ﺑﺎﺯﮔﺸﺖ ﺑﻪ ﺻﻔﺤﻪ ﻗﺒﻠﯽ
خرید پکیج
تعداد آیتم قابل مشاهده باقیمانده : 3 مورد
نسخه الکترونیک
medimedia.ir

Chlorambucil: Drug information

Chlorambucil: Drug information
(For additional information see "Chlorambucil: Patient drug information" and see "Chlorambucil: Pediatric drug information")

For abbreviations, symbols, and age group definitions used in Lexicomp (show table)
ALERT: US Boxed Warning
Bone marrow suppression:

Chlorambucil can severely suppress bone marrow function.

Adverse effects:

Chlorambucil is a carcinogen in humans. Chlorambucil is probably mutagenic and teratogenic in humans. Chlorambucil produces human infertility.

Brand Names: US
  • Leukeran
Brand Names: Canada
  • Leukeran
Pharmacologic Category
  • Antineoplastic Agent, Alkylating Agent;
  • Antineoplastic Agent, Alkylating Agent (Nitrogen Mustard)
Dosing: Adult

Note: Reduce initial dose if full-dose radiation or myelotoxic drugs have been administered within the last month. With bone marrow lymphocytic infiltration involvement (in chronic lymphocytic leukemia [CLL], Hodgkin lymphoma, or non-Hodgkin lymphoma [NHL]), the manufacturer recommends a maximum dose of 0.1 mg/kg/day; while short treatment courses are preferred, if maintenance therapy is required, the manufacturer recommends a maximum dose of 0.1 mg/kg/day.

Chronic lymphocytic leukemia

Chronic lymphocytic leukemia: Oral:

Chronic lymphocytic leukemia in previously untreated patients (off-label dosing): 0.4 mg/kg day 1 every 2 weeks; if tolerated may increase by 0.1 mg/kg with each treatment course to a maximum dose of 0.8 mg/kg and maximum of 24 cycles (Eichhorst 2009) or 0.5 mg/kg on days 1 and 15 every 28 days for 6 cycles (Goede 2014) or 30 mg/m2 day 1 every 2 weeks (in combination with prednisone) (Raphael 1991) or 40 mg/m2 day 1 every 4 weeks until disease progression or complete remission or response plateau for up to a maximum of 12 cycles (Rai 2000).

Chronic lymphocytic leukemia in previously untreated patients (off-label combinations):

Chlorambucil-obinutuzumab: 0.5 mg/kg on days 1 and 15 every 28 days for 6 cycles (Goede 2014).

Chlorambucil-ofatumumab: 10 mg/m2 once daily for 7 days (days 1 to 7) every 28 days for a minimum of 3 cycles and up to 12 cycles or best response (clinical response that did not improve after 3 additional cycles); if necessary, reduce dose to 7.5 mg/m2/day and then to 5 mg/m2/day for hematologic toxicity (Hillmen 2015).

Chlorambucil-rituximab: 10 mg/m2 once daily for 7 days (days 1 to 7) every 28 days for 6 to 12 cycles (Hillmen 2014).

Manufacturer’s labeling: 0.1 mg/kg/day for 3 to 6 weeks or 0.4 mg/kg pulsed doses administered intermittently, biweekly, or monthly (increased by 0.1 mg/kg/dose until response/toxicity observed).

Hodgkin lymphoma

Hodgkin lymphoma: Oral : ChlVPP regimen: 6 mg/m2 once daily (maximum 10 mg/day) on days 1 to 14 every 28 days (in combination with vinblastine, procarbazine, and prednisolone) until complete remission plus 2 cycles (Selby 1990) or 6 mg/m2 once daily on days 1 to 14 every 28 days (in combination with vinblastine, procarbazine, and prednisone) for 6 cycles (Vose 1991).

Idiopathic membranous nephropathy

Idiopathic membranous nephropathy (alternative agent) (off-label use): Oral: 0.15 to 0.2 mg/kg/day during months 2, 4, and 6 (alternating with prednisolone/methylprednisolone during months 1, 3, and 5) (Howman 2013; KDIGO 2012). Note: Due to potential adverse events, other agents may be preferred over chlorambucil.

Necrobiotic xanthogranuloma

Necrobiotic xanthogranuloma (off-label use; based on limited data): Oral: 2 to 4 mg once daily either with or without systemic corticosteroids (Finan 1986; Hilal 2018; Mehregan 1992; Miguel 2017) or 10 mg once daily for 14 days of a 28-day treatment cycle for 8 cycles (Ryan 2012) or 10 mg once daily, reduced to 2 mg once daily (in combination with prednisone) (Wells 2004).

Non-Hodgkin lymphomas

Non-Hodgkin lymphomas: Oral:

Follicular lymphoma (off-label dosing): 6 mg/m2 once daily during weeks 1 to 6, followed 8 weeks later (if response occurred) by 6 mg/m2 once daily for 2 weeks of a 4-week cycle for 4 cycles (in combination with rituximab) (Martinelli 2003; Martinelli 2015).

Mucosa-associated lymphoid tissue lymphoma (off-label dosing): 6 mg/m2 once daily during weeks 1 to 6, followed by 6 mg/m2 once daily for 2 weeks of a 4-week cycle for up to 4 cycles (in combination with rituximab) (Zucca 2017).

Manufacturer’s labeling: 0.1 mg/kg/day for 3 to 6 weeks.

Waldenström macroglobulinemia

Waldenström macroglobulinemia (alternative agent) (off-label use): Oral: 8 mg/m2 (6 mg/m2 in patients >75 years of age) once daily for 10 days every 28 days for up to 12 cycles (Leblond 2013) or 0.1 mg/kg/day (continuously) for at least 6 months (Kyle 2000) or 0.3 mg/kg/day for 7 days every 6 weeks for at least 6 months (Kyle 2000).

Dosage adjustment for concomitant therapy: Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult drug interactions database for more information.

Dosing: Kidney Impairment: Adult

There are no dosage adjustments provided in the manufacturer's labeling; however, renal elimination of unchanged chlorambucil and active metabolite (phenylacetic acid mustard) is minimal and renal impairment is not likely to affect elimination. The following adjustments have been recommended:

Aronoff 2007:

CrCl >50 mL/minute: No adjustment necessary.

CrCl 10 to 50 mL/minute: Administer 75% of dose.

CrCl <10 mL/minute: Administer 50% of dose.

Peritoneal dialysis (PD): Administer 50% of dose.

Kintzel 1995: Based on the pharmacokinetics, dosage adjustment is not indicated.

Idiopathic membranous nephropathy (off-label use): Serum creatinine >2 mg/dL: Maximum daily dose: 0.1 mg/kg/day (KDIGO 2012).

Dosing: Hepatic Impairment: Adult

Chlorambucil undergoes extensive hepatic metabolism. Although dosage reduction should be considered in patients with hepatic impairment, there are no dosage adjustments provided in the manufacturer's labeling (data is insufficient).

Dosing: Obesity: Adult

American Society of Clinical Oncology guidelines for appropriate systemic therapy dosing in adults with cancer with a BMI ≥30 kg/m2 : Utilize patient's actual body weight for calculation of BSA- or weight-based dosing; manage regimen-related toxicities in the same manner as for patients with a BMI <30 kg/m2; if a dose reduction is utilized due to toxicity, may consider resumption of full, weight-based dosing (or previously tolerated dose level) with subsequent cycles only if dose escalations are allowed in the prescribing information, if contributing underlying factors (eg, hepatic or kidney impairment) are sufficiently resolved, AND if performance status has markedly improved or is considered adequate (ASCO [Griggs 2021]). Note: Some treatment regimens or conditions have maximum dosage recommendations (refer to "Dosing: Adult" for maximum dose limitations).

Dosing: Adjustment for Toxicity: Adult

Skin reactions: Discontinue treatment

Hematologic:

WBC or platelets below normal: Reduce dose.

Severely depressed WBC or platelet counts: Discontinue.

Persistently low neutrophil or platelet counts or peripheral lymphocytosis: May be suggestive of bone marrow infiltration; if infiltration confirmed, do not exceed 0.1 mg/kg/day.

Concurrent or within 4 weeks (before or after) of chemotherapy/radiotherapy: Initiate treatment cautiously; reduce dose; monitor closely.

Dosing: Older Adult

Refer to adult dosing. Begin at the lower end of dosing range(s)

Dosing: Pediatric

(For additional information see "Chlorambucil: Pediatric drug information")

Note: For oncologic uses, dosing and frequency may vary by protocol and/or treatment phase; refer to specific protocol.

Hodgkin lymphoma

Hodgkin lymphoma: Limited data available: Infants ≥7 months, Children, and Adolescents: ChlVPP regimen: Oral: 6 mg/m2/day on days 1 to 14 of a 28-day cycle for 6 to 10 cycles in combination with vinblastine, procarbazine, and prednisolone (Atra 2002; Capra 2007; Hall 2007; Stoneham 2007)

Nephrotic syndrome; frequently relapsing steroid-sensitive

Nephrotic syndrome; frequently relapsing steroid-sensitive: Limited data available: Children and Adolescents: Oral: 0.1 to 0.2 mg/kg/day once daily for 8 weeks (maximum cumulative dose: 11.2 mg/kg) (Baluarte 1978; Hodson 2010; KDIGO 2012); Note: Chlorambucil is not a preferred agent due to a higher incidence of adverse effects with no greater efficacy (Gipson 2009).

Dosage adjustment for concomitant therapy: Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult drug interactions database for more information.

Dosing adjustment for toxicity: The presented dosing adjustments are based on experience in adult patients; specific recommendations for pediatric patients are limited. Refer to specific protocol for management.

Adult:

Skin reactions: Discontinue treatment

Hematologic:

WBC or platelets below normal: Reduce dose

Severely depressed WBC or platelet counts: Discontinue

Persistently low neutrophil or platelet counts or peripheral lymphocytosis: May be suggestive of bone marrow infiltration; if infiltration confirmed, do not exceed 0.1 mg/kg/day in adults

Concurrent or within 4 weeks (before or after) of chemotherapy/radiotherapy: Initiate treatment cautiously; reduce dose; monitor closely.

Dosing: Kidney Impairment: Pediatric

There are no dosage adjustments provided in manufacturer's labeling; however, based on experience in adult patients, renal elimination of unchanged chlorambucil and active metabolite (phenylacetic acid mustard) is minimal and renal impairment is not likely to affect elimination.

Dosing: Hepatic Impairment: Pediatric

Chlorambucil undergoes extensive hepatic metabolism. Although dosage reduction should be considered in patients with hepatic impairment, there are no dosage adjustments provided in the manufacturer's labeling (data is insufficient).

Adverse Reactions

The following adverse drug reactions and incidences are derived from product labeling unless otherwise specified.

Frequency not defined.

Central nervous system: Drug fever, peripheral neuropathy

Dermatologic: Allergic skin reaction, skin rash, urticaria

Endocrine & metabolic: Amenorrhea

Gastrointestinal: Diarrhea (infrequent), nausea (infrequent), oral mucosa ulcer (infrequent), vomiting (infrequent)

Genitourinary: Azoospermia, cystitis (sterile), infertility

Hematologic & oncologic: Anemia, bone marrow depression, bone marrow failure (irreversible), leukemia (secondary), leukopenia, lymphocytopenia, malignant neoplasm (secondary), neutropenia (onset: 3 weeks; recovery: 10 days after last dose), pancytopenia, thrombocytopenia

Hepatic: Hepatotoxicity, jaundice

Hypersensitivity: Angioedema, hypersensitivity reaction

Respiratory: Interstitial pneumonitis, pulmonary fibrosis

Miscellaneous: Fever

1%, postmarketing, and/or case reports: Agitation, ataxia, confusion, erythema multiforme, flaccid paralysis, seizure (focal/generalized), hallucination, muscle twitching, myoclonus, SIADH (syndrome of inappropriate antidiuretic hormone secretion), Stevens-Johnson syndrome, toxic epidermal necrolysis, tremor

Contraindications

Hypersensitivity to chlorambucil or any component of the formulation; hypersensitivity to other alkylating agents (may have cross-hypersensitivity); prior (demonstrated) resistance to chlorambucil

Canadian labeling: Additional contraindications (not in the US labeling): Use within 4 weeks of a full course of radiation or chemotherapy

Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult drug interactions database for more information.

Warnings/Precautions

Concerns related to adverse effects:

• Bone marrow suppression: [US Boxed Warning]: Chlorambucil may cause severe bone marrow suppression; neutropenia may be severe. Reduce initial dosage if patient has received myelosuppressive or radiation therapy within the previous 4 weeks, or has a depressed baseline leukocyte or platelet count. Irreversible bone marrow damage may occur with total doses approaching 6.5 mg/kg. Progressive lymphopenia may develop (recovery is generally rapid after discontinuation).

• Fertility effects: [US Boxed Warning]: Chlorambucil is probably mutagenic and teratogenic in humans. Chlorambucil produces human infertility.

• Secondary malignancy: [US Boxed Warning]: Chlorambucil is a human carcinogen; acute myelocytic leukemia and secondary malignancies may be associated with chronic therapy. Duration of treatment and higher cumulative doses are associated with a higher risk for development of leukemia.

• Seizures: Have been observed with use; patients with a history of nephrotic syndrome and high pulse doses are at higher risk of seizures. Use with caution in patients with a history of seizure disorder or head trauma.

• Skin reactions: Rare instances of severe skin reactions (eg, erythema multiforme, Stevens-Johnson syndrome, toxic epidermal necrolysis) have been reported; discontinue promptly if skin reaction occurs.

Disease-related concerns:

• Hepatic impairment: Chlorambucil is primarily metabolized in the liver. Dosage reductions should be considered in patients with hepatic impairment.

Other warnings/precautions:

• Vaccines: Avoid administration of live vaccines to immunocompromised patients.

Dosage Forms: US

Excipient information presented when available (limited, particularly for generics); consult specific product labeling.

Tablet, Oral:

Leukeran: 2 mg

Generic Equivalent Available: US

No

Pricing: US

Tablets (Leukeran Oral)

2 mg (per each): $666.07

Disclaimer: A representative AWP (Average Wholesale Price) price or price range is provided as reference price only. A range is provided when more than one manufacturer's AWP price is available and uses the low and high price reported by the manufacturers to determine the range. The pricing data should be used for benchmarking purposes only, and as such should not be used alone to set or adjudicate any prices for reimbursement or purchasing functions or considered to be an exact price for a single product and/or manufacturer. Medi-Span expressly disclaims all warranties of any kind or nature, whether express or implied, and assumes no liability with respect to accuracy of price or price range data published in its solutions. In no event shall Medi-Span be liable for special, indirect, incidental, or consequential damages arising from use of price or price range data. Pricing data is updated monthly.

Dosage Forms: Canada

Excipient information presented when available (limited, particularly for generics); consult specific product labeling.

Tablet, Oral:

Leukeran: 2 mg

Administration: Adult

Oral: May be administered as a single daily dose.

Administration: Pediatric

Oral: May be administered as a single daily dose; preferably on an empty stomach.

Hazardous Drugs Handling Considerations

Hazardous agent (NIOSH 2016 [group 1]).

Use appropriate precautions for receiving, handling, storage, preparation, dispensing, transporting, administration, and disposal. Follow NIOSH and USP 800 recommendations and institution-specific policies/procedures for appropriate containment strategy (NIOSH 2016; USP-NF 2020).

Use: Labeled Indications

Chronic lymphocytic leukemia: Management of chronic lymphocytic leukemia

Hodgkin lymphoma: Management of Hodgkin lymphoma

Non-Hodgkin lymphoma: Management of non-Hodgkin lymphomas

Use: Off-Label: Adult

Idiopathic membranous nephropathy; Necrobiotic xanthogranuloma; Waldenström macroglobulinemia, alternative agent

Medication Safety Issues
Sound-alike/look-alike issues:

Chlorambucil may be confused with Chloromycetin

Leukeran may be confused with Alkeran, leucovorin, Leukine, Myleran

High alert medication:

This medication is in a class the Institute for Safe Medication Practices (ISMP) includes among its list of drug classes which have a heightened risk of causing significant patient harm when used in error.

Metabolism/Transport Effects

None known.

Drug Interactions

Note: Interacting drugs may not be individually listed below if they are part of a group interaction (eg, individual drugs within “CYP3A4 Inducers [Strong]” are NOT listed). For a complete list of drug interactions by individual drug name and detailed management recommendations, use the Lexicomp drug interactions program by clicking on the “Launch drug interactions program” link above.

5-Aminosalicylic Acid Derivatives: May enhance the myelosuppressive effect of Myelosuppressive Agents. Risk C: Monitor therapy

Abrocitinib: May enhance the immunosuppressive effect of Immunosuppressants (Cytotoxic Chemotherapy). Risk X: Avoid combination

Antithymocyte Globulin (Equine): Immunosuppressants (Cytotoxic Chemotherapy) may enhance the adverse/toxic effect of Antithymocyte Globulin (Equine). Specifically, these effects may be unmasked if the dose of cytotoxic chemotherapy is reduced. Immunosuppressants (Cytotoxic Chemotherapy) may enhance the immunosuppressive effect of Antithymocyte Globulin (Equine). Specifically, infections may occur with greater severity and/or atypical presentations. Risk C: Monitor therapy

Baricitinib: Immunosuppressants (Cytotoxic Chemotherapy) may enhance the immunosuppressive effect of Baricitinib. Risk X: Avoid combination

BCG (Intravesical): Myelosuppressive Agents may diminish the therapeutic effect of BCG (Intravesical). Risk X: Avoid combination

BCG Products: Immunosuppressants (Cytotoxic Chemotherapy) may enhance the adverse/toxic effect of BCG Products. Specifically, the risk of vaccine-associated infection may be increased. Immunosuppressants (Cytotoxic Chemotherapy) may diminish the therapeutic effect of BCG Products. Risk X: Avoid combination

Brincidofovir: Immunosuppressants (Cytotoxic Chemotherapy) may diminish the therapeutic effect of Brincidofovir. Risk C: Monitor therapy

Brivudine: May enhance the adverse/toxic effect of Immunosuppressants (Cytotoxic Chemotherapy). Risk X: Avoid combination

Chikungunya Vaccine (Live): Immunosuppressants (Cytotoxic Chemotherapy) may enhance the adverse/toxic effect of Chikungunya Vaccine (Live). Specifically, the risk of vaccine-associated infection may be increased. Immunosuppressants (Cytotoxic Chemotherapy) may diminish the therapeutic effect of Chikungunya Vaccine (Live). Risk X: Avoid combination

Chloramphenicol (Ophthalmic): May enhance the adverse/toxic effect of Myelosuppressive Agents. Risk C: Monitor therapy

Chloramphenicol (Systemic): Myelosuppressive Agents may enhance the myelosuppressive effect of Chloramphenicol (Systemic). Risk X: Avoid combination

Cladribine: May enhance the myelosuppressive effect of Myelosuppressive Agents. Risk X: Avoid combination

Cladribine: Immunosuppressants (Cytotoxic Chemotherapy) may enhance the immunosuppressive effect of Cladribine. Risk X: Avoid combination

CloZAPine: Myelosuppressive Agents may enhance the adverse/toxic effect of CloZAPine. Specifically, the risk for neutropenia may be increased. Risk C: Monitor therapy

Coccidioides immitis Skin Test: Immunosuppressants (Cytotoxic Chemotherapy) may diminish the diagnostic effect of Coccidioides immitis Skin Test. Management: Consider discontinuing cytotoxic chemotherapy several weeks prior to coccidioides immitis skin antigen testing to increase the likelihood of accurate diagnostic results. Risk D: Consider therapy modification

COVID-19 Vaccine (Adenovirus Vector): Immunosuppressants (Cytotoxic Chemotherapy) may diminish the therapeutic effect of COVID-19 Vaccine (Adenovirus Vector). Management: Administer a 2nd dose using an mRNA COVID-19 vaccine (at least 4 weeks after the primary vaccine dose) and a bivalent booster dose (at least 2 months after the additional mRNA dose or any other boosters). Risk D: Consider therapy modification

COVID-19 Vaccine (Inactivated Virus): Immunosuppressants (Cytotoxic Chemotherapy) may diminish the therapeutic effect of COVID-19 Vaccine (Inactivated Virus). Risk C: Monitor therapy

COVID-19 Vaccine (mRNA): Immunosuppressants (Cytotoxic Chemotherapy) may diminish the therapeutic effect of COVID-19 Vaccine (mRNA). Management: Give a 3-dose primary series for all patients aged 6 months and older taking immunosuppressive medications or therapies. Booster doses are recommended for certain age groups. See CDC guidance for details. Risk D: Consider therapy modification

COVID-19 Vaccine (Subunit): Immunosuppressants (Cytotoxic Chemotherapy) may diminish the therapeutic effect of COVID-19 Vaccine (Subunit). Risk C: Monitor therapy

COVID-19 Vaccine (Virus-like Particles): Immunosuppressants (Cytotoxic Chemotherapy) may diminish the therapeutic effect of COVID-19 Vaccine (Virus-like Particles). Risk C: Monitor therapy

Deferiprone: Myelosuppressive Agents may enhance the neutropenic effect of Deferiprone. Management: Avoid the concomitant use of deferiprone and myelosuppressive agents whenever possible. If this combination cannot be avoided, monitor the absolute neutrophil count more closely. Risk D: Consider therapy modification

Dengue Tetravalent Vaccine (Live): Immunosuppressants (Cytotoxic Chemotherapy) may enhance the adverse/toxic effect of Dengue Tetravalent Vaccine (Live). Specifically, the risk of vaccine-associated infection may be increased. Immunosuppressants (Cytotoxic Chemotherapy) may diminish the therapeutic effect of Dengue Tetravalent Vaccine (Live). Risk X: Avoid combination

Denosumab: May enhance the immunosuppressive effect of Immunosuppressants (Cytotoxic Chemotherapy). Management: Consider the risk of serious infections versus the potential benefits of coadministration of denosumab and cytotoxic chemotherapy. If combined, monitor patients for signs/symptoms of serious infections. Risk D: Consider therapy modification

Deucravacitinib: May enhance the immunosuppressive effect of Immunosuppressants (Cytotoxic Chemotherapy). Risk X: Avoid combination

Dipyrone: May enhance the adverse/toxic effect of Myelosuppressive Agents. Specifically, the risk for agranulocytosis and pancytopenia may be increased Risk X: Avoid combination

Etrasimod: May enhance the immunosuppressive effect of Immunosuppressants (Cytotoxic Chemotherapy). Risk X: Avoid combination

Fexinidazole: Myelosuppressive Agents may enhance the myelosuppressive effect of Fexinidazole. Risk X: Avoid combination

Filgotinib: May enhance the immunosuppressive effect of Immunosuppressants (Cytotoxic Chemotherapy). Risk X: Avoid combination

Inebilizumab: Immunosuppressants (Cytotoxic Chemotherapy) may enhance the immunosuppressive effect of Inebilizumab. Risk C: Monitor therapy

Influenza Virus Vaccines: Immunosuppressants (Cytotoxic Chemotherapy) may diminish the therapeutic effect of Influenza Virus Vaccines. Management: Administer influenza vaccines at least 2 weeks prior to initiating chemotherapy if possible. If vaccination occurs less than 2 weeks prior to or during chemotherapy, revaccinate at least 3 months after therapy discontinued if immune competence restored. Risk D: Consider therapy modification

Leflunomide: Immunosuppressants (Cytotoxic Chemotherapy) may enhance the immunosuppressive effect of Leflunomide. Management: Increase the frequency of chronic monitoring of platelet, white blood cell count, and hemoglobin or hematocrit to monthly, instead of every 6 to 8 weeks, if leflunomide is coadministered with immunosuppressive agents, such as cytotoxic chemotherapy. Risk D: Consider therapy modification

Lenograstim: Antineoplastic Agents may diminish the therapeutic effect of Lenograstim. Management: Avoid the use of lenograstim 24 hours before until 24 hours after the completion of myelosuppressive cytotoxic chemotherapy. Risk D: Consider therapy modification

Lipegfilgrastim: Antineoplastic Agents may diminish the therapeutic effect of Lipegfilgrastim. Management: Avoid concomitant use of lipegfilgrastim and myelosuppressive cytotoxic chemotherapy. Lipegfilgrastim should be administered at least 24 hours after the completion of myelosuppressive cytotoxic chemotherapy. Risk D: Consider therapy modification

Mumps- Rubella- or Varicella-Containing Live Vaccines: Immunosuppressants (Cytotoxic Chemotherapy) may enhance the adverse/toxic effect of Mumps- Rubella- or Varicella-Containing Live Vaccines. Specifically, the risk of vaccine-associated infection may be increased. Immunosuppressants (Cytotoxic Chemotherapy) may diminish the therapeutic effect of Mumps- Rubella- or Varicella-Containing Live Vaccines. Risk X: Avoid combination

Nadofaragene Firadenovec: Immunosuppressants (Cytotoxic Chemotherapy) may enhance the adverse/toxic effect of Nadofaragene Firadenovec. Specifically, the risk of disseminated adenovirus infection may be increased. Risk X: Avoid combination

Natalizumab: Immunosuppressants (Cytotoxic Chemotherapy) may enhance the immunosuppressive effect of Natalizumab. Risk X: Avoid combination

Ocrelizumab: Immunosuppressants (Cytotoxic Chemotherapy) may enhance the immunosuppressive effect of Ocrelizumab. Risk C: Monitor therapy

Ofatumumab: Immunosuppressants (Cytotoxic Chemotherapy) may enhance the immunosuppressive effect of Ofatumumab. Risk C: Monitor therapy

Olaparib: Myelosuppressive Agents may enhance the myelosuppressive effect of Olaparib. Risk C: Monitor therapy

Palifermin: May enhance the adverse/toxic effect of Antineoplastic Agents. Specifically, the duration and severity of oral mucositis may be increased. Management: Do not administer palifermin within 24 hours before, during infusion of, or within 24 hours after administration of myelotoxic chemotherapy. Risk D: Consider therapy modification

Pidotimod: Immunosuppressants (Cytotoxic Chemotherapy) may diminish the therapeutic effect of Pidotimod. Risk C: Monitor therapy

Pimecrolimus: May enhance the immunosuppressive effect of Immunosuppressants (Cytotoxic Chemotherapy). Risk X: Avoid combination

Pneumococcal Vaccines: Immunosuppressants (Cytotoxic Chemotherapy) may diminish the therapeutic effect of Pneumococcal Vaccines. Risk C: Monitor therapy

Poliovirus Vaccine (Live/Trivalent/Oral): Immunosuppressants (Cytotoxic Chemotherapy) may enhance the adverse/toxic effect of Poliovirus Vaccine (Live/Trivalent/Oral). Specifically, the risk of vaccine-associated infection may be increased. Immunosuppressants (Cytotoxic Chemotherapy) may diminish the therapeutic effect of Poliovirus Vaccine (Live/Trivalent/Oral). Risk X: Avoid combination

Polymethylmethacrylate: Immunosuppressants (Cytotoxic Chemotherapy) may enhance the potential for allergic or hypersensitivity reactions to Polymethylmethacrylate. Management: Use caution when considering use of bovine collagen-containing implants such as the polymethylmethacrylate-based Bellafill brand implant in patients who are receiving immunosuppressants. Consider use of additional skin tests prior to administration. Risk D: Consider therapy modification

Promazine: May enhance the myelosuppressive effect of Myelosuppressive Agents. Risk C: Monitor therapy

Rabies Vaccine: Immunosuppressants (Cytotoxic Chemotherapy) may diminish the therapeutic effect of Rabies Vaccine. Management: Complete rabies vaccination at least 2 weeks before initiation of immunosuppressant therapy if possible. If combined, check for rabies antibody titers, and if vaccination is for post exposure prophylaxis, administer a 5th dose of the vaccine. Risk D: Consider therapy modification

Ritlecitinib: Immunosuppressants (Cytotoxic Chemotherapy) may enhance the immunosuppressive effect of Ritlecitinib. Risk X: Avoid combination

Ropeginterferon Alfa-2b: Myelosuppressive Agents may enhance the myelosuppressive effect of Ropeginterferon Alfa-2b. Management: Avoid coadministration of ropeginterferon alfa-2b and other myelosuppressive agents. If this combination cannot be avoided, monitor patients for excessive myelosuppressive effects. Risk D: Consider therapy modification

Ruxolitinib (Topical): Immunosuppressants (Cytotoxic Chemotherapy) may enhance the immunosuppressive effect of Ruxolitinib (Topical). Risk X: Avoid combination

Sipuleucel-T: Immunosuppressants (Cytotoxic Chemotherapy) may diminish the therapeutic effect of Sipuleucel-T. Management: Consider reducing the dose or discontinuing the use of immunosuppressants, such as cytotoxic chemotherapy, prior to initiating sipuleucel-T therapy. Risk D: Consider therapy modification

Sphingosine 1-Phosphate (S1P) Receptor Modulator: May enhance the immunosuppressive effect of Immunosuppressants (Cytotoxic Chemotherapy). Risk C: Monitor therapy

Tacrolimus (Topical): Immunosuppressants (Cytotoxic Chemotherapy) may enhance the immunosuppressive effect of Tacrolimus (Topical). Risk X: Avoid combination

Talimogene Laherparepvec: Immunosuppressants (Cytotoxic Chemotherapy) may enhance the adverse/toxic effect of Talimogene Laherparepvec. Specifically, the risk of infection from the live, attenuated herpes simplex virus contained in talimogene laherparepvec may be increased. Risk X: Avoid combination

Tertomotide: Immunosuppressants (Cytotoxic Chemotherapy) may diminish the therapeutic effect of Tertomotide. Risk X: Avoid combination

Tofacitinib: Immunosuppressants (Cytotoxic Chemotherapy) may enhance the immunosuppressive effect of Tofacitinib. Risk X: Avoid combination

Typhoid Vaccine: Immunosuppressants (Cytotoxic Chemotherapy) may enhance the adverse/toxic effect of Typhoid Vaccine. Specifically, the risk of vaccine-associated infection may be increased. Immunosuppressants (Cytotoxic Chemotherapy) may diminish the therapeutic effect of Typhoid Vaccine. Risk X: Avoid combination

Ublituximab: Immunosuppressants (Cytotoxic Chemotherapy) may enhance the immunosuppressive effect of Ublituximab. Risk C: Monitor therapy

Upadacitinib: Immunosuppressants (Cytotoxic Chemotherapy) may enhance the immunosuppressive effect of Upadacitinib. Risk X: Avoid combination

Vaccines (Inactivated/Non-Replicating): Immunosuppressants (Cytotoxic Chemotherapy) may diminish the therapeutic effect of Vaccines (Inactivated/Non-Replicating). Management: Give inactivated vaccines at least 2 weeks prior to initiation of chemotherapy when possible. Patients vaccinated less than 14 days before initiating or during chemotherapy should be revaccinated at least 3 months after therapy is complete. Risk D: Consider therapy modification

Vaccines (Live): Immunosuppressants (Cytotoxic Chemotherapy) may enhance the adverse/toxic effect of Vaccines (Live). Specifically, the risk of vaccine-associated infection may be increased. Vaccines (Live) may diminish the therapeutic effect of Immunosuppressants (Cytotoxic Chemotherapy). Risk X: Avoid combination

Yellow Fever Vaccine: Immunosuppressants (Cytotoxic Chemotherapy) may enhance the adverse/toxic effect of Yellow Fever Vaccine. Specifically, the risk of vaccine-associated infection may be increased. Immunosuppressants (Cytotoxic Chemotherapy) may diminish the therapeutic effect of Yellow Fever Vaccine. Risk X: Avoid combination

Food Interactions

Absorption is decreased when administered with food. Management: Administer preferably on an empty stomach.

Reproductive Considerations

[US Boxed Warning]: Chlorambucil produces human infertility. Chromosomal damage has been documented. Reversible and irreversible sterility (when administered to prepubertal and pubertal males), azoospermia (in adult males), and amenorrhea (in females) have been observed. Fibrosis, vasculitis, and depletion of primordial follicles have been noted on autopsy of the ovaries.

Women of childbearing potential should avoid becoming pregnant while receiving treatment.

Pregnancy Considerations

Following exposure during the first trimester, case reports have noted adverse renal effects (unilateral agenesis) in the newborn.

[US Boxed Warning]: Chlorambucil is probably mutagenic and teratogenic in humans.

Breastfeeding Considerations

It is not known if chlorambucil is present in breast milk.

Due to the potential for serious adverse reactions in the breastfed infant, the decision to discontinue chlorambucil or to discontinue breastfeeding should consider the benefits of treatment to the mother.

Monitoring Parameters

Monitor LFTs, CBC with differential (weekly, with WBC monitored twice weekly during the first 3 to 6 weeks of treatment). Monitor adherence.

The American Society of Clinical Oncology hepatitis B virus (HBV) screening and management provisional clinical opinion (ASCO [Hwang 2020]) recommends HBV screening with hepatitis B surface antigen, hepatitis B core antibody, total Ig or IgG, and antibody to hepatitis B surface antigen prior to beginning (or at the beginning of) systemic anticancer therapy; do not delay treatment for screening/results. Detection of chronic or past HBV infection requires a risk assessment to determine antiviral prophylaxis requirements, monitoring, and follow-up.

Mechanism of Action

Chlorambucil is an alkylating agent that interferes with DNA replication and RNA transcription by alkylation and cross-linking the strands of DNA, inducing cellular apoptosis.

Pharmacokinetics (Adult Data Unless Noted)

Absorption: Rapid and complete (>70%) from GI tract; reduced with food

Distribution: Vd: ~0.31 L/kg

Protein binding: ~99%; primarily to albumin

Metabolism: Hepatic (extensively); primarily to active metabolite, phenylacetic acid mustard; chlorambucil and phenylacetic acid mustard undergo oxidative degradation

Half-life elimination: Chlorambucil: ~1.5 hours; Phenylacetic acid mustard: 1.8 ± 0.4 hours

Time to peak, plasma: Chlorambucil: Within 1 hour; Phenylacetic acid mustard: 1.9 ± 0.7 hours

Excretion: Urine (~20% to 60% within 24 hours, primarily as inactive metabolites, <1% as unchanged drug or phenylacetic acid mustard)

Brand Names: International
International Brand Names by Country
For country code abbreviations (show table)

  • (AE) United Arab Emirates: Leukeran;
  • (AR) Argentina: Leukeran;
  • (AT) Austria: Leukeran;
  • (AU) Australia: Leukeran;
  • (BD) Bangladesh: Leukeran;
  • (BE) Belgium: Leukeran;
  • (BG) Bulgaria: Leukeran;
  • (BR) Brazil: Leukeran;
  • (CH) Switzerland: Leukeran;
  • (CL) Chile: Clorambucilo | Leukeran;
  • (CN) China: Leukeran;
  • (CO) Colombia: Leukeran;
  • (CZ) Czech Republic: Chlorobutin | Leukeran;
  • (DE) Germany: Leukeran;
  • (DO) Dominican Republic: Leukeran;
  • (EC) Ecuador: Leukeran;
  • (EE) Estonia: Leukeran;
  • (EG) Egypt: Leukeran;
  • (ES) Spain: Clorambucilo aspen | Leukeran;
  • (FI) Finland: Chlorambusil | Leukeran;
  • (FR) France: Chloraminophene;
  • (GB) United Kingdom: Leukeran;
  • (GR) Greece: Leukeran;
  • (HK) Hong Kong: Leukeran;
  • (HU) Hungary: Chlorbutin | Leukeran;
  • (IE) Ireland: Leukeran;
  • (IL) Israel: Leukeran;
  • (IN) India: Celkeran | Chloramax | Clokeran | Leukeran;
  • (IT) Italy: Leukeran;
  • (JO) Jordan: Leukeran;
  • (KE) Kenya: Leukeran;
  • (KR) Korea, Republic of: Leukeran;
  • (KW) Kuwait: Leukeran;
  • (LB) Lebanon: Leukeran;
  • (LT) Lithuania: Chlorobutin | Leukeran;
  • (LU) Luxembourg: Leukeran;
  • (LV) Latvia: Chlorobutin | Leukeran;
  • (MX) Mexico: Leukeran;
  • (MY) Malaysia: Leukeran;
  • (NL) Netherlands: Leukeran;
  • (NO) Norway: Leukeran;
  • (NZ) New Zealand: Leukeran;
  • (PH) Philippines: Leukeran;
  • (PL) Poland: Chlorobutin | Leukeran;
  • (PR) Puerto Rico: Leukeran;
  • (PT) Portugal: Leukeran;
  • (QA) Qatar: Leukeran;
  • (RO) Romania: Leukeran;
  • (RU) Russian Federation: Chlorbutin | Chlorobutin | Leukeran | Loramyl;
  • (SA) Saudi Arabia: Leukeran;
  • (SE) Sweden: Leukeran;
  • (SG) Singapore: Leukeran;
  • (SI) Slovenia: Leukeran;
  • (SK) Slovakia: Leukeran;
  • (TH) Thailand: Leukeran;
  • (TN) Tunisia: Leukeran;
  • (TR) Turkey: Leukeran;
  • (TW) Taiwan: Leukeran;
  • (UA) Ukraine: Leukeran;
  • (UY) Uruguay: Leukeran | Linfoxan;
  • (ZA) South Africa: Leukeran
  1. <800> Hazardous Drugs—Handling in Healthcare Settings. United States Pharmacopeia and National Formulary (USP 43-NF 38). Rockville, MD: United States Pharmacopeia Convention; 2020:74-92.
  2. Aronoff GR, Bennett WM, Berns JS, et al. Drug Prescribing in Renal Failure: Dosing Guidelines for Adults and Children. 5th ed. American College of Physicians; 2007:98.
  3. Atra A, Higgs, E, Capra M, et al. ChlVPP chemotherapy in children with stage IV Hodgkin’s disease: results of the UKCCSG HD 8201 and HD 9201 studies. Br J Hematol. 2002;119:647-651.
  4. Baluarte HJ, Hiner L, Gruskin AB. Chlorambucil Dosage in Frequently Relapsing Nephrotic Syndrome: A Controlled Clinical Trial. J Pediatr. 1978;92(2):295-298. [PubMed 621612]
  5. Berk PD, Goldberg JD, Silverstein MN, et al. Increased incidence of acute leukemia in polycythemia vera associated with chlorambucil therapy. N Engl J Med. 1981;304(8):441-447. doi:10.1056/NEJM198102193040801 [PubMed 7005681]
  6. Capra M, Hewitt M, Radford M, et al. Long-term outcome in children with Hodgkin's lymphoma: the United Kingdom Children's Cancer Study Group HD82 trial. Eur J Cancer. 2007;43(7):1171-1179. [PubMed 17379506]
  7. Eichhorst BF, Busch R, Stilgenbauer S, et al; German CLL Study Group (GCLLSG). First-line therapy with fludarabine compared with chlorambucil does not result in a major benefit for elderly patients with advanced chronic lymphocytic leukemia. Blood. 2009;114(16):3382-3391. doi:10.1182/blood-2009-02-206185 [PubMed 19605849]
  8. Finan MC, Winkelmann RK. Necrobiotic xanthogranuloma with paraproteinemia. A review of 22 cases. Medicine (Baltimore). 1986;65(6):376-388. doi:10.1097/00005792-198611000-00003 [PubMed 3097454]
  9. Gertz MA. Waldenström macroglobulinemia: 2019 update on diagnosis, risk stratification, and management. Am J Hematol. 2019;94(2):266-276. doi:10.1002/ajh.25292 [PubMed 30328142]
  10. Gipson DS, Massengill SF, Yao L, et al. Management of childhood onset nephrotic syndrome. Pediatrics. 2009;124(2):747-757. [PubMed 19651590]
  11. Goede V, Fischer K, Busch R, et al. Obinutuzumab plus chlorambucil in patients with CLL and coexisting conditions. N Engl J Med. 2014;370(12):1101-1110. doi:10.1056/NEJMoa1313984 [PubMed 24401022]
  12. Griggs JJ, Bohlke K, Balaban EP, et al. Appropriate systemic therapy dosing for obese adult patients with cancer: ASCO guideline update. J Clin Oncol. 2021;39(18):2037-2048. doi:10.1200/JCO.21.00471 [PubMed 33939491]
  13. Hall GW, Katzilakis N, Pinkerton CR, et al. Outcome of children with nodular lymphocyte predominant Hodgkin lymphoma – a Children’s Cancer and Leukaemia Group report. Br J Hematol, 2007;138;761-768. [PubMed 17760808]
  14. Hilal T, DiCaudo DJ, Connolly SM, Reeder CB. Necrobiotic xanthogranuloma: a 30-year single-center experience. Ann Hematol. 2018;97(8):1471-1479. doi: 10.1007/s00277-018-3301-1. [PubMed 29568990]
  15. Hillmen P, Gribben JG, Follows GA, et al. Rituximab plus chlorambucil as first-line treatment for chronic lymphocytic leukemia: Final analysis of an open-label phase II study. J Clin Oncol. 2014;32(12):1236-1241. doi:10.1200/JCO.2013.49.6547 [PubMed 24638012]
  16. Hillmen P, Robak T, Janssens A, et al; COMPLEMENT 1 Study Investigators. Chlorambucil plus ofatumumab versus chlorambucil alone in previously untreated patients with chronic lymphocytic leukaemia (COMPLEMENT 1): a randomised, multicentre, open-label phase 3 trial. Lancet. 2015;385(9980):1873-1883. doi:10.1016/S0140-6736(15)60027-7 [PubMed 25882396]
  17. Hodson EM, Willis NS, Craig JC. Non-Corticosteroid Treatment for Nephrotic Syndrome in Children (Review).Cochrane Database Syst Rev. 2010;(4):CD002290. [PubMed 18254005]
  18. Howman A, Chapman TL, Langdon MM, et al. Immunosuppression for progressive membranous nephropathy: a UK randomised controlled trial. Lancet. 2013;381(9868):744-751. doi:10.1016/S0140-6736(12)61566-9 [PubMed 23312808]
  19. Hwang JP, Feld JJ, Hammond SP, et al. Hepatitis B virus screening and management for patients with cancer prior to therapy: ASCO provisional clinical opinion update. J Clin Oncol. 2020;38(31):3698-3715. doi:10.1200/JCO.20.01757 [PubMed 32716741]
  20. Kidney Disease: Improving Global Outcomes (KDIGO) Glomerulonephritis Work Group. KDIGO clinical practice guideline for glomerulonephritis. Kidney Inter. 2012;2:139-274.
  21. Kintzel PE, Dorr RT. Anticancer drug renal toxicity and elimination: dosing guidelines for altered renal function. Cancer Treat Rev. 1995;21(1):33-64. [PubMed 7859226]
  22. Kyle RA, Greipp PR, Gertz MA, et al. Waldenström's macroglobulinemia: a prospective study comparing daily with intermittent oral chlorambucil. Br J Haematol. 2000;108(4):737-742. [PubMed 10792277]
  23. Leblond V, Johnson S, Chevret S, et al. Results of a randomized trial of chlorambucil versus fludarabine for patients with untreated Waldenström macroglobulinemia, marginal zone lymphoma, or lymphoplasmacytic lymphoma. J Clin Oncol. 2013;31(3):301-307. doi:10.1200/JCO.2012.44.7920 [PubMed 23233721]
  24. Lepretre S, Dartigeas C, Feugier P, Marty M, Salles G. Systematic review of the recent evidence for the efficacy and safety of chlorambucil in the treatment of B-cell malignancies. Leuk Lymphoma. 2016;57(4):852-865. doi:10.3109/10428194.2015.1085528 [PubMed 26308278]
  25. Leukeran (chlorambucil) (prescribing information). Wixom, MI: Waylis Therapeutics LLC; February 2023.
  26. Leukeran (chlorambucil) [product monograph]. Oakville, Ontario, Canada: Aspen Pharmacare Canada Inc; July 2019.
  27. Martinelli G, Laszlo D, Bertolini F, et al. Chlorambucil in combination with induction and maintenance rituximab is feasible and active in indolent non-Hodgkin's lymphoma. Br J Haematol. 2003;123(2):271-277. doi:10.1046/j.1365-2141.2003.04586.x [PubMed 14531908]
  28. Martinelli G, Montoro J, Vanazzi A, et al. Chlorambucil-rituximab as first-line therapy in patients affected by follicular non-Hodgkin's lymphoma: a retrospective single-centre study. Hematol Oncol. 2015;33(4):129-135. doi:10.1002/hon.2154 [PubMed 25047267]
  29. McMullin MF, Bareford D, Campbell P, et al; General Haematology Task Force of the British Committee for Standards in Haematology. Guidelines for the diagnosis, investigation and management of polycythaemia/erythrocytosis. Br J Haematol. 2005;130(2):174-195. doi:10.1111/j.1365-2141.2005.05535.x [PubMed 16029446]
  30. McMullin MFF, Mead AJ, Ali S, et al; British Society for Haematology. A guideline for the management of specific situations in polycythaemia vera and secondary erythrocytosis: A British Society for Haematology guideline. Br J Haematol. 2019;184(2):161-175. doi:10.1111/bjh.15647 [PubMed 30426472]
  31. Mehregan DA, Winkelmann RK. Necrobiotic xanthogranuloma [published correction appears in Arch Dermatol. 1992;128(5):632]. Arch Dermatol. 1992;128(1):94-100. [PubMed 1739294]
  32. Miguel D, Lukacs J, Illing T, Elsner P. Treatment of necrobiotic xanthogranuloma - a systematic review. J Eur Acad Dermatol Venereol. 2017;31(2):221-235. doi:10.1111/jdv.13786 [PubMed 27436448]
  33. Nahata MC, Pai VB, Hipple TF. Pediatric Drug Formulations. 5th ed. Cincinnati, OH: Harvey Whitney Books Co; 2004.
  34. Paw Cho Sing E, Robinson PD, Flank J, et al. Classification of the acute emetogenicity of chemotherapy in pediatric patients: A clinical practice guideline. Pediatr Blood Cancer. 2019;66(5):e27646. [PubMed 30729654]
  35. Rai KR, Peterson BL, Appelbaum FR, et al. Fludarabine compared with chlorambucil as primary therapy for chronic lymphocytic leukemia. N Engl J Med. 2000;343(24):1750-1757. doi:10.1056/NEJM200012143432402 [PubMed 11114313]
  36. Raphael B, Andersen JW, Silber R, et al. Comparison of chlorambucil and prednisone versus cyclophosphamide, vincristine, and prednisone as initial treatment for chronic lymphocytic leukemia: long-term follow-up of an Eastern Cooperative Oncology Group randomized clinical trial. J Clin Oncol. 1991;9(5):770-776. doi:10.1200/JCO.1991.9.5.770 [PubMed 2016618]
  37. Robinson RF, Nahata MC, Mahan JD. Management of Nephrotic Syndrome in Children. Pharmacotherapy. 2003;23(8):1021-1036. [PubMed 12921248]
  38. Ryan E, Warren LJ, Szabo F. Necrobiotic xanthogranuloma: response to chlorambucil. Australas J Dermatol. 2012;53(2):e23-e25. doi:10.1111/j.1440-0960.2010.00710.x [PubMed 22571578]
  39. Selby P, Patel P, Milan S, et al. ChlVPP combination chemotherapy for Hodgkin's disease: long-term results. Br J Cancer. 1990;62(2):279-285. doi:10.1038/bjc.1990.278 [PubMed 2386744 ]
  40. Singh BN, Malhotra BK. Effects of Food on the Clinical Pharmacokinetics of Anticancer Agents: Underlying Mechanisms and Implications for Oral Chemotherapy. Clin Pharmacokinet. 2004;43(15):1127-1156. [PubMed 15568891]
  41. Stoneham S, Ashley S, Pinkerton R, Hewitt M, Wallace WHP, Shankar AG. Hodgkin’s lymphoma in children aged 5 years or less – the United Kingdom experience. Eur J Cancer. 2007;43:1415-1421. [PubMed 17509875]
  42. Szalat R, Arnulf B, Karlin L, et al. Pathogenesis and treatment of xanthomatosis associated with monoclonal gammopathy. Blood. 2011;118(14):3777-3784. doi:10.1182/blood-2011-05-356907 [PubMed 21757618]
  43. The International ChlVPP Treatment Group. ChlVPP Therapy for Hodgkin’s Disease: Experience of 960 Patients. Ann Oncol. 1995;6(2):167-172. [PubMed 7786824]
  44. US Department of Health and Human Services; Centers for Disease Control and Prevention; National Institute for Occupational Safety and Health. NIOSH list of antineoplastic and other hazardous drugs in healthcare settings 2016. https://www.cdc.gov/niosh/docs/2016-161/default.html. Updated September 2016. Accessed October 5, 2016.
  45. Vannucchi AM, Barbui T, Cervantes F, et al; ESMO Guidelines Committee. Philadelphia chromosome–negative chronic myeloproliferative neoplasms: ESMO clinical practice guidelines for diagnosis, treatment and follow-up. Ann Oncol. 2015;26(suppl 5):v85‐v99. doi:10.1093/annonc/mdv203 [PubMed 26242182]
  46. Vose JM, Bierman PJ, Anderson JR, et al. CHLVPP chemotherapy with involved-field irradiation for Hodgkin’s disease: favorable results with acceptable toxicity. J Clin Oncol. 1991;9(8):1421-1425. doi:10.1200/JCO.1991.9.8.1421 [PubMed 2072145]
  47. Wagner AM, Brunet S, Puig J, et al. Chlorambucil-Induced Inappropriate Antidiuresis in Man With Chronic Lymphocytic Leukemia. Ann Hemat. 1999;78(1):37-38.
  48. Wells J, Gillespie R, Zardawi I. Case of recalcitrant necrobiotic xanthogranuloma. Australas J Dermatol. 2004;45(4):213-215. doi:10.1111/j.1440-0960.2004.00099.x [PubMed 15527430]
  49. Williams SA, Makker SP, Grupe WE. Seizures: A Significant Side Effect of Chlorambucil Therapy in Children. J Pediatr. 1978;93(3):516-518. [PubMed 690782]
  50. Wood AJ, Wagner MV, Abbott JJ, Gibson LE. Necrobiotic xanthogranuloma: a review of 17 cases with emphasis on clinical and pathologic correlation. Arch Dermatol. 2009;145(3):279-284. doi:10.1001/archdermatol.2008.583 [PubMed 19289757]
  51. Zucca E, Conconi A, Martinelli G, et al. final results of the ielsg-19 randomized trial of mucosa-associated lymphoid tissue lymphoma: improved event-free and progression-free survival with rituximab plus chlorambucil versus either chlorambucil or rituximab monotherapy. J Clin Oncol. 2017;35(17):1905-1912. doi:10.1200/JCO.2016.70.6994 [PubMed 28355112]
Topic 9240 Version 286.0

آیا می خواهید مدیلیب را به صفحه اصلی خود اضافه کنید؟