcomes for a given individual.
In general, prognostic instruments use either patient characteristics (eg, comorbidity profile, age), donor immunologic match, disease features (ie, remission/relapse status, response to therapy), laboratory findings, or combinations of these factors to estimate prognosis. Most can accurately stratify risk for survival outcomes, but they are generally not effective for predicting who will develop chronic graft-versus-host disease (GVHD).
The preferred prognostic model varies among institutions. The EBMT (European Bone Marrow Transplantation) score [31] and the HCT-CI (Hematopoietic Cell Transplantation-Specific Comorbidity Index) [31-33] are most widely used, but others are acceptable. Details of various prognostic instruments are presented in the sections that follow.
Contemporary prognostic instruments effectively distinguish transplant outcomes in populations of patients, but they remain suboptimal for accurately predicting outcomes for an individual. Few studies have systematically compared the accuracy of various prognostic tools. In a single-center study of 528 adults undergoing allogeneic HCT (2011 to 2015), eight prognostic instruments displayed variable accuracy for predicting survival, but performance differed according to the outcomes measured, and the accuracy of some instruments varied with the intensity of the consolidation regimen [34]. Other studies have compared the performance of two or three different prognostic instruments [35-42].
Importantly, mortality rates have declined since the development of most prognostic instruments [43,44]. As a result, the application of these tools may suggest inferior outcomes compared with contemporary practice. Improved transplant outcomes are attributable to better patient selection, supportive care, conditioning regimens, graft selection, and GVHD prophylaxis and treatment.
Studies that reported improving outcomes with allogeneic HCT include:
●Improved survival and fewer complications were reported in 1131 patients undergoing first allogeneic HCT in 2013 through 2017, compared with 1148 patients transplanted in 2003 through 2007, in a single-center study [45]. Rates of day-200 overall mortality (hazard ratio [HR] 0.66 [95% CI 0.56-0.78]), nonrelapse mortality (NRM; HR 0.66 [95% CI 0.48-0.89]), and cancer relapses (HR 0.76 [95% CI 0.61-0.94]) decreased in the 2013 to 2017 cohort, compared with the earlier patients. Improved mortality rates were reported for patients who underwent myeloablative conditioning (MAC) versus reduced-intensity conditioning (RIC), and for a matched sibling donor (MSD) versus an unrelated donor. There were also reductions in the rates of acute GVHD, chronic GVHD, jaundice, kidney insufficiency, mechanical ventilation, high-level cytomegalovirus (CMV) viremia, gram-negative bacteremia, and invasive mold infections. An earlier study from the same institution also reported improved outcomes in 2003 through 2007 compared with 1993 through 1997 [43].
●A study of 5972 patients <50 years undergoing MAC allogeneic HCT for acute myeloid leukemia (AML) in first or second complete remission (CR) reported improved rates of treatment-related mortality (TRM) in 2000 through 2004 compared with 1985 through 1989 [44].
EBMT score — The EBMT (European Bone Marrow Transplantation) risk score is a simple tool that uses five clinical parameters (age, disease stage, time from diagnosis, donor type, and donor-recipient sex match) to estimate prognosis [31].
The EBMT score is simple to calculate (table 5), and the resultant score can range from 0 to 7 [46]. Note that definitions for disease stage (ie, early, intermediate, late) vary according to the disease.
The EBMT risk score was developed using five-year overall survival (OS) and TRM data from 3142 patients with chronic myeloid leukemia (CML) who underwent allogeneic HCT [31]. The EBMT risk score model was subsequently validated in the following clinical settings:
●CML, using separate data from the International Bone Marrow Transplant Registry [47]
●Acute leukemias (AML and acute lymphoblastic leukemia [ALL]), which correlated with day-100 mortality and two-year OS, leukemia-free survival (LFS), and NRM, using data from GITMO (the Italian national transplantation network) [48]
●Various hematologic disorders (ie, CML, AML, ALL, myelodysplastic syndromes/neoplasms [MDS], multiple myeloma, non-Hodgkin lymphoma, aplastic anemia), which predicted survival, TRM, and death from relapse [49]
HCT-CI score — The HCT-CI (Hematopoietic Cell Transplantation-Specific Comorbidity Index) classifies risk based on 17 patient features, including organ dysfunction (lungs, heart, liver, kidney), other comorbidities (eg, diabetes, cerebrovascular disease), and prior treatment for a solid tumor.
An online calculator is available for determining the HCT-CI score (table 6). The HCT-CI score can range from 0 to 29 [32].
HCT-CI was developed using NRM data from 708 consecutive allogeneic transplants at a single institution and validated using data from an independent group of 346 patients [32]. Patients with HCT-CI scores of 0, 1, 2, 3, and ≥4 had two-year NRM rates of 14, 22, 19, 41, and 40 percent, respectively. Validation of the HCT-CI risk score in this and other settings indicates the importance of comorbidities in assessing suitability for HCT [50]. The focus of HCT-CI on comorbidities contrasts with the EBMT risk score, which is based on disease features. (See 'EBMT score' above.)
A variant model, the HCT-CI/age composite score, combines age and comorbidities to predict transplant outcomes [51]. An online calculator is available to determine the HCT-CI/age composite score. In this model, age >40 years has a similar weight as a single additional comorbidity (eg, diabetes requiring pharmacologic intervention).
HCT-CI has been validated in other settings:
●HCT-CI was associated with NRM and OS in a prospective study of 8115 patients undergoing allogeneic HCT and 11,652 patients undergoing autologous HCT in the CIBMTR (Center for International Blood and Marrow Transplant Research) registry [35].
●HCT-CI was associated with mortality with acute GVHD in 2985 patients receiving human leukocyte antigen (HLA)-matched grafts for hematologic malignancies or nonmalignant disorders [52].
●HCT-CI predicted OS and NRM in 252 children undergoing first allogeneic HCT for malignant or nonmalignant diseases [53].
●When patients were stratified according to low- versus high-risk disease, HCT-CI accurately predicted similar rates of two-year OS in adults transplanted for AML (391 patients) and MDS (186 patients), whether they received MAC or nonmyeloablative conditioning (NMA) allogeneic HCT [54].
●Outcomes correlated with HCT-CI score in 372 patients (60 to 75 years) undergoing NMA allogeneic HCT for hematologic malignancies; compared with HCT-CI score 0, survival was inferior for patients with HCT-CI score 1 to 2 (HR 1.58 [95% CI 1.08-2.31]) and for HCT-CI score ≥3 (HR 1.97 [95% CI 1.38-2.80]) [15].
●HCT-CI accurately predicted two-year OS and NRM according to risk score (ie, score 0, 1 to 2, ≥3) in a prospective, multicenter study of 1937 adults undergoing HCT for malignant (eg, lymphoma, MDS, AML) or nonmalignant hematologic diseases [55].
●Inferior OS was associated with HCT-CI score ≥4 in 129 patients undergoing allogeneic HCT for chronic myelomonocytic leukemia (CMML) [56].
Other models — In addition to the EBMT and HCT-CI scores (described above), we consider the following prognostic models acceptable.
Comorbidity-EBMT index — The Comorbidity-EBMT index combines comorbidity-specific information (from the HCT-CI) with the factors included in the EBMT score [36].
rPAM — The revised PAM (rPAM; Pretransplant Assessment of Mortality) score is not often used to assess prognosis. This model is based on age, donor type, disease risk, conditioning regimen, and patient and donor CMV serology [57].
The rPAM score was derived from an earlier model (PAM) that did not include CMV status; instead, PAM included serum creatinine, serum alanine aminotransferase, FEV1 (forced expiratory volume in one second), and carbon monoxide diffusing capacity of the lung [58]. The rPAM and PAM scores use actual laboratory values to represent organ function instead of a score based on patient narratives, as in HCT-CI.
The rPAM score was validated using mortality, relapse, and NRM data from 429 patients who underwent allogeneic HCT for myeloid or lymphoid malignancies or bone marrow failure [57]. The original PAM score was validated using survival data from 544 patients who underwent allogeneic HCT for AML in a single-center study [59].
rDRI — The rDRI (refined Disease Risk Index) predicts transplant outcomes based on the type and stage of disease. The rDRI can be applied to various hematologic malignancies, disease stages, and transplant techniques, including the intensity of the conditioning regimen.
The rDFI stratifies patients into one of four risk categories (ie, low, intermediate, high, and very high risk) that are based on the underlying disease and stage (determined by status of remission/relapse, response to prior therapy, and cytogenetic features) [60]. Disease stage is defined differently for each disease, as indicated in the accompanying table (table 7). The rDRI was developed after application of an earlier version of the instrument (DRI) to a large population of patients in the CIBMTR database [60].
Transplant outcomes are distinctly different among the four rDRI risk categories. When the rDRI was applied to 13,131 patients in the CIBMTR database, the low-, intermediate-, high-, and very high-risk categories were associated with 66, 51, 33, and 23 percent two-year OS, respectively [60]. The original DRI model was effective for estimating four-year OS, progression-free survival, relapse, and NRM among 718 patients undergoing allogeneic HCT [61].
EASIX — The EASIX (Endothelial Activation and Stress Index) score is a biomarker-only prognostic model that uses three routine laboratory studies: serum creatinine, lactate dehydrogenase (LDH), and platelet count [62,63].
The EASIX score is calculated as follows: LDH (units/L) x creatinine (mg/dL)/platelets/nanoL.
EASIX was accurate for the prediction of mortality and for transplant-associated microangiopathy after allogeneic HCT in a population of >2000 patients from five different institutions; the prognostic value of EASIX was independent of HCT-CI and EBMT scores [63]. EASIX was also effective for predicting outcomes in patients undergoing allogeneic HCT for thalassemia major [64], myelofibrosis [65], and in patients receiving an umbilical cord blood graft [66].
INFORMATION FOR PATIENTS —
UpToDate offers two types of patient education materials, "The Basics" and "Beyond the Basics." The Basics patient education pieces are written in plain language, at the 5th to 6th grade reading level, and they answer the four or five key questions a patient might have about a given condition. These articles are best for patients who want a general overview and who prefer short, easy-to-read materials. Beyond the Basics patient education pieces are longer, more sophisticated, and more detailed. These articles are written at the 10th to 12th grade reading level and are best for patients who want in-depth information and are comfortable with some medical jargon.
Here are the patient education articles that are relevant to this topic. We encourage you to print or e-mail these topics to your patients. (You can also locate patient education articles on a variety of subjects by searching on "patient education" and the keyword(s) of interest.)
●Basics topics (see "Patient education: Allogeneic bone marrow transplant (The Basics)")
SUMMARY
●Description – Allogeneic hematopoietic cell transplantation (HCT) is used to treat various malignancies, nonmalignant marrow disorders, inherited/germline hematologic or metabolic disorders, and other conditions.
●Overview – Allogeneic HCT involves treatment with a conditioning regimen (chemotherapy, radiation therapy, and/or immunotherapy) to reduce the burden of diseased bone marrow cells, followed by an infusion of an allogeneic hematopoietic graft. Key features include:
•Graft – Bone marrow, peripheral blood, or umbilical cord blood from an immunologically compatible related or unrelated donor. (See 'Graft selection' above.)
•Conditioning therapy – The choice of myeloablative versus nonmyeloablative or reduced-intensity conditioning is informed by age, comorbidities, underlying disease, and institutional approach. (See 'Conditioning therapy' above.)
•Toxicity – Morbidity and potential mortality are related to cytopenias, complications from the conditioning regimen, graft-versus-host disease (GVHD), immunosuppression to prevent and treat GVHD, and other aspects of transplantation. (See 'Toxicity' above.)
●Indications – The decision to pursue transplantation is individualized, with consideration of the underlying disease and its status; prior treatments; the balance of benefits and toxicity compared with other available treatments; age; comorbidities; risk factors for transplant-related complications; and patient/family preferences. (See 'Indications' above.)
●Eligibility – In general, patients should have a disease amenable to transplantation, adequate performance status, good organ function (eg, heart, lungs, kidneys, liver), adequate social supports, and a suitable graft donor (table 1). (See 'Eligibility criteria' above.)
●Evaluation – History, physical examination, and laboratory studies assess comorbidities and status of the underlying disease. (See 'Eligibility for allogeneic HCT' above.)
●Consultation – The patient should be referred to transplant specialists to assess eligibility and initiate a donor search. (See 'Transplant consultation' above.)
●Counseling – Potential outcomes, end-of-life considerations, and fertility preservation (if appropriate) are discussed. (See 'Counseling' above.)
●Prognostic factors – Outcomes are influenced by disease- and patient-related features. (See 'Prognostic factors' above.)
•Disease-related – Disease stage, status (eg, remission versus active), response to prior therapy, and certain cytogenetic features. (See 'Disease-related' above.)
•Patient-related – Age, fitness, comorbidities, nutritional status, and social supports.
●Prognostic instruments – No prognostic instrument has proven superior, and the preferred tool varies among institutions. (See 'Prognostic instruments' above.)
These instruments effectively stratify risk among populations but are less successful for predicting individual patient outcomes.
The most commonly used models:
•EBMT – EBMT (European Group for Blood and Marrow Transplantation) risk score uses five clinical parameters (age, disease stage, time from diagnosis, donor type, and donor-recipient sex match) (table 5). (See 'EBMT score' above.)
•HCT-CI – HCT-CI (Hematopoietic Cell Transplantation-Specific Comorbidity Index) classifies risk with 17 patient-related features (lung, heart, liver, kidney dysfunction), diabetes, cerebrovascular disease, other comorbidities, and prior treatment for solid tumor with an online calculator (table 6). (See 'HCT-CI score' above.)
Other instruments:
-Comorbidity-EBMT index – Combines HCT-CI comorbidity information with aspects of the EBMT model. (See 'Comorbidity-EBMT index' above.)
-rPAM – Revised Pretransplant Assessment of Mortality score uses age, donor type, disease risk, conditioning regimen, and cytomegalovirus serology. (See 'rPAM' above.)
-rDRI – Refined Disease Risk Index predicts outcomes based on the type and stage of disease (table 7). (See 'rDRI' above.)
-EASIX – EASIX (Endothelial Activation and Stress Index) is a biomarker-only model based on serum creatinine, lactate dehydrogenase, and platelet count. (See 'EASIX' above.)
