Hematopoietic support after hematopoietic cell transplantation
- Robert S Negrin, MD
Robert S Negrin, MD
- Section Editor — Bone Marrow Transplantation
- Professor of Medicine
- Stanford University School of Medicine
Autologous and allogeneic hematopoietic cell transplantation (HCT) are associated with neutropenia, anemia, and thrombocytopenia in the peri-transplant period. The degree of myelosuppression and the time to hematopoietic recovery differ with multiple factors including the preparative regimen and graft source. Blood product transfusions and hematopoietic growth factors are essential components of transplant care.
The term "hematopoietic cell transplantation" will be used throughout this review as a general term to cover transplantation of progenitor cells from any source (eg, bone marrow, peripheral blood, umbilical cord blood). Otherwise, the source of such cells will be specified (eg, autologous PBPC transplantation).
Hematopoietic support after HCT will be discussed here. Other supportive care issues surrounding HCT are presented separately, as is quality of life following HCT and acute and chronic graft-versus-host disease (See "Management of the hematopoietic cell transplant recipient in the immediate post-transplant period" and "Quality of life following hematopoietic cell transplantation" and "Prevention of acute graft-versus-host disease" and "Treatment of chronic graft-versus-host disease".)
The diagnosis and treatment of pulmonary, renal, and infectious complications following HCT are also presented separately. (See "Pulmonary complications after allogeneic hematopoietic cell transplantation" and "Pulmonary complications after autologous hematopoietic cell transplantation" and "Kidney disease following hematopoietic cell transplantation" and "Overview of infections following hematopoietic cell transplantation".)
BLOOD PRODUCT SUPPORT
Blood product support is usually required before, during, and following hematopoietic cell transplantation (HCT) . In addition, blood product support, with resulting iron overload, is commonly seen in those patients undergoing HCT for a hematologic disorder. Such iron overload (eg, serum ferritin >1000 ng/mL) may adversely affect overall survival post-HCT, increasing the likelihood of acute graft-versus-host disease, as well as the incidence of blood stream infections and sinusoidal obstruction syndrome of the liver [2-4].To continue reading this article, you must log in with your personal, hospital, or group practice subscription. For more information on subscription options, click below on the option that best describes you:
- Gajewski JL, Johnson VV, Sandler SG, et al. A review of transfusion practice before, during, and after hematopoietic progenitor cell transplantation. Blood 2008; 112:3036.
- Pullarkat V, Blanchard S, Tegtmeier B, et al. Iron overload adversely affects outcome of allogeneic hematopoietic cell transplantation. Bone Marrow Transplant 2008; 42:799.
- Maradei SC, Maiolino A, de Azevedo AM, et al. Serum ferritin as risk factor for sinusoidal obstruction syndrome of the liver in patients undergoing hematopoietic stem cell transplantation. Blood 2009; 114:1270.
- Mahindra A, Bolwell B, Sobecks R, et al. Elevated pretransplant ferritin is associated with a lower incidence of chronic graft-versus-host disease and inferior survival after myeloablative allogeneic haematopoietic stem cell transplantation. Br J Haematol 2009; 146:310.
- Avery RK, Adal KA, Longworth DL, Bolwell BJ. A survey of allogeneic bone marrow transplant programs in the United States regarding cytomegalovirus prophylaxis and pre-emptive therapy. Bone Marrow Transplant 2000; 26:763.
- Schiffer CA, Anderson KC, Bennett CL, et al. Platelet transfusion for patients with cancer: clinical practice guidelines of the American Society of Clinical Oncology. J Clin Oncol 2001; 19:1519.
- Wandt H, Schaefer-Eckart K, Wendelin K, et al. Therapeutic platelet transfusion versus routine prophylactic transfusion in patients with haematological malignancies: an open-label, multicentre, randomised study. Lancet 2012; 380:1309.
- A Randomised Controlled Trial of Prophylactic Vs No-Prophylactic Platelet Transfusions in Patients with Haematological Malignancies (TOPPS: Trial Of Prophylactic PlateletS) http://public.ukcrn.org.uk/Search/StudyDetail.aspx?StudyID=3825 (Accessed on August 21, 2012).
- Stanworth SJ, Dyer C, Choo L, et al. Do all patients with hematologic malignancies and severe thrombocytopenia need prophylactic platelet transfusions? Background, rationale, and design of a clinical trial (trial of platelet prophylaxis) to assess the effectiveness of prophylactic platelet transfusions. Transfus Med Rev 2010; 24:163.
- Stanworth SJ, Estcourt LJ, Powter G, et al. A no-prophylaxis platelet-transfusion strategy for hematologic cancers. N Engl J Med 2013; 368:1771.
- Simon J. Stanworth, Lise Estcourt, Gillian Powter, et al. The Effect of a No-Prophylactic Versus Prophylactic Platelet Transfusion Strategy On Bleeding in Patients with Hematological Malignancies and Severe Thrombocytopenia (TOPPS trial). A Randomized Controlled, Non-Inferiority Trial. American Society of Hematology abstract book 2012; 120:1.
- Bernstein SH, Nademanee AP, Vose JM, et al. A multicenter study of platelet recovery and utilization in patients after myeloablative therapy and hematopoietic stem cell transplantation. Blood 1998; 91:3509.
- Dominietto A, Raiola AM, van Lint MT, et al. Factors influencing haematological recovery after allogeneic haemopoietic stem cell transplants: graft-versus-host disease, donor type, cytomegalovirus infections and cell dose. Br J Haematol 2001; 112:219.
- Rebulla P, Finazzi G, Marangoni F, et al. The threshold for prophylactic platelet transfusion in adults with acute myeloid leukemia. N Eng J Med 1997; 337:1870.
- Heckman KD, Weiner GJ, Davis CS, et al. Randomized study of prophylactic platelet transfusion threshold during induction therapy for adult acute leukemia: 10,000/microL versus 20,000/microL. J Clin Oncol 1997; 15:1143.
- Diedrich B, Remberger M, Shanwell A, et al. A prospective randomized trial of a prophylactic platelet transfusion trigger of 10 x 10(9) per L versus 30 x 10(9) per L in allogeneic hematopoietic progenitor cell transplant recipients. Transfusion 2005; 45:1064.
- Schmitz N, Linch DC, Dreger P, et al. Randomised trial of filgrastim-mobilised peripheral blood progenitor cell transplantation versus autologous bone-marrow transplantation in lymphoma patients. Lancet 1996; 347:353.
- Smith TJ, Bohlke K, Lyman GH, et al. Recommendations for the Use of WBC Growth Factors: American Society of Clinical Oncology Clinical Practice Guideline Update. J Clin Oncol 2015; 33:3199.
- Paul M, Ram R, Kugler E, et al. Subcutaneous versus intravenous granulocyte colony stimulating factor for the treatment of neutropenia in hospitalized hemato-oncological patients: randomized controlled trial. Am J Hematol 2014; 89:243.
- Dekker A, Bulley S, Beyene J, et al. Meta-analysis of randomized controlled trials of prophylactic granulocyte colony-stimulating factor and granulocyte-macrophage colony-stimulating factor after autologous and allogeneic stem cell transplantation. J Clin Oncol 2006; 24:5207.
- Ringdén O, Labopin M, Gorin NC, et al. Treatment with granulocyte colony-stimulating factor after allogeneic bone marrow transplantation for acute leukemia increases the risk of graft-versus-host disease and death: a study from the Acute Leukemia Working Party of the European Group for Blood and Marrow Transplantation. J Clin Oncol 2004; 22:416.
- Appelbaum FR. Use of granulocyte colony-stimulating factor following hematopoietic cell transplantation: does haste make waste? J Clin Oncol 2004; 22:390.
- Link H, Boogaerts MA, Carella AM, et al. A controlled trial of recombinant human granulocyte-macrophage colony-stimulating factor after total body irradiation, high-dose chemotherapy, and autologous bone marrow transplantation for acute lymphoblastic leukemia or malignant lymphoma. Blood 1992; 80:2188.
- Advani R, Chao NJ, Horning SJ, et al. Granulocyte-macrophage colony-stimulating factor (GM-CSF) as an adjunct to autologous hemopoietic stem cell transplantation for lymphoma. Ann Intern Med 1992; 116:183.
- Gorin NC, Coiffier B, Hayat M, et al. Recombinant human granulocyte-macrophage colony-stimulating factor after high-dose chemotherapy and autologous bone marrow transplantation with unpurged and purged marrow in non-Hodgkin's lymphoma: a double-blind placebo-controlled trial. Blood 1992; 80:1149.
- Gulati SC, Bennett CL. Granulocyte-macrophage colony-stimulating factor (GM-CSF) as adjunct therapy in relapsed Hodgkin disease. Ann Intern Med 1992; 116:177.
- Nemunaitis J, Rabinowe SN, Singer JW, et al. Recombinant granulocyte-macrophage colony-stimulating factor after autologous bone marrow transplantation for lymphoid cancer. N Engl J Med 1991; 324:1773.
- Jang G, Ko OB, Kim S, et al. Prospective randomized comparative observation of single- versus split-dose lenograstim to enhance engraftment after autologous stem cell transplantation in patients with multiple myeloma or non-Hodgkin's lymphoma. Transfusion 2008; 48:640.
- Gerds A, Fox-Geiman M, Dawravoo K, et al. Randomized phase III trial of pegfilgrastim versus filgrastim after autologus peripheral blood stem cell transplantation. Biol Blood Marrow Transplant 2010; 16:678.
- Rifkin R, Spitzer G, Orloff G, et al. Pegfilgrastim appears equivalent to daily dosing of filgrastim to treat neutropenia after autologous peripheral blood stem cell transplantation in patients with non-Hodgkin lymphoma. Clin Lymphoma Myeloma Leuk 2010; 10:186.
- Castagna L, Bramanti S, Levis A, et al. Pegfilgrastim versus filgrastim after high-dose chemotherapy and autologous peripheral blood stem cell support. Ann Oncol 2010; 21:1482.
- Sheridan WP, Begley CG, Juttner CA, et al. Effect of peripheral-blood progenitor cells mobilised by filgrastim (G-CSF) on platelet recovery after high-dose chemotherapy. Lancet 1992; 339:640.
- Nademanee A, Sniecinski I, Schmidt GM, et al. High-dose therapy followed by autologous peripheral-blood stem-cell transplantation for patients with Hodgkin's disease and non-Hodgkin's lymphoma using unprimed and granulocyte colony-stimulating factor-mobilized peripheral-blood stem cells. J Clin Oncol 1994; 12:2176.
- Smith TJ, Hillner BE, Schmitz N, et al. Economic analysis of a randomized clinical trial to compare filgrastim-mobilized peripheral-blood progenitor-cell transplantation and autologous bone marrow transplantation in patients with Hodgkin's and non-Hodgkin's lymphoma. J Clin Oncol 1997; 15:5.
- Spitzer G, Adkins DR, Spencer V, et al. Randomized study of growth factors post-peripheral-blood stem-cell transplant: neutrophil recovery is improved with modest clinical benefit. J Clin Oncol 1994; 12:661.
- Klumpp TR, Mangan KF, Goldberg SL, et al. Granulocyte colony-stimulating factor accelerates neutrophil engraftment following peripheral-blood stem-cell transplantation: a prospective, randomized trial. J Clin Oncol 1995; 13:1323.
- Demirer T, Ayli M, Dagli M, et al. Influence of post-transplant recombinant human granulocyte colony-stimulating factor administration on peritransplant morbidity in patients undergoing autologous stem cell transplantation. Br J Haematol 2002; 118:1104.
- Thompson JM, Carlton P, Akard LP, et al. Starting granulocyte-colony-stimulating factor (filgrastim) early after autologous peripheral blood progenitor cell transplantation leads to faster engraftment without increased resource utilization. Transfusion 2009; 49:548.
- Bensinger WI, Weaver CH, Appelbaum FR, et al. Transplantation of allogeneic peripheral blood stem cells mobilized by recombinant human granulocyte colony-stimulating factor. Blood 1995; 85:1655.
- Körbling M, Przepiorka D, Huh YO, et al. Allogeneic blood stem cell transplantation for refractory leukemia and lymphoma: potential advantage of blood over marrow allografts. Blood 1995; 85:1659.
- Schmitz N, Bacigalupo A, Labopin M, et al. Transplantation of peripheral blood progenitor cells from HLA-identical sibling donors. European Group for Blood and Marrow Transplantation (EBMT). Br J Haematol 1996; 95:715.
- Nemunaitis J, Rosenfeld CS, Ash R, et al. Phase III randomized, double-blind placebo-controlled trial of rhGM-CSF following allogeneic bone marrow transplantation. Bone Marrow Transplant 1995; 15:949.
- Bishop MR, Tarantolo SR, Geller RB, et al. A randomized, double-blind trial of filgrastim (granulocyte colony-stimulating factor) versus placebo following allogeneic blood stem cell transplantation. Blood 2000; 96:80.
- Przepiorka D, Smith TL, Folloder J, et al. Controlled trial of filgrastim for acceleration of neutrophil recovery after allogeneic blood stem cell transplantation from human leukocyte antigen-matched related donors. Blood 2001; 97:3405.
- Dallorso S, Rondelli R, Messina C, et al. Clinical benefits of granulocyte colony-stimulating factor therapy after hematopoietic stem cell transplant in children: results of a prospective randomized trial. Haematologica 2002; 87:1274.
- Ho VT, Mirza NQ, Junco Dd Dd, et al. The effect of hematopoietic growth factors on the risk of graft-vs-host disease after allogeneic hematopoietic stem cell transplantation: a meta-analysis. Bone Marrow Transplant 2003; 32:771.
- Khoury HJ, Loberiza FR Jr, Ringdén O, et al. Impact of posttransplantation G-CSF on outcomes of allogeneic hematopoietic stem cell transplantation. Blood 2006; 107:1712.
- Beguin Y, Clemons GK, Oris R, Fillet G. Circulating erythropoietin levels after bone marrow transplantation: inappropriate response to anemia in allogeneic transplants. Blood 1991; 77:868.
- Link H, Brune T, Hübner G, et al. Effect of recombinant human erythropoietin after allogenic bone marrow transplantation. Ann Hematol 1993; 67:169.
- Steegmann JL, López J, Otero MJ, et al. Erythropoietin treatment in allogeneic BMT accelerates erythroid reconstitution: results of a prospective controlled randomized trial. Bone Marrow Transplant 1992; 10:541.
- Klaesson S, Ringdén O, Ljungman P, et al. Reduced blood transfusions requirements after allogeneic bone marrow transplantation: results of a randomised, double-blind study with high-dose erythropoietin. Bone Marrow Transplant 1994; 13:397.
- Link H, Boogaerts MA, Fauser AA, et al. A controlled trial of recombinant human erythropoietin after bone marrow transplantation. Blood 1994; 84:3327.
- Biggs JC, Atkinson KA, Booker V, et al. Prospective randomised double-blind trial of the in vivo use of recombinant human erythropoietin in bone marrow transplantation from HLA-identical sibling donors. The Australian Bone Marrow Transplant Study Group. Bone Marrow Transplant 1995; 15:129.
- Jaspers A, Baron F, Willems E, et al. Erythropoietin therapy after allogeneic hematopoietic cell transplantation: a prospective, randomized trial. Blood 2014; 124:33.
- Chao NJ, Schriber JR, Long GD, et al. A randomized study of erythropoietin and granulocyte colony-stimulating factor (G-CSF) versus placebo and G-CSF for patients with Hodgkin's and non-Hodgkin's lymphoma undergoing autologous bone marrow transplantation. Blood 1994; 83:2823.
- Vannucchi AM, Bosi A, Ieri A, et al. Combination therapy with G-CSF and erythropoietin after autologous bone marrow transplantation for lymphoid malignancies: a randomized trial. Bone Marrow Transplant 1996; 17:527.
- Beguin Y, Maertens J, De Prijck B, et al. Darbepoetin-alfa and intravenous iron administration after autologous hematopoietic stem cell transplantation: a prospective multicenter randomized trial. Am J Hematol 2013; 88:990.
- Clark JR, Scott SD, Jack AL, et al. Monitoring of chimerism following allogeneic haematopoietic stem cell transplantation (HSCT): technical recommendations for the use of short tandem repeat (STR) based techniques, on behalf of the United Kingdom National External Quality Assessment Service for Leucocyte Immunophenotyping Chimerism Working Group. Br J Haematol 2015; 168:26.
- BLOOD PRODUCT SUPPORT
- Red blood cell transfusion
- Platelet transfusion
- Granulocyte transfusions
- GROWTH FACTOR SUPPORT
- G-CSF and GM-CSF
- - Autologous HCT
- Autologous PBPC transplantation
- - Allogeneic HCT
- Graft-versus-host disease
- - Allogeneic transplantation
- - Autologous transplantation