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Infections in Hematology pp 39–47Cite as

Consequences from Specific Treatment Modalities

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Abstract

While the depth and duration of granulocytopenia (neutropenia) represents the most important risk factor for infections in hematologic patients, other treatment- or disease-related aspects of immunosuppression must be taken into consideration. Without wanting to provide an exhaustive review of all these aspects, the following treatment modalities will be addressed here:

  • Purine analogs (fludarabine, cladribine, pentostatin)

  • Monoclonal antibodies to CD20, CD52, and TNF-alpha

Most hematological cancer patients treated with one of these compounds typically receive a combination of these and/or a combination with classical cytostatic drugs. Thus, immunosuppression associated with these treatment modalities will in general be multifactorial, e.g., cellular immunodeficiency plus neutropenia. Moreover, the underlying hematological malignancies by themselves frequently cause immune defects such as granulocytopenia or humoral immunodeficiency. The specific aspects addressed here therefore are mostly additive to the problem of therapy-induced myelosuppression.

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References

  1. Takada K, Danning CL, Kuroiwa T, Schlimgen R, Tassiulas IO, Davis Jr JC, Yarboro CH, Fleisher TA, Boumpas DT, Illei GG. Lymphocyte depletion with fludarabine in patients with psoriatic arthritis: clinical and immunological effects. Ann Rheum Dis. 2003;62:1112–5.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  2. Seymour JF, Kurzrock R, Freireich EJ, Estey EH. 2-Chlorodeoxyadenosine induces durable remissions and prolonged suppression of CD4+ lymphocyte counts in patients with hairy cell leukemia. Blood. 1994;83:2906–11.

    CAS  PubMed  Google Scholar 

  3. Cheson BD. Infections and immunosuppressive complications of purine analog therapy. J Clin Oncol. 1995;13:2431–48.

    CAS  PubMed  Google Scholar 

  4. Anaissie EJ, Kontoyiannis DP, O’Brien S, Kantarjian H, Robertson L, Lerner S, Keating MJ. Infections in patients with chronic lymphocytic leukemia treated with fludarabine. Am J Med. 1998;129:559–66.

    CAS  Google Scholar 

  5. Eichhorst BF, Busch R, Schweighofer C, Wendtner CM, Emmerich B, Hallek M, German CLL Study Group. Due to low infection rates no routine anti-infective prophylaxis is required in younger patients with chronic lymphocytic leukaemia during fludarabine-based first line therapy. Br J Haematol. 2007;136:63–72.

    Article  CAS  PubMed  Google Scholar 

  6. Hensel M, Kornacker M, Yammeni S, Egerer G, Ho AD. Disease activity and pretreatment, rather than hypogammaglobulinaemia, are major risk factors for infectious complications in patients with chronic lymphocytic leukaemia. Br J Haematol. 2003;122:600–6.

    Article  PubMed  Google Scholar 

  7. Tam CS, Seymour JF, Brown M, Campbell P, Scarlett J, Underhill C, Ritchie D, Bond R, Grigg AP. Early and late infectious consequences of adding rituximab to fludarabine and cyclophosphamide in patients with indolent lymphoid malignancies. Haematologica. 2005;90:700–2.

    CAS  PubMed  Google Scholar 

  8. Leporrier M, Chevret S, Cazin B, Boudjerra N, Feugier P, Desablens B, Rapp MJ, Jaubert J, Autrand C, Divine M, Dreyfus B, Maloum K, Travade P, Dighiero G, Binet JL, Chastang C. French Cooperative Group on Chronic Lymphocytic Leukemia. Randomized comparison of fludarabine, CAP, and ChOP in 938 previously untreated stage B and C chronic lymphocytic leukemia patients. Blood. 2001;98:2319–25.

    Article  CAS  PubMed  Google Scholar 

  9. Eichhorst BF, Busch R, Hopfinger G, Pasold R, Hensel M, Steinbrecher C, Siehl S, Jäger U, Bergmann M, Stilgenbauer S, Schweighofer C, Wendtner CM, Döhner H, Brittinger G, Emmerich B, Hallek M German CLL Study Group. Fludarabine plus cyclophosphamide versus fludarabine alone in first-line therapy of younger patients with chronic lymphocytic leukemia. Blood. 2006;107:885–91.

    Article  CAS  PubMed  Google Scholar 

  10. Hallek M, Fischer K, Fingerle-Rowson G, Fink AM, Busch R, Mayer J, Hensel M, Hopfinger G, Hess G, von Grünhagen U, Bergmann M, Catalano J, Zinzani PL, Caligaris-Cappio F, Seymour JF, Berrebi A, Jäger U, Cazin B, Trneny M, Westermann A, Wendtner CM, Eichhorst BF, Staib P, Bühler A, Winkler D, Zenz T, Böttcher S, Ritgen M, Mendila M, Kneba M, Döhner H, Stilgenbauer S. International group of investigators; German chronic lymphocytic leukaemia study group. Addition of rituximab to fludarabine and cyclophosphamide in patients with chronic lymphocytic leukaemia: a randomised, open-label, phase 3 trial. Lancet. 2010;376:1164–74.

    Article  CAS  PubMed  Google Scholar 

  11. Tam CS, Wolf MM, Januszewicz EH, Grigg AP, Prince HM, Westerman D, Seymour JF. A new model for predicting infectious complications during fludarabine-based combination chemotherapy among patients with indolent lymphoid malignancies. Cancer. 2004;101:2042–9.

    Article  CAS  PubMed  Google Scholar 

  12. Nahimana A, Rabodonirina M, Zanetti G, Meneau I, Francioli P, Bille J, Hauser PM. Association between a specific Pneumocystis jiroveci dihydropteroate synthase mutation and failure of pyrimethamine/sulfadoxine prophylaxis in human immunodeficiency virus-positive and -negative patients. J Infect Dis. 2003;188:1017–23.

    Article  CAS  PubMed  Google Scholar 

  13. Stein CR. Sulfa use, dihydropteroate synthase mutations, and Pneumocystis jirovecii pneumonia. Emerg Infect Dis. 2004;10:1760–5.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  14. Tsiodras S, Samonis G, Keating MJ, Kontoyiannis DP. Infection and immunity in chronic lymphocytic leukemia. Mayo Clin Proc. 2000;75:1039–54.

    Article  CAS  PubMed  Google Scholar 

  15. Colangelo G, Baughman RP, Dohn MN, Frame PT. Follow-up bronchoalveolar lavage in AIDS patients with Pneumocystis carinii pneumonia. Pneumocystis carinii burden predicts early relapse. Am Rev Respir Dis. 1991;143:1067–71.

    Article  CAS  PubMed  Google Scholar 

  16. Coiffier B, Lepage E, Brière J, Herbrecht R, Tilly H, Bouabdallah R, Morel P, van den Neste E, Salles G, Gaulard P, Reyes F, Gisselbrecht C. CHOP chemotherapy plus rituximab compared with CHOP alone in elderly patients with diffuse large-B-cell lymphoma. N Engl J Med. 2002;346:235–42.

    Article  CAS  PubMed  Google Scholar 

  17. Vidal L, Gafter-Gvili A, Leibovici L, Dreyling M, Ghielmini M, Hsu Schmitz SF, Cohen A, Shpilberg O. Rituximab maintenance for the treatment of patients with follicular lymphoma: systematic review and meta-analysis of randomized trials. J Natl Cancer Inst. 2009;101:248–55.

    Article  CAS  PubMed  Google Scholar 

  18. Salles G, Seymour JF, Offner F, López-Guillermo A, Belada D, Xerri L, Feugier P, Bouabdallah R, Catalano JV, Brice P, Caballero D, Haioun C, Pedersen LM, Delmer A, Simpson D, Leppa S, Soubeyran P, Hagenbeek A, Casasnovas O, Intragumtornchai T, Fermé C, da Silva MG, Sebban C, Lister A, Estell JA, Milone G, Sonet A, Mendila M, Coiffier B, Tilly H. Rituximab maintenance for 2 years in patients with high tumour burden follicular lymphoma responding to rituximab plus chemotherapy (PRIMA): a phase 3, randomised controlled trial. Lancet. 2011;377:42–51.

    Article  CAS  PubMed  Google Scholar 

  19. Yeo W, Chan TC, Leung NW, Lam WY, Mo FK, Chu MT, Chan HL, Hui EP, Lei KI, Mok TS, Chan PK. Hepatitis B virus reactivation in lymphoma patients with prior resolved hepatitis B undergoing anticancer therapy with or without rituximab. J Clin Oncol. 2009;27:605–11.

    Article  CAS  PubMed  Google Scholar 

  20. Evens AM, Jovanovic BD, Su YC, Raisch DW, Ganger D, Belknap SM, Dai MS, Chiu BC, Fintel B, Cheng Y, Chuang SS, Lee MY, Chen TY, Lin SF, Kuo CY. Rituximab-associated hepatitis B virus (HBV) reactivation in lymphoproliferative diseases: meta-analysis and examination of FDA safety reports. Ann Oncol. 2011;22:1170–80.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  21. Ennishi D, Maeda Y, Niitsu N, Kojima M, Izutsu K, Takizawa J, Kusumoto S, Okamoto M, Yokoyama M, Takamatsu Y, Sunami K, Miyata A, Murayama K, Sakai A, Matsumoto M, Shinagawa K, Takaki A, Matsuo K, Kinoshita T, Tanimoto M. Hepatic toxicity and prognosis in hepatitis C virus-infected patients with diffuse large B-cell lymphoma treated with rituximab-containing chemotherapy regimens: a Japanese multicenter analysis. Blood. 2010;116:5119–25.

    Article  CAS  PubMed  Google Scholar 

  22. Zurawska U, Hicks LK, Woo G, Bell CM, Krahn M, Chan KK, Feld JJ. Hepatitis B virus screening before chemotherapy for lymphoma: a cost-effectiveness analysis. J Clin Oncol. 2012;30:3167–73.

    Article  PubMed  Google Scholar 

  23. Carson KR, Evens AM, Richey EA, Habermann TM, Focosi D, Seymour JF, Laubach J, Bawn SD, Gordon LI, Winter JN, Furman RR, Vose JM, Zelenetz AD, Mamtani R, Raisch DW, Dorshimer GW, Rosen ST, Muro K, Gottardi-Littell NR, Talley RL, Sartor O, Green D, Major EO, Bennett CL. Progressive multifocal leukoencephalopathy after rituximab therapy in HIV-negative patients: a report of 57 cases from the research on adverse drug events and reports project. Blood. 2009;113:4834–40.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  24. Nosari A, Tedeschi A, Ricci F, Montillo M. Characteristics and stage of the underlying diseases could determine the risk of opportunistic infections in patients receiving alemtuzumab. Haematologica. 2008;93:e30–1.

    Article  CAS  PubMed  Google Scholar 

  25. Lundin J, Kimby E, Bjorkholm M, Lundin J, Kimby E, Björkholm M, Broliden PA, Celsing F, Hjalmar V, Mollgard L, Rebello P, Hale G, Waldmann H, Mellstedt H, Österborg A. Phase II trial of subcutaneous anti-CD52 monoclonal antibody alemtuzumab (Campath-1H) as first-line treatment for patients with Bcell chronic lymphocytic leukemia (B-CLL). Blood. 2002;100:768–73.

    Article  CAS  PubMed  Google Scholar 

  26. Keating MJ, Flinn I, Jain V, Binet JL, Hillmen P, Byrd J, Albitar M, Brettman L, Santabarbara P, Wacker B, Rai KR. Therapeutic role of alemtuzumab (Campath-1H) in patients who have failed fludarabine: results of a large international study. Blood. 2002;99:3554–61.

    Article  CAS  PubMed  Google Scholar 

  27. Thursky KA, Worth LJ, Seymour JF, Thursky KA, Worth LJ, Seymour JF, Miles Prince H, Slavin MA. Spectrum of infection, risk and recommendations for prophylaxis and screening among patients with lymphoproliferative disorders treated with alemtuzumab. Br J Haematol. 2006;132:3–12.

    Article  PubMed  Google Scholar 

  28. Martin SI, Marty FM, Fiumara K, Treon SP, Gribben JG, Baden LR. Infectious complications associated with alemtuzumab use for lymphoproliferative disorders. Clin Infect Dis. 2006;43:16–24.

    Article  CAS  PubMed  Google Scholar 

  29. Lin TS, Donohue KA, Byrd JC, Lucas MS, Hoke EE, Bengtson EM, Rai KR, Atkins JN, Link BK, Larson RA. Consolidation therapy with subcutaneous alemtuzumab after fludarabine and rituximab induction therapy for previously untreated chronic lymphocytic leukemia: final analysis of CALGB 10101. J Clin Oncol. 2010;28:4500–6.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  30. Wendtner CM, Ritgen M, Schweighofer CD, Wendtner CM, Ritgen M, Schweighofer CD, Fingerle-Rowson G, Campe H, Jäger G, Eichhorst B, Busch R, Diem H, Engert A, Stilgenbauer S, Döhner H, Kneba M, Emmerich B, Hallek M German CLL Study Group. 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). Leukemia. 2004;18:1093–101.

    Article  CAS  PubMed  Google Scholar 

  31. Österborg A, Foa R, Bezares RF, Dearden C, Dyer MJ, Geisler C, Lin TS, Montillo M, van Oers MH, Wendtner CM, Rai KR. Management guidelines for the use of alemtuzumab in chronic lymphocytic leukemia. Leukemia. 2009;23:1980–8.

    Article  PubMed  Google Scholar 

  32. Desoubeaux G, Caumont C, Passot C, Dartigeas C, Bailly E, Chandenier J, Duong TH. Two cases of opportunistic parasite infections in patients receiving alemtuzumab. J Clin Pathol. 2012;65:92–5.

    Article  PubMed  Google Scholar 

  33. Tsiodras S, Samonis G, Boumpas DT, Kontoyiannis DP. Fungal infections complicating tumor necrosis factor alpha blockade therapy. Mayo Clin Proc. 2008;83:181–94.

    Article  CAS  PubMed  Google Scholar 

  34. Couriel D, Saliba R, Hicks K, Ippoliti C, de Lima M, Hosing C, Khouri I, Andersson B, Gajewski J, Donato M, Anderlini P, Kontoyiannis DP, Cohen A, Martin T, Giralt S, Champlin R. Tumor necrosis factor-alpha blockade for the treatment of acute GVHD. Blood. 2004;104:649–54.

    Article  CAS  PubMed  Google Scholar 

  35. Alousi AM, Weisdorf DJ, Logan BR, Bolaños-Meade J, Carter S, Difronzo N, Pasquini M, Goldstein SC, Ho VT, Hayes-Lattin B, Wingard JR, Horowitz MM, Levine JE. Etanercept, mycophenolate, denileukin, or pentostatin plus corticosteroids for acute graft-versus-host disease: a randomized phase 2 trial from the blood and marrow transplant clinical trials network. Blood. 2009;114:511–7.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  36. Levine JE, Paczesny S, Mineishi S, Braun T, Choi SW, Hutchinson RJ, Jones D, Khaled Y, Kitko CL, Bickley D, Krijanovski O, Reddy P, Yanik G, Ferrara JL. Etanercept plus methylprednisolone as initial therapy for acute graft-versus-host disease. Blood. 2008;111:2470–5.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  37. Busca A, Locatelli F, Marmont F, Ceretto C, Falda M. Recombinant human soluble tumor necrosis factor receptor fusion protein as treatment for steroid refractory graft-versus-host disease following allogeneic hematopoietic stem cell transplantation. Am J Hematol. 2007;82:45–52.

    Article  CAS  PubMed  Google Scholar 

  38. Hamadani M, Hofmeister CC, Jansak B, Phillips G, Elder P, Blum W, Penza S, Lin TS, Klisovic R, Marcucci G, Farag SS, Devine SM. Addition of infliximab to standard acute graft-versus-host disease prophylaxis following allogeneic peripheral blood cell transplantation. Biol Blood Marrow Transplant. 2008;14:783–9.

    Article  PubMed Central  PubMed  Google Scholar 

  39. Marty FM, Lee SJ, Fahey MM, et al. Infliximab use in patients with severe graft-versus-host disease and other emerging risk factors of non-Candida invasive fungal infections in allogeneic hematopoietic stem cell transplant recipients: a cohort study. Blood. 2003;102:2768–76.

    Article  CAS  PubMed  Google Scholar 

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Authors and Affiliations

  1. Department of Hematology, Oncology and Palliative Care, Klinikum Ernst von Bergmann, Charlottenstrasse 72, D-14467, Potsdam, Germany

    Georg Maschmeyer

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  1. Georg Maschmeyer
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Correspondence to Georg Maschmeyer .

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Editors and Affiliations

  1. Department of Hematology, Oncology and Palliative Care, Klinikum Ernst von Bergmann, Potsdam, Germany

    Georg Maschmeyer

  2. Department of Infectious Diseases, Infection Control and Employee Health, M.D. Anderson Cancer Center University of Texas, Houston, Texas, USA

    Kenneth V.I. Rolston

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Maschmeyer, G. (2015). Consequences from Specific Treatment Modalities. In: Maschmeyer, G., Rolston, K. (eds) Infections in Hematology. Springer, Berlin, Heidelberg. https://doi.org/10.1007/978-3-662-44000-1_3

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  • DOI: https://doi.org/10.1007/978-3-662-44000-1_3

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