Alemtuzumab

Class: Antineoplastic Agents
VA Class: AN900
Brands: Campath

Warning(s)

  • Risk of serious and, rarely, fatal pancytopenia/marrow hypoplasia, autoimmune idiopathic thrombocytopenia, and autoimmune hemolytic anemia.1 Do not administer single doses >30 mg or cumulative weekly doses >90 mg, since these dosages have been associated with an increased incidence of pancytopenia.1 (See Dosage under Dosage and Administration and see Hematologic Effects under Cautions.)

  • Possible serious or fatal infusion reactions.1 Monitor patients carefully during infusions; discontinue therapy if indicated.1 Gradual titration to the recommended maintenance dosage is required during initiation of therapy and after interruption of therapy for ≥7 days.1 (See Dosage under Dosage and Administration and see Infusions Reactions under Cautions.)

  • Risk of serious and sometimes fatal bacterial, viral, fungal, and protozoan infections.1 Prophylaxis against Pneumocystis jiroveci (formerly P. carinii) pneumonia and herpesvirus infections may decrease, but not eliminate, the occurrence of these infections.1 (See General under Dosage and Administration and see Infectious Complications under Cautions.)

Introduction

Antineoplastic agent; recombinant DNA-derived humanized anti-CD52 monoclonal antibody.1

Uses for Alemtuzumab

Chronic Lymphocytic Leukemia (CLL)

First-line therapy of B-cell chronic lymphocytic leukemia (B-CLL).1 6 31 Comparative efficacy and safety of alemtuzumab versus fludarabine as initial therapy for B-CLL notestablished.3

Slideshow: Drug Treatment for Rheumatoid Arthritis - What Are Your Options?

Treatment of B-cell CLL (B-CLL) in patients who have been treated with alkylating agents and who have not responded adequately to fludarabine therapy (designated an orphan drug by FDA for this use).1 6 7 8

Under investigation for use in combination with fludarabine for the second-line treatment of relapsed or refractory B-CLL.30

Alemtuzumab Dosage and Administration

General

Premedication and Patient Monitoring

  • To minimize risk of IV infusion-related reactions, administer diphenhydramine hydrochloride 50 mg and acetaminophen 500–1000 mg 30 minutes prior to first alemtuzumab infusion and when dosage is escalated.1 (See Infusion-related Effects under Cautions.)

  • Monitor patients carefully during or shortly after infusion for manifestations of infusion reactions (e.g., rigors, fever, bronchospasm, chills, nausea, vomiting, rash, urticaria, dyspnea, hypotension).1

  • To minimize risk of injection site reactions, administer an antihistamine and acetaminophen prior to sub-Q injections (e.g., 30 minutes before administration);34 35 36 in one study, premedication was gradually withdrawn following resolution of any injection-related reactions.34

Anti-infective Prophylaxis

  • To minimize risk of serious opportunistic infections, give prophylactic anti-infectives upon initiation of alemtuzumab and continue for 2 months after completion of therapy or until CD4+ T-cell count ≥200/mm3 (whichever occurs later).1 (See Infectious Complications under Cautions.)

  • Administer co-trimoxazole (sulfamethoxazole 800 mg and trimethoprim 160 mg per dose) twice daily 3 times weekly (or equivalent) for prophylaxis of Pneumocystis jiroveci (formerly P. carinii) pneumonia.1

  • Administer famciclovir 250 mg twice daily (or equivalent) for prophylaxis of herpesvirus infection.1

Administration

Administer by IV infusion.1 May be administered by sub-Q injection.34 35 36

IV Administration

For solution compatibility information, see Compatibility under Stability.

Administer by IV infusion only.1 Do not administer by rapid IV injection (e.g., IV push or bolus).1

Do not mix with any other drug or administer any other drug simultaneously in the same IV line.1

Vials are for single use only.1

Dilution

Use strict aseptic technique since drug product contains no preservative.1

Do not shake vial prior to use.1 5

Withdraw appropriate dose of alemtuzumab concentrate into a syringe calibrated in increments of 0.01 mL when preparing a 3-mg dose or a 10-mg dose; for a 30-mg dose, use a syringe calibrated in increments of 0.1 mL.1 To prepare a 3-mg dose, withdraw 0.1 mL of alemtuzumab concentrate into a 1-mL syringe; to prepare a 10-mg dose, withdraw 0.33 mL into a 1-mL syringe; and to prepare a 30-mg dose, withdraw 1 mL into either a 1- or 3-mL syringe.1 Discard vial, including any unused portion, after withdrawal of dose.1

Add appropriate dose of alemtuzumab concentrate to 100 mL of 0.9% sodium chloride or 5% dextrose injection; gently invert bag to mix solution.1

Rate of Administration

Administer dose over 2 hours.1

Dosage

Adults

CLL

Gradual titration to the recommended maintenance dosage is required during initiation of therapy and after interruption of therapy for ≥7 days.1 In most patients, escalation to maintenance dosage can be accomplished in 3–7 days.1

IV

Initially, 3 mg daily.1 4 When infusion-related toxicities are ≤grade 2, increase dosage to 10 mg daily.1 4 Continue at this dosage until infusion-related toxicities are ≤grade 2, and then increase to a maintenance dosage of 30 mg 3 times weekly on alternate days (i.e., Monday, Wednesday, Friday).1 4 Total duration of therapy, including initial dosage and dosage escalation, is 12 weeks.1

Sub-Q

In some clinical trials, dose was escalated from an initial dosage of 3 mg daily to a maintenance dosage of 30 mg 3 times weekly.34 35 36 If local skin erythema or edema occurred, dosage escalation phase was prolonged to 1 or 2 weeks.34 36 (See Injection Site Reactions under Cautions.)

Some experts recommend that sub-Q therapy be given for at least 12 weeks.36 In a clinical trial in previously untreated patients, the drug was administered up to 18 weeks;34 in another clinical trial in previously treated patients, total duration of therapy was up to 12 weeks.35

Dosage Modification for Toxicity and Contraindications to Continued Therapy

Withhold therapy during serious adverse reactions until resolution of toxicity.1 Discontinuance of therapy may be necessary.1

Hematologic Toxicities

Adjust dosage and/or temporarily discontinue therapy if severe cytopenias (except lymphopenia) occur; permanently discontinue drug in patients with evidence of autoimmune hematologic toxicity (i.e., autoimmune anemia or thrombocytopenia).1

No dosage modifications recommended for lymphopenia.1

Dosage Adjustments for Hematologic Toxicities

Hematologic Measurements

Comments

For first occurrence of ANC <250/mm3 and/or platelets ≤25,000/mm3

Temporarily discontinue therapy.1 When ANC ≥500/mm3 and platelets ≥50,000/mm3, resume therapy at maintenance dosage (i.e., 30 mg 3 times weekly)1

If ≥7 days have elapsed since discontinuance of alemtuzumab, reinitiate therapy at 3 mg daily and escalate to 10 mg daily and then to 30 mg 3 times weekly as tolerated1

For second occurrence of ANC <250/mm3 and/or platelets ≤25,000/mm3

Temporarily discontinue therapy.1 When ANC ≥500/mm3 and platelets ≥50,000/mm3,1 resume therapy at 10 mg 3 times weekly;5 higher dosages not recommended1 5

If ≥7 days have elapsed since discontinuance of alemtuzumab, reinitiate therapy at 3 mg daily and escalate to 10 mg daily and then to 30 mg 3 times weekly as tolerated.1

For third occurrence of ANC <250/mm3 and/or platelets ≤25,000/mm3

Discontinue alemtuzumab permanently1

For first occurrence of a decrease of ANC and/or platelets by ≥50% from baseline value in patients initiating therapy with a baseline ANC ≤250/mm3 and/or baseline platelets ≤25,000/mm3

Temporarily discontinue therapy.1 When ANC and/or platelets return to baseline values, resume therapy at maintenance dosage (i.e., 30 mg 3 times weekly)1 5

If ≥7 days have elapsed since discontinuance of alemtuzumab, reinitiate therapy at 3 mg daily and escalate to 10 mg daily and then to 30 mg 3 times weekly as tolerated1

For second occurrence of a decrease of ANC and/or platelets by ≥50% from baseline value in patients initiating therapy with ANC of ≤250/mm3 and/or platelets ≤25,000/mm3

Temporarily discontinue therapy.1 When ANC and/or platelets return to baseline values, resume therapy at 10 mg 3 times weekly1

If ≥7 days have elapsed since discontinuance of alemtuzumab, reinitiate therapy at 3 mg daily and escalate to 10 mg 3 times weekly as tolerated1

For third occurrence of a decrease of ANC and/or platelets by ≥50% from baseline value in patients initiating therapy with ANC <250/mm3 and/or platelets ≤25,000/mm3

Discontinue alemtuzumab permanently1

Infusion Reactions

Withhold therapy in patients experiencing grade 3 or 4 infusion reactions.1

Infectious Complications

If serious infection occurs, temporarily discontinue therapy; may reinitiate therapy following resolution of infection.1

Withhold therapy during antiviral therapy for CMV infection or confirmed CMV viremia (defined as positive for CMV according to PCR in ≥2 consecutive samples obtained ≥1 week apart) and initiate anti-infective therapy (ganciclovir or equivalent).1

Prescribing Limits

Adults

CLL
IV

Maximum 30 mg (as single dose) or 90 mg (as cumulative weekly dose); maximum 12 weeks total duration of therapy, including initial dosage and dosage escalation.1 (See Boxed Warning and see Hematologic Effects under Cautions.)

Special Populations

Geriatric Patients

No dosage adjustment required.1

Cautions for Alemtuzumab

Contraindications

  • None.1

Warnings/Precautions

Warnings

Use under supervision of a qualified clinician experienced in therapy with antineoplastic agents.1

Hematologic Effects

Risk of severe (sometimes fatal) autoimmune anemia, autoimmune thrombocytopenia, and prolonged myelosuppression.1 5 Hemolytic anemia, pure red cell aplasia, bone marrow aplasia, and hypoplasia have occurred in patients receiving recommended dosage.1 Increased incidence of pancytopenia with higher than recommended dosages (i.e., single doses >30 mg or cumulative weekly doses >90 mg).1 (See Boxed Warning.)

Withhold alemtuzumab in patients who develop severe cytopenias (except lymphopenia).1 (See Dosage under Dosage and Administration.)

Discontinue therapy permanently in patients with autoimmune hematologic toxicity (i.e., autoimmune anemia or thrombocytopenia) or recurrent or persistent severe cytopenias (except lymphopenia).1 Safety of reinitiating alemtuzumab in patients with autoimmune cytopenia or bone marrow aplasia not established.1

Severe idiopathic thrombocytopenic purpura (ITP), sometimes fatal, reported in 3 patients receiving alemtuzumab in a clinical trial evaluating the drug for treatment of multiple sclerosis.32 Two of these patients received cumulative doses that exceeded the cumulative weekly dose limit.32

Infusion Reactions

Risk of acute infusion reactions, including rigors, fever, bronchospasm, chills, nausea, vomiting, rash, urticaria, dyspnea, and hypotension occurring during or shortly after IV infusion, particularly during first week of therapy.1

Serious, sometimes fatal, infusion-related reactions (e.g., syncope, pulmonary infiltrates, ARDS, respiratory arrest, cardiac arrhythmias, MI, acute cardiac insufficiency, cardiac arrest, angioedema, anaphylactoid shock) reported.1 9

Monitor closely for adverse reactions during and shortly after infusion.1 Withhold alemtuzumab in patients experiencing grade 3 or 4 infusion reactions.1 Initiate medical management (e.g., glucocorticoids, epinephrine, meperidine) as clinically indicated.1

Premedication and incremental dosage escalation used to prevent or ameliorate reactions.1 (See Premedication and also see Dosage under Dosage and Administration.)

Acute systemic injection-related reactions, including fever and chills/rigors, also reported with sub-Q injection of alemtuzumab, but appear to be more common with IV infusion.34 35 36

Immunosuppression

Risk of severe and profound lymphopenia, which increases the potential for tranfusion-associated graft versus host disease (TA-GVHD).1 2 Administer only irradiated blood products unless immediate transfusion is required because of emergency.1

Infectious Complications

Risk of serious (sometimes fatal) opportunistic bacterial, viral, fungal, or protozoan infections resulting from severe and profound lymphopenia.1

Administer prophylactic anti-infectives against Pneumocystis jiroveci (formerly Pneumocystis carinii) and herpesvirus infections during alemtuzumab therapy and for at least 2 months after the last dose of alemtuzumab.1 3 4 (See Anti-infective Prophylaxis under Dosage and Administration.)

Risk of potentially serious or life-threatening CMV infection.1 Monitor patient closely for CMV infection during and for at least 2 months following completion of alemtuzumab therapy.1

If serious infection occurs, temporarily discontinue alemtuzumab;1 reinitiate therapy following resolution of infection.1

Therapy Monitoring

Monitor CBCs and platelet counts weekly during therapy;1 more frequent monitoring may be required in patients with worsening anemia, neutropenia, or thrombocytopenia.1 Following completion of alemtuzumab therapy, monitor CD4+ T-cell counts until levels return to ≥200/mm3.1

Immunization

Avoid immunization with live virus vaccines during therapy with alemtuzumab (safety not established).1

Other Warnings/Precautions

Immunogenicity

Potential of immunogenicity with the use of therapeutic proteins, such as alemtuzumab.1 Development of antibodies to alemtuzumab reported infrequently during clinical trials; antibody development does not appear to affect tumor response.1

Injection Site Reactions

Risk of localized skin and site reactions (e.g., erythema, edema, pruritus, pain) occurring with sub-Q administration, especially during first 1–2 weeks of therapy; may occur more frequently in previously untreated patients.34 35 36

Specific Populations

Pregnancy

Category C.1

Lactation

Not known whether alemtuzumab is distributed into milk;1 however, human IgG distributes into milk.1 Discontinue nursing or the drug.1

Pediatric Use

Safety and efficacy not established.1 5

Geriatric Use

Insufficient experience in patients ≥65 years of age to determine whether geriatric patients respond differently than younger adults.1

Hepatic Impairment

Pharmacokinetics not evaluated.1 Safety and efficacy not established.5

Renal Impairment

Pharmacokinetics not evaluated.1 Safety and efficacy not established.5

Common Adverse Effects

Infusion reactions (pyrexia, chills, hypotension, urticaria, nausea, rash, tachycardia, dyspnea), cytopenias (neutropenia, lymphopenia, thrombocytopenia, anemia), infections (e.g., CMV viremia, CMV infection, other infections), adverse GI effects (nausea, vomiting, diarrhea, abdominal pain), adverse neurologic effects (insomnia, anxiety).1

Interactions for Alemtuzumab

No formal drug interaction studies to date.1 5

Alemtuzumab Pharmacokinetics

Distribution

Extent

Not known whether alemtuzumab crosses the placenta or is distributed into milk;1 however, human IgG crosses the placenta and is distributed into milk.1

Elimination

Elimination Route

Clearance decreases with repeated administration secondary to decreased receptor-mediated clearance (i.e., loss of CD52 receptors in periphery); AUC increases substantially (sevenfold) after 12 weeks of IV dosing in CLL patients receiving recommended dosages.1

Half-life

Mean half-life is 11 hours (range: 2–32 hours) following the first 30-mg IV dose; mean half-life is 6 days (range: 1–14 days) following the last 30-mg IV dose.1

Stability

Storage

Parenteral

Injection Concentrate

2–8°C.1 Do not freeze; if accidentally frozen, thaw at 2–8°C before administration.1 Protect from direct sunlight.1

Following dilution, 15–30°C or under refrigeration (2–8°C); discard after 8 hours.1 5 Protect from light.1

Compatibility

For information on systemic interactions resulting from concomitant use, see Interactions.

No incompatibilities observed between alemtuzumab solution and PVC bags, PVC or polyethylene-lined PVC administration sets.1

Parenteral

Solution Compatibility

Compatible1

Dextrose 5% in water

Sodium chloride 0.9%

Actions

  • An IgG1 kappa immunoglobulin containing human framework (i.e., variable and constant regions) and murine complementarity-determining regions.1 3

  • Binds specifically to antigen CD52 (expressed on the surface of B and T cells; most monocytes, macrophages, and natural killer cells; and a subpopulation of granulocytes),1 2 triggering a host immune response causing lysis of normal and leukemic cells.1 5

  • Mechanism of cell lysis is thought to involve complement-dependent cytotoxicity and antibody-dependent cell-mediated cytotoxicity.1 2

Advice to Patients

  • Risk of hematologic toxicity, infectious complications, and infusion reactions.1 Importance of immediately informing clinician if signs or symptoms of infusion reactions, cytopenias (bleeding, easy bruising, petechiae or purpura, pallor, weakness, or fatigue), or infections (fever) occur.1

  • Advise patients of the importance of taking premedications and prophylactic anti-infectives as prescribed.1

  • Advise patients that irradiation of blood products is required.1

  • Advise patients that they should not be immunized with live viral vaccines if they have recently received treatment with alemtuzumab.1

  • Importance of women informing their clinician if they are or plan to become pregnant or plan to breast-feed.1 Advise women of childbearing potential and men to use effective contraceptive methods during therapy and for at least 6 months following completion of therapy.1

  • Importance of informing clinicians of existing or contemplated therapy, including prescription and OTC drugs and herbal supplements, as well as any concomitant illnesses.1

  • Importance of informing patients of other important precautionary information.1 (See Cautions.)

Preparations

Excipients in commercially available drug preparations may have clinically important effects in some individuals; consult specific product labeling for details.

Alemtuzumab (recombinant DNA origin)

Routes

Dosage Forms

Strengths

Brand Names

Manufacturer

Parenteral

For injection concentrate, for IV infusion

30 mg/mL

Campath

Genzyzme

AHFS DI Essentials. © Copyright, 2004-2014, Selected Revisions December 1, 2010. American Society of Health-System Pharmacists, Inc., 7272 Wisconsin Avenue, Bethesda, Maryland 20814.

† Use is not currently included in the labeling approved by the US Food and Drug Administration.

References

1. Genzyme. Campath (alemtuzumab) prescribing information. Cambridge, MA; 2009 Aug.

2. Flynn JM, Byrd JC. Campath-1H monoclonal antibody therapy. Curr Opin Oncol. 2000; 12:574-81. [PubMed 11085457]

3. Food and Drug Administration. Oncologic drugs advisory committee sixty-sixth meeting. Bethesda, MD; December 2000. From FDA web site.

4. Keating MJ, Flinn I, Jain V et al. Therapeutic role of alemtuzumab (Campath-1H) in patients who have failed fludarabine: results of a large international study. Blood. 2002; 99:3554-61. [IDIS 483673] [PubMed 11986207]

5. Berlex Laboratories, Richmond, CA: Personal communication.

6. Chronic lymphocytic leukemia. From: PDQ. Physician data query (database). Bethesda, MD: National Cancer Institute; 2008 May 16.

7. Food and Drug Administration. Orphan designations pursuant to Section 526 of the Federal Food and Cosmetic Act as amended by the Orphan Drug Act (P.L. 97-414). Rockville, MD; [May 5, 2003]. From FDA web site.

8. Anon. Drugs of choice for cancer. Treat Guidel Med Lett. 2003; 1:41-52. [PubMed 15529105]

9. Food and Drug Administration. MedWatch—Safety-related drug labeling changes: Campath (alemtuzumab) [May 2004]. From FDA web site.

10. Rai KR, Freter CE, Mercier RJ et al. Alemtuzumab in previously treated chronic lymphocytic leukemia patients who also had received fludarabine. J Clin Oncol. 2002; 20:3891-7. [IDIS 492956] [PubMed 12228210]

11. Adult non-Hodgkin’s lymphoma. From: PDQ. Physician data query (database). Bethesda, MD: National Cancer Institute; 2008 Jun 06.

12. Lenihan DJ, Alencar AJ, Yang D et al. Cardiac toxicity of alemtuzumab in patients with mycosis fungoides/Sezary syndrome. Blood. 2004; 104:655-8. [IDIS 520055] [PubMed 15073032]

13. Enblad G, Hagberg H, Erlanson M et al. A pilot study of alemtuzumab (anti-CD52 monoclonal antibody) therapy for patients with relapsed or chemotherapy-refractory peripheral T-cell lymphomas. Blood. 2004; 103:2920-4. [IDIS 515482] [PubMed 15070664]

14. Kennedy GA, Seymour JF, Wolf M et al. Treatment of patients with advanced mycosis fungoides and Sezary syndrome with alemtuzumab. Eur J Haematol. 2003; 71:250-6. [PubMed 12950233]

15. Lundin J, Hagberg H, Repp R et al. Phase 2 study of alemtuzumab (anti-CD52 monoclonal antibody) in patients with advanced mycosis fungoides/Sezary syndrome. Blood. 2003; 101:4267-72. [IDIS 500361] [PubMed 12543862]

16. Uppenkamp M, Engert A, Diehl V et al. Monoclonal antibody therapy with CAMPATH-1H in patients with relapsed high- and low-grade non-Hodgkin’s lymphomas: a multicenter phase I/II study. Ann Hematol. 2002; 81:26-32. [PubMed 11807632]

17. Khorana A, Bunn P, McLaughlin P et al. A phase II multicenter study of CAMPATH-1H antibody in previously treated patients with nonbulky non-Hodgkin’s lymphoma. Leuk Lymphoma. 2001; 41:77-87. [PubMed 11342359]

18. Lundin J, Osterborg A, Brittinger G et al. CAMPATH-1H monoclonal antibody in therapy for previously treated low-grade non-Hodgkin’s lymphomas: a phase II multicenter study. European Study Group of CAMPATH-1H Treatment in Low-Grade Non-Hodgkin’s Lymphoma. J Clin Oncol. 1998; 16:3257-63. [IDIS 414051] [PubMed 9779699]

19. Tang SC, Hewitt K, Reis MD et al. Immunosuppressive toxicity of CAMPATH1H monoclonal antibody in the treatment of patients with recurrent low grade lymphoma. Leuk Lymphoma. 1996; 24:93-101. [PubMed 9049965]

20. Osterborg A, Dyer MJ, Bunjes D et al. Phase II multicenter study of human CD52 antibody in previously treated chronic lymphocytic leukemia. European Study Group of CAMPATH-1H Treatment in Chronic Lymphocytic Leukemia. J Clin Oncol. 1997; 15:1567-74. [IDIS 383720] [PubMed 9193354]

21. Lundin J, Kennedy B, Dearden C et al. No cardiac toxicity associated with alemtuzumab therapy for mycosis fungoides/Sezary syndrome. Blood. 2005; 105:4148-9. [IDIS 535479] [PubMed 15867423]

22. Damaj G, Rubio MT, Audard V et al. Severe cardiac toxicity after monoclonal antibody therapy. Eur J Haematol. 2002; 68:324. [PubMed 12144543]

23. Herbert KE, Prince HM, Westerman DA. Pure red-cell aplasia due to parvovirus B19 infection in a patient treated with alemtuzumab. Blood. 2003; 101:1654. [IDIS 498239] [PubMed 12560244]

24. Crowley B, Woodcock B. Red cell aplasia due to parvovirus b19 in a patient treated with alemtuzumab. Br J Haematol. 2002; 119:279-80. [PubMed 12358942]

25. Pawson R, Dyer MJ, Barge R et al. Treatment of T-cell prolymphocytic leukemia with human CD52 antibody. J Clin Oncol. 1997; 15:2667-72. [IDIS 392532] [PubMed 9215839]

26. Dearden CE, Matutes E, Cazin B et al. High remission rate in T-cell prolymphocytic leukemia with CAMPATH-1H. Blood. 2001; 98:1721-6. [IDIS 469299] [PubMed 11535503]

27. Keating MJ, Cazin B, Coutre S et al. Campath-1H treatment of T-cell prolymphocytic leukemia in patients for whom at least one prior chemotherapy regimen has failed. J Clin Oncol. 2002; 20:205-13. [IDIS 475048] [PubMed 11773171]

28. Dearden CE, Matutes E, Cazin B et al. Very high response rates in previously untreated T-cell prolymphocytic leukaemia patients receiving alemtuzumab (Campath-1H) therapy. Blood. 2003; 102:644a.

29. Polman CH, Uitdehaag BM. New and emerging treatment options for multiple sclerosis. Lancet Neurol. 2003; 2:563-6. [PubMed 12941579]

30. Genzyme Corporation. Fludara plus alemtuzumab (Campath, MabCampath) vs Fludara alone in B-cell chronic lymphocytic leukemia (B-CLL) patients. National Cancer Institute: Clinical Trials (database). Protocol ID: CAM-314. Last accessed: 810/2008.

31. Hillmen P, Skotnicki AB, Robak T et al. Alemtuzumab compared with chlorambucil as first-line therapy for chronic lymphocytic leukemia. J Clin Oncol. 2007; 25:5616-23. [PubMed 17984186]

32. FDA Alert: Alemtuzumab (marketed as Campath). Food and Drug Administration; 2005 Nov 30.(AHFS DI 2007rev: p.10, yellow)

33. Rai KR, Peterson BL, Appelbaum FR et al. Fludarabine compared with chlorambucil as primary therapy for chronic lymphocytic leukemia. N Engl J Med. 2000; 343:1750-7. [IDIS 456744] [PubMed 11114313]

34. Lundin J, Kimby E, Björkholm M et al. Phase II trial of subcutaneous anti-CD52 monoclonal antibody alemtuzumab (Campath-1H) as first-line treatment for patients with B-cell chronic lymphocytic leukemia (B-CLL). Blood. 2002; 100:768-73. [PubMed 12130484]

35. Stilgenbauer S, Zenz T, Winkler D et al. Subcutaneous alemtuzumab in fludarabine-refractory chronic lymphocytic leukemia: clinical results and prognostic marker analyses from the CLL2H study of the German Chronic Lymphocytic Leukemia Study Group. J Clin Oncol. 2009; 27:3994-4001. [PubMed 19597025]

36. Osterborg A, Foà R, Bezares RF et al. Management guidelines for the use of alemtuzumab in chronic lymphocytic leukemia. Leukemia. 2009; 23:1980-8. [PubMed 19626051]

Hide
(web5)