Spectrum of infection, risk and recommendations for prophylaxis and screening among patients with lymphoproliferative disorders treated with alemtuzumab *

There is an increasing use of monoclonal antibodies in the treatment of haematological malignancies. Alemtuzumab (Campath‐1H; Ilex Pharmaceuticals, San Antonio, TX, USA) is a monoclonal antibody reactive with the CD52 antigen used as first and second line therapy for two types of lymphoproliferative disorders: chronic lymphocytic leukaemia (CLL), and T‐cell lymphomas [both peripheral (PTCL) and cutaneous (CTCL)]. With alemtuzumab therapy, viral, bacterial and fungal infectious complications are frequent, and may be life threatening. An understanding of the patients at highest risk and duration of risk are important in developing recommendations for empirical management, antimicrobial prophylaxis and targeted surveillance. This review discusses the infection risks associated with these lymphoproliferative disorders and their treatment, and provide detailed recommendations for screening and prophylaxis.

[1]  E. Giné,et al.  Combination Chemotherapy with Fludarabine, Cyclophosphamide and Mitoxantrone (FCM) Induces a High Response Rate in Previously Untreated CLL. , 2005 .

[2]  Haralampos J. Milionis,et al.  Cutaneous T-cell lymphoma. , 2005, The Journal of dermatologic surgery and oncology.

[3]  S. Grossman,et al.  Primary brain tumors treated with steroids and radiotherapy: low CD4 counts and risk of infection. , 2005, International journal of radiation oncology, biology, physics.

[4]  M. Grever,et al.  Filgrastim and alemtuzumab (Campath-1H) for refractory chronic lymphocytic leukemia , 2005, Leukemia.

[5]  J. Seymour,et al.  Severe and prolonged myeloid haematopoietic toxicity with myelodysplastic features following alemtuzumab therapy in patients with peripheral T‐cell lymphoproliferative disorders , 2005, British journal of haematology.

[6]  M. Andreeff,et al.  Early results of a chemoimmunotherapy regimen of fludarabine, cyclophosphamide, and rituximab as initial therapy for chronic lymphocytic leukemia. , 2005, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[7]  Russell E. Lewis,et al.  Zygomycosis in a tertiary-care cancer center in the era of Aspergillus-active antifungal therapy: a case-control observational study of 27 recent cases. , 2005, The Journal of infectious diseases.

[8]  E. Iannitto,et al.  Hepatitis B virus reactivation and alemtuzumab therapy , 2005, European journal of haematology.

[9]  J. Wingard The changing face of invasive fungal infections in hematopoietic cell transplant recipients , 2005, Current opinion in oncology.

[10]  W. Kern Outpatient management in patients with neutropenia after intensive chemotherapy--is it safe? , 2005, Annals of oncology : official journal of the European Society for Medical Oncology.

[11]  H. Prince,et al.  Alemtuzumab: effective monotherapy for simultaneous B‐cell chronic lymphocytic leukaemia and Sézary syndrome , 2004, European journal of haematology.

[12]  Ashley P Ng,et al.  Incidence, Natural History and Management of Cytomegalovirus (CMV) Dnaemia and Disease in Patients with Haematological Malignancies in the Non-Allogeneic Transplantation Setting. , 2004 .

[13]  C. Tam,et al.  A new model for predicting infectious complications during fludarabine‐based combination chemotherapy among patients with indolent lymphoid malignancies , 2004, Cancer.

[14]  J. Englund,et al.  Breakthrough fungal infections in stem cell transplant recipients receiving voriconazole. , 2004, Clinical infectious diseases : an official publication of the Infectious Diseases Society of America.

[15]  A. Favero,et al.  Toxoplasma gondii infection in patients with hematological malignancies , 2004, Annals of Hematology.

[16]  H. Döhner,et al.  Consolidation with alemtuzumab in patients with chronic lymphocytic leukemia (CLL) in first remission – experience on safety and efficacy within a randomized multicenter phase III trial of the German CLL Study Group (GCLLSG) , 2004, Leukemia.

[17]  C. Fegan,et al.  Guidelines on the diagnosis and management of chronic lymphocytic leukaemia , 2004, British journal of haematology.

[18]  M. Erlanson,et al.  A pilot study of alemtuzumab (anti-CD52 monoclonal antibody) therapy for patients with relapsed or chemotherapy-refractory peripheral T-cell lymphomas. , 2004, Blood.

[19]  S. Richards,et al.  Early prediction of outcome and response to alemtuzumab therapy in chronic lymphocytic leukemia. , 2004, Blood.

[20]  E. Kimby,et al.  Cellular immune reconstitution after subcutaneous alemtuzumab (anti-CD52 monoclonal antibody, CAMPATH-1H) treatment as first-line therapy for B-cell chronic lymphocytic leukaemia , 2004, Leukemia.

[21]  J. Byrd,et al.  Management guidelines for use of alemtuzumab in B-cell chronic lymphocytic leukemia. , 2004, Clinical lymphoma.

[22]  M. Asaka,et al.  Hepatitis B Virus Reactivation in a Case of Non-Hodgkin's Lymphoma Treated with Chemotherapy and Rituximab: Necessity of Prophylaxis for Hepatitis B Virus Reactivation in Rituximab Therapy , 2004, Leukemia & lymphoma.

[23]  E. Thiel,et al.  Efficacy and Tolerability of Alemtuzumab (CAMPATH-1H) in the Salvage Treatment of B-Cell Chronic Lymphocytic Leukemia—Change of Regimen Needed? , 2004, Leukemia & lymphoma.

[24]  G. Mufti,et al.  BEAM-alemtuzumab reduced-intensity allogeneic stem cell transplantation for lymphoproliferative diseases: GVHD, toxicity, and survival in 65 patients. , 2004, Blood.

[25]  O. Sezer,et al.  Treatment of refractory chronic lymphocytic leukemia with Campath‐1H in combination with lamivudine in chronic hepatitis B infection , 2004, European journal of haematology.

[26]  H. Kantarjian,et al.  Alemtuzumab as treatment for residual disease after chemotherapy in patients with chronic lymphocytic leukemia , 2003, Cancer.

[27]  V. Pitini,et al.  Disseminated molluscum contagiosum in a patient with chronic lymphocytic leukaemia after alemtuzumab , 2003, British journal of haematology.

[28]  H. Prince,et al.  Treatment of patients with advanced mycosis fungoides and Sézary syndrome with alemtuzumab , 2003, European journal of haematology.

[29]  D. Bouscary,et al.  Tuberculosis due to Mycobacterium bovis after alemtuzumab administration. , 2003, Clinical infectious diseases : an official publication of the Infectious Diseases Society of America.

[30]  G. Lau,et al.  Hepatitis virus infections in patients with cancer , 2003 .

[31]  E. Anaissie,et al.  Infections in chronic leukemias and other hematological malignancies , 2003 .

[32]  P. Chandrasekar Fungi other than Candida and Aspergillus , 2003 .

[33]  T. Walsh,et al.  Management strategies for infections caused by Candida species , 2003 .

[34]  G. Juliusson,et al.  Phase 2 study of alemtuzumab (anti-CD52 monoclonal antibody) in patients with advanced mycosis fungoides/Sezary syndrome. , 2003, Blood.

[35]  H. Prince,et al.  Pure red-cell aplasia due to parvovirus B19 infection in a patient treated with alemtuzumab. , 2003, Blood.

[36]  G. Mazurek,et al.  Guidelines for using the QuantiFERON-TB test for diagnosing latent Mycobacterium tuberculosis infection. Centers for Disease Control and Prevention. , 2003, MMWR. Recommendations and reports : Morbidity and mortality weekly report. Recommendations and reports.

[37]  M. Enomoto,et al.  Pulmonary nocardiosis with bilateral diffuse granular lung shadows in a patient with subcutaneous panniculitic T-cell lymphoma. , 2002, Internal medicine.

[38]  R. Mercier,et al.  Alemtuzumab in previously treated chronic lymphocytic leukemia patients who also had received fludarabine. , 2002, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[39]  Keiji Fukuda,et al.  Guidelines for preventing opportunistic infections among HIV-infected persons - 2002 , 2002 .

[40]  S. Coutre,et al.  Cytomegalovirus viremia during Campath-1H therapy for relapsed and refractory chronic lymphocytic leukemia and prolymphocytic leukemia. , 2002, Clinical lymphoma.

[41]  E. Kimby,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). , 2002, Blood.

[42]  K. Holmes,et al.  Guidelines for preventing opportunistic infections among HIV-infected persons--2002. Recommendations of the U.S. Public Health Service and the Infectious Diseases Society of America. , 2002, MMWR. Recommendations and reports : Morbidity and mortality weekly report. Recommendations and reports.

[43]  H. Kelly,et al.  Chronic Strongyloides stercoralis infection in Laotian immigrants and refugees 7–20 years after resettlement in Australia , 2002, Epidemiology and Infection.

[44]  J. Byrd,et al.  Therapeutic role of alemtuzumab (Campath-1H) in patients who have failed fludarabine: results of a large international study. , 2002, Blood.

[45]  J. Manning,et al.  Epstein–Barr Virus-Positive B-Cell Lymphoproliferative Disorders Arising in Immunodeficient Patients Previously Treated With Fludarabine for Low-Grade B-Cell Neoplasms , 2002, The American journal of surgical pathology.

[46]  J. Byrd,et al.  Frequency and type of serious infections in fludarabine‐refractory B‐cell chronic lymphocytic leukemia and small lymphocytic lymphoma , 2002, Cancer.

[47]  D. Catovsky,et al.  High remission rate in T-cell prolymphocytic leukemia with CAMPATH-1H. , 2001, Blood.

[48]  R. Larson,et al.  Impact of therapy With chlorambucil, fludarabine, or fludarabine plus chlorambucil on infections in patients with chronic lymphocytic leukemia: Intergroup Study Cancer and Leukemia Group B 9011. , 2001, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[49]  P. Ljungman,et al.  Prophylactic measures in the solid-organ recipient before transplantation. , 2001, Clinical infectious diseases : an official publication of the Infectious Diseases Society of America.

[50]  J. Greene,et al.  Infectious complications of cutaneous t-cell lymphoma. , 2001, Cancer control : journal of the Moffitt Cancer Center.

[51]  H. Kantarjian,et al.  Results of the fludarabine and cyclophosphamide combination regimen in chronic lymphocytic leukemia. , 2001, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[52]  R. Garland,et al.  Peripheral blood CD4 + T-lymphocyte counts during Pneumocystis carinii pneumonia in immunocompromised patients without HIV infection. , 2000, Chest.

[53]  H. Prentice,et al.  Towards a targeted, risk‐based, antifungal strategy in neutropenic patients , 2000, British journal of haematology.

[54]  G. Sarosi,et al.  Practice guidelines for the management of patients with histoplasmosis. Infectious Diseases Society of America. , 2000, Clinical infectious diseases : an official publication of the Infectious Diseases Society of America.

[55]  G. Campbell,et al.  Practice guidelines for the management of patients with blastomycosis. Infectious Diseases Society of America. , 2000, Clinical infectious diseases : an official publication of the Infectious Diseases Society of America.

[56]  Paul L. Williams,et al.  Practice Guidelines for the Treatment of Coccidioidomycosis , 2000 .

[57]  C. Mackall T‐Cell Immunodeficiency Following Cytotoxic Antineoplastic Therapy: A Review , 2000, The oncologist.

[58]  S. Crawford,et al.  High rates of Pneumocystis carinii pneumonia in allogeneic blood and marrow transplant recipients receiving dapsone prophylaxis. , 1999, Clinical infectious diseases : an official publication of the Infectious Diseases Society of America.

[59]  F. Foss,et al.  Chemotherapy with etoposide, vincristine, doxorubicin, bolus cyclophosphamide, and oral prednisone in patients with refractory cutaneous T‐cell lymphoma , 1999, Cancer.

[60]  J. Fishman,et al.  A prospective randomized trial comparing the toxicity and safety of atovaquone with trimethoprim/sulfamethoxazole as Pneumocystis carinii pneumonia prophylaxis following autologous peripheral blood stem cell transplantation , 1999, Bone Marrow Transplantation.

[61]  E. Anaissie,et al.  Infections in Patients with Chronic Lymphocytic Leukemia Treated with Fludarabine , 1998, Annals of Internal Medicine.

[62]  E J Freireich,et al.  Long-term follow-up of patients with chronic lymphocytic leukemia (CLL) receiving fludarabine regimens as initial therapy. , 1998, Blood.

[63]  L. Ginaldi,et al.  Levels of expression of CD52 in normal and leukemic B and T cells: correlation with in vivo therapeutic responses to Campath-1H. , 1998, Leukemia research.

[64]  B. Marsh Infectious complications of human T cell leukemia/lymphoma virus type I infection. , 1996, Clinical infectious diseases : an official publication of the Infectious Diseases Society of America.

[65]  M. Urowitz,et al.  CAMPATH-1H, a humanized monoclonal antibody, in refractory rheumatoid arthritis. An intravenous dose-escalation study. , 1995, Arthritis and rheumatism.

[66]  R. Hackman,et al.  Toxoplasma gondii infection in marrow transplant recipients: a 20 year experience. , 1994, Bone marrow transplantation.

[67]  J. Salisbury,et al.  Immunohistochemical analysis of CDw52 antigen expression in non-Hodgkin's lymphomas. , 1994, Journal of clinical pathology.

[68]  S. Molica,et al.  Infections in chronic lymphocytic leukemia. Analysis of incidence as a function of length of follow-up. , 1993, Haematologica.

[69]  E. Vonderheid,et al.  Infections complicating mycosis fungoides and Sézary syndrome. , 1992, JAMA.

[70]  R. Woolson,et al.  Risk factors for hospital-acquired candidemia. A matched case-control study. , 1989, Archives of internal medicine.

[71]  F. Ognibene,et al.  CD4 counts as predictors of opportunistic pneumonias in human immunodeficiency virus (HIV) infection. , 1989, Annals of internal medicine.

[72]  P. Bunn,et al.  Septicemic complications of the cutaneous T-cell lymphomas. , 1981, The American journal of medicine.

[73]  J. Enders,et al.  Infectious Diseases Society of America. , 1969, Antimicrobial agents and chemotherapy.

[74]  S. Pileri,et al.  Preliminary observations of a phase II study of reduced-dose alemtuzumab treatment in patients with pretreated T-cell lymphoma. , 2005, Haematologica.

[75]  C. Tam,et al.  Early and late infectious consequences of adding rituximab to fludarabine and cyclophosphamide in patients with indolent lymphoid malignancies. , 2005, Haematologica.

[76]  M. Hallek,et al.  Fludarabine plus cyclophosphamide (FC) induces higher remission rates and longer progression free survival (PFS) than fludarabine (F) alone in first line therapy of younger patients (PTS) with chronic lymphocytic leukemia (CLL): Results of a phase III stu , 2005 .

[77]  P. Chiusolo,et al.  Cytomegalovirus reactivation during alemtuzumab therapy for chronic lymphocytic leukemia: incidence and treatment with oral ganciclovir. , 2004, Haematologica.

[78]  A. Nosari,et al.  Infectious toxicity using alemtuzumab. , 2004, Haematologica.

[79]  R. Price,et al.  Prevention of opportunistic infections in immunosuppressed patients in the tropical top end of the Northern Territory. , 2003, Communicable diseases intelligence quarterly report.

[80]  D. Catovsky,et al.  Alemtuzumab in T-cell malignancies , 2002, Medical oncology.

[81]  P. Hillmen,et al.  Immunological effects and safe administration of alemtuzumab (MabCampath™) in advanced B-CLL , 2002, Medical oncology.

[82]  M. Kalin,et al.  Fatal adenovirus infection during alemtuzumab (anti-CD52 monoclonal antibody) treatment of a patient with fludarabine-refractory B-CELL chronic lymphocytic leukemia , 2002, Medical oncology.

[83]  Mmwr Dispatch Guidelines for Using the QuantiFERON ®-TB Test for Diagnosing Latent Mycobacterium tuberculosis Infection , 2002 .

[84]  M. Vasconcelles,et al.  Aerosolized pentamidine as pneumocystis prophylaxis after bone marrow transplantation is inferior to other regimens and is associated with decreased survival and an increased risk of other infections. , 2000, Biology of blood and marrow transplantation : journal of the American Society for Blood and Marrow Transplantation.

[85]  N. Ampel,et al.  Practice guideline for the treatment of coccidioidomycosis. Infectious Diseases Society of America. , 2000, Clinical infectious diseases : an official publication of the Infectious Diseases Society of America.