Hematopoietic support after hematopoietic cell transplantation

INTRODUCTION — Autologous and allogeneic hematopoietic cell transplantation (HCT) are associated with neutropenia, anemia, and thrombocytopenia in the peri-transplant period. The degree and duration of myelosuppression vary with the type of transplantation (ie, autologous versus allogeneic), preparative regimen, graft source (ie, bone marrow, peripheral blood, umbilical cord blood), and other factors. Blood product transfusions and hematopoietic growth factors are important aspects of care for the individual undergoing HCT.

Hematopoietic support for the patient who undergoes autologous or allogeneic HCT is discussed in this topic.

Early complications, including hematologic effects of HCT, are discussed separately. (See "Early complications of hematopoietic cell transplantation".)

PRIOR TO TRANSPLANTATION — Blood product support is usually required before, during, and following hematopoietic cell transplantation (HCT) [1].

Consultation with transfusion service — The blood transfusion service should be informed of the planned transplant to prepare for special blood component needs, such as leukocyte-reduced, cytomegalovirus (CMV)-seronegative, and/or gamma-irradiated blood components. Practices applied before transplantation continue throughout the course of transplantation and beyond. (See "Practical aspects of red blood cell transfusion in adults: Storage, processing, modifications, and infusion".)

Testing of recipient and graft donor — The transplant recipient and graft donor (if planning for an allogeneic HCT) require the following testing:

●HLA-typing – Patients should be typed for human leukocyte antigen (HLA) status to identify a compatible allogeneic graft and to select HLA-compatible blood products (eg, platelets). (See "Refractoriness to platelet transfusion".)

The role of HLA compatibility testing for allogeneic donor selection is discussed separately. (See "Donor selection for hematopoietic cell transplantation".)

●CMV status – CMV testing should be performed for the recipient and potential allogeneic blood and graft donors. (See "Platelet transfusion: Indications, ordering, and associated risks", section on 'Leukemia, chemotherapy, and HSCT'.)

Prevention of transfusion-associated CMV transmission is important for successful transplantation, as primary CMV infections increase morbidity and mortality in transplant recipients [2].

TRANSFUSION SUPPORT — Virtually all patients undergoing transplantation require blood product support until the transplanted cells engraft sufficiently to support adequate hematopoiesis. Intensive transfusion support is often needed, especially in the face of active bleeding, infection, and other HCT-associated complications [3].

Transfusion services in hospitals where HCT is performed are required to have guidelines for transfusion support during the peri-transplantation period (ie, from conditioning therapy to recovery of hematopoiesis). Indications for transfusions for patients undergoing HCT resemble those for other cytopenic patients.

Autologous HCT can be performed safely in patients who decline transfusion of blood products [4]. Management of patients who decline blood transfusion for religious or other reasons is discussed separately. (See "Approach to the patient who declines blood transfusion".)

Duration of transfusion support — The period of transfusion-requiring cytopenias varies with the type of transplant (ie, autologous versus allogeneic), preparative regimen, graft source (ie, bone marrow, peripheral blood, umbilical cord blood), medications, and transplant-associated complications.

Recovery of hematopoiesis generally requires ≥14 to 21 days with bone marrow grafts, but it is faster with peripheral blood stem/progenitor cell (PBSPC) grafts, usually requiring 10 to 14 days. Compared with myeloablative conditioning (MAC), transfusion needs are generally lower in patients undergoing non-myeloablative (NMA) regimens. In a retrospective analysis, compared with MAC, fewer patients undergoing NMA transplantation required transfusions of platelets (23 versus 100 percent) and red blood cells (RBC) (63 versus 96 percent) [5].

Leukoreduction — For all patients undergoing HCT, only leukoreduced blood products should be transfused, to reduce febrile nonhemolytic transfusion reactions (FNHTRs), alloimmunization, and transmission of infections. Use of leukoreduced blood products is standard practice for all transplant recipients.

Leukoreduction refers to use of a leukocyte reduction filter to selectively remove leukocytes. This generally reduces the leukocyte count by three to four logs (99.9 to 99.99 percent) and achieves a final leukocyte count <5 million/unit (<5 x 10⁶; the US Food and Drug Administration [FDA]-required limit) and generally <1 million/unit. Leukoreduction is generally performed pre-storage, but in some cases, it can be done at the time of transfusion ("bedside").

Leukoreduction decreases risks for FNHTRs, human leukocyte antigen (HLA) alloimmunization, and transmission of cytomegalovirus (CMV; which resides in WBCs) [6]. However, leukocyte filters do not completely prevent HLA alloimmunization in all transfusion recipients, because some leukocytes and/or membrane fragments can pass through standard leukocyte reduction filters. As an example, up to 20 percent of patients in the Trial to Reduce Alloimmunization to Platelets study developed HLA antibodies, despite stringent leukocyte filtration [7]. (See "Practical aspects of red blood cell transfusion in adults: Storage, processing, modifications, and infusion", section on 'Pre-storage leukoreduction'.)

Cytomegalovirus (CMV) — The risk of post-transplant CMV infection and CMV disease is influenced by donor and recipient CMV serostatus, which must be determined prior to transplant. (See 'Testing of recipient and graft donor' above.)

CMV infection is a major source of morbidity and mortality in transplant recipients, and prevention of CMV disease is important for successful HCT [2]. Although some autologous HCT recipients reactivate latent CMV, the incidence of CMV disease in these patients is low. For allogeneic HCT, the lowest risk of post-transplant CMV is with CMV-seronegative recipients given grafts from CMV-seronegative donors. In CMV-seropositive allogeneic HCT recipients, the greatest risk for the development of CMV disease after transplant is reactivation of latent infection (rather than transfused seropositive blood). (See "Prevention of viral infections in hematopoietic cell transplant recipients".)

CMV seronegative and CMV seropositive patients differ in their blood product needs, as follows.

CMV infection in transplanted patients is discussed separately. (See "Prevention of viral infections in hematopoietic cell transplant recipients".)

CMV seronegative recipients — For CMV seronegative transplant recipients, we suggest using only seronegative blood products and graft, based on prevention of CMV infection and avoidance of adverse effects (AEs) of preventive antiviral treatments. Use of seronegative blood products in this setting is standard practice because of the severe consequences of CMV infection in this setting.

We generally continue use of CMV-seronegative products for these patients until immunosuppression is withdrawn. Although leukoreduction can reduce CMV transmission, it is not an adequate substitute for CMV-seronegative blood products. However, if an urgent transfusion is needed and CMV-seronegative blood components are not adequate to meet the patient's needs, leukoreduction can reduce the risk that CMV will infect CMV-seronegative recipients [8].

The incidence of CMV infections is significantly decreased in transplant recipients who are CMV-seronegative and exposed only to CMV-seronegative blood products (including a seronegative graft). Avoiding the need for antiviral treatment prevents adverse effects, which can further suppress hematopoiesis or be nephrotoxic in the transplanted patient [2].

CMV positive recipients — For CMV seropositive transplant recipients, transfusion with either seronegative or seropositive blood products is acceptable.

In CMV seropositive patients, the most common cause of CMV disease is reactivation of latent CMV (from prior exposure); use of seronegative blood products appears to have little impact on CMV reactivation. There is no direct evidence that re-infection of CMV seropositive patients can occur with a second strain of CMV from a CMV-positive graft or transfused blood product.

Most transplant centers routinely administer pre-emptive antiviral treatment to seropositive recipients in whom immunocompetence is delayed. Even with pre-emptive antiviral treatment, CMV reactivation is higher in seropositive recipients who receive haploidentical; T cell–depleted; unrelated, HLA-mismatched grafts; or non-genotypically typed HLA-matched sibling grafts. (See "Prevention of viral infections in hematopoietic cell transplant recipients", section on 'CMV prevention'.)

Gamma irradiation — For all recipients of autologous or allogeneic grafts who require transfusion, we suggest using only gamma-irradiated blood products in the peri-transplantation and post-transplantation periods, based on reduced risk of transfusion-associated graft-versus-host disease (TA-GVHD).

Irradiation of blood products is standard practice in the peri-transplantation and post-transplantation periods for all patients undergoing transplantation [9]. Use of irradiated blood products should be instituted as soon as a patient is identified as a potential transplant candidate. The duration of use of irradiated products varies among centers [10]. Some centers continue to use irradiated products indefinitely, while others continue this practice until hematological reconstitution, for a specified period (eg, six months), or until immunosuppressive medications are no longer required.

Donor lymphocytes can be detected in the circulation of immunoincompetent individuals for months to years after the transfusion of freshly collected RBC or platelet components (so-called microchimerism); the lymphocytes can engraft in a susceptible immunosuppressed host and cause TA-GVHD [11]. Gamma irradiation prevents TA-GVHD by inducing DNA crosslinks, thereby preventing proliferation of donor lymphocytes. Irradiation is the only reliable method for preventing TA-GVHD, as leukoreduction filtration methods and chemical exposures (eg, psoralens) do not completely prevent TA-GVHD [12].

Clinical symptoms of TA-GVHD occur between 4 and 30 days after transfusion and may include fever, maculopapular rash, bloody diarrhea, and/or pancytopenia. Although TA-GVHD is uncommon, the mortality rate is high. TA-GVHD is discussed in greater detail separately. (See "Transfusion-associated graft-versus-host disease".)

Iron overload — Iron overload is commonly seen in 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 [13-15].

Recognition and management of iron overload is discussed separately. (See "Approach to the patient with suspected iron overload".)

BLOOD PRODUCTS — There are no specific guidelines for transfusion thresholds in patients undergoing HCT, but they resemble those for other cytopenic patients. (See "Indications and hemoglobin thresholds for RBC transfusion in adults" and "Platelet transfusion: Indications, ordering, and associated risks".)

Red blood cells — There is no consensus hemoglobin (Hb) threshold that should trigger transfusion of red blood cells (RBC). Practices vary, but many centers use Hb 7 to 8 g/dL to trigger RBC transfusion. Such a restrictive transfusion strategy is safe, effective, and may reduce transfusion-related adverse events. (See "Practical aspects of red blood cell transfusion in adults: Storage, processing, modifications, and infusion", section on 'Whole blood'.)

The transfusion threshold may be influenced by the patient's clinical condition, days since transplantation, and evidence of engraftment of other cell types, including reticulocytes. Patients with GVHD and those treated with immunosuppressive drugs, such as cyclosporine or tacrolimus, may have continued blood product requirements due to bleeding and/or microangiopathic hemolysis.

The rationale for use of leukoreduced, gamma-irradiated blood products with strict attention to CMV status of the donor and recipient is addressed above. (See 'Transfusion support' above.)

Typically, type O blood is utilized if there is a major ABO mismatch between donor and recipient until engraftment of donor RBCs is confirmed. Cases of delayed hemolysis and/or pure red cell aplasia have been described in patients with pre-existing alloantibodies against Rh or ABO antigens, despite the presence of 100 percent donor chimerism of the circulating lymphocytes, as discussed separately. (See "Donor selection for hematopoietic cell transplantation", section on 'ABO and Rh status'.)

In a multicenter trial that included 300 patients undergoing autologous or allogeneic HCT for a hematologic malignancy, there was no difference in outcomes between patients who were randomly assigned to a restrictive transfusion threshold (Hb 7g/dL) versus a liberal transfusion strategy (Hb 9 g/dL) [16]. Compared with the liberal threshold, patients treated with a restrictive strategy received fewer transfusions (2.7 versus 5.0, respectively), but there was no difference in transplant outcomes or health-related quality of life, including transplant-related mortality at day 100, length of hospital stay, intensive care unit admissions, hospital re-admissions, acute GVHD, grade ≥3 infections, or bleeding.

Platelets — Patients who are severely thrombocytopenic, with or without bleeding, require platelet transfusions. We generally transfuse prophylactically for platelet counts <10,000/microL and transfuse at higher values if clinical bleeding is present (table 1).

This approach is supported by a meta-analysis of randomized trials of prophylactic platelet transfusions versus no prophylaxis [17] and is consistent with the 2017 American Society of Clinical Oncology (ASCO) platelet transfusion guidelines (table 1) [18] and the 2015 AABB (formerly Association for the Advancement of Blood & Biotherapies) practice guidelines [19], as discussed separately. (See "Platelet transfusion: Indications, ordering, and associated risks" and "Platelet transfusion: Indications, ordering, and associated risks", section on 'Prevention of spontaneous bleeding'.)

Multicenter randomized trials that addressed platelet transfusions in the setting of HCT include:

●In a randomized trial, 400 patients undergoing autologous HCT for a hematologic malignancy or with acute leukemia were randomly assigned to receive platelet transfusions when morning platelet counts were ≤10,000/microL versus only for active bleeding [20]. Patients transfused only for active bleeding received fewer platelet transfusions in the first 14 days (1.6 versus 2.4 transfusions per patient). Among patients undergoing HCT, there were more bleeding episodes among those transfused only for active bleeding, but most episodes were minor.

●In the randomized TOPPS trial (Trial of Prophylactic Platelets), 600 patients with hematologic malignancies receiving chemotherapy, autologous, or allogeneic HCT were assigned to receive platelet transfusion for a platelet count ≤10,000/microL versus only for active bleeding [21-23]. Compared with prophylactic transfusions, patients transfused only for active bleeding received fewer platelet transfusions, but had a higher incidence of major bleeding (50 versus 43 percent) and a shorter time to first bleed (1.2 versus 1.7 days) [24]. There were no differences in duration of hospitalization and no deaths due to bleeding. In a pre-defined subgroup analysis, patients undergoing autologous HCT had similar rates of major bleeding whether they were transfused for a platelet count ≤10,000/microL or only for active bleeding (45 and 47 percent).

Studies that compared threshold for platelet transfusion reported that, compared with patients prophylactically transfused for platelets of 20,000/microL or 30,000/microL, those transfused at 10,000/microL received increased platelet transfusions, but had only a small adverse effect [25,26] or no effect [27] on bleeding. (See "Platelet transfusion: Indications, ordering, and associated risks", section on 'Leukemia, chemotherapy, and HSCT'.)

Granulocytes — Granulocyte transfusions are generally not used because of the lack of efficacy in clinical trials and the difficulty of obtaining sufficient cells due to the short half-life of neutrophils.

There are few, if any, clinical indications for granulocyte transfusions outside of a clinical trial setting. (See "Granulocyte transfusions".)

GROWTH FACTOR SUPPORT — Hematopoietic growth factors (colony-stimulating factors [CSFs]) that have been evaluated in the transplant setting include granulocyte (G)-CSF, granulocyte-macrophage (GM)-CSF, erythropoietin (EPO), and thrombopoietic factors. (See "Introduction to recombinant hematopoietic growth factors".)

Use of hematopoietic growth factors for mobilization of stem cells in donors of peripheral blood stem/progenitor cell (PBSPC) grafts, as discussed separately. (See "Evaluation of the hematopoietic cell transplantation donor", section on 'Peripheral blood progenitor cell (PBPC) collection'.)

G-CSF/GM-CSF — Use of G-CSF and GM-CSF varies according to the type of transplant.

Autologous HCT — For patients undergoing autologous HCT, we suggest administration of G-CSF or GM-CSF to shorten the duration of severe neutropenia, as demonstrated by a meta-analysis and randomized trials.

There is no preferred agent, regimen, or route of administration. Treatment is usually begun one to five days after transplantation and continued until absolute neutrophil count (ANC) ≥10,000/microL, but a lower ANC threshold is acceptable. We consider any of the following regimens acceptable:

●G-CSF – Single dose of pegfilgrastim (6 mg) or daily filgrastim (5 mcg/kg/d), intravenously or subcutaneously

●GM-CSF – Daily intravenous or subcutaneous GM-CSF (250 microg/m²)

Treatment with G-CSF or GM-CSF hastened neutrophil recovery in a meta-analysis and in multiple phase 3 trials, but only a subset of studies reported improvements in infection-associated outcomes (eg, number or severity of infections, days with fever, duration of antibiotic use) or shortened hospitalization, and none reported a difference in rates of survival or relapse. There are no reports of excess toxicity with these agents in patients undergoing autologous HCT. Informative studies include:

●Meta-analysis – A 2006 meta-analysis included 34 trials of HCT that randomly assigned patients to either G-CSF or GM-CSF versus placebo/no therapy; 25 of the trials included patients undergoing autologous HCT [28]. Treatment significantly accelerated neutrophil recovery to 500/microL (weighted mean difference [WMD] 4.0 days), reduced days of parenteral antibiotics (WMD 1.2 days), and hastened hospital discharge (WMD -2.9 days, [-3.8 to -2.1 days]); there was a trend toward fewer documented infections (relative risk [RR] 0.87 [95% CI 0.76-1.00]) with CSF treatment, but there was no impact on survival or treatment-related mortality (TRM). However, when analyzing the four trials that included only autologous HCT and reported survival data, treatment was associated with improved overall survival (OS; RR 0.89 [95% CI 0.79-0.99]).

●Randomized trials – Multiple randomized, placebo-controlled (or no treatment-controlled) trials in autologous HCT reported that either G-CSF [29-32] or GM-CSF [33-37] hastened resolution of neutropenia, but only a subset reported improvements in various infection-related outcomes, while none reported improved survival.

●Choice of regimen – No randomized trials have directly compared G-CSF versus GM-CSF after autologous HCT. Three randomized trials that compared pegfilgrastim versus filgrastim reported no differences in neutrophil recovery, infectious outcomes, or survival [38-40]. Another phase 3 trial reported no difference when lenograstim (G-CSF from prepared with Chinese hamster ovary cells) was administered once daily versus split-dose administration (twice-daily) [41]. A retrospective study reported that beginning G-CSF on the day of stem cell infusion was associated with resolution of neutropenia one day earlier than treatment beginning on day 5 [32], but another study reported no difference between these approaches [31].

Allogeneic HCT — For selected patients undergoing allogeneic HCT, we suggest administration of G-CSF or GM-CSF; this includes patients who undergo non-myeloablative conditioning, receive an umbilical cord graft, are treated with post-transplant cyclophosphamide, or experience slow hematologic reconstitution. For others, we generally do not incorporate a CSF, given controversial data regarding adverse effects.

Our approach is consistent with the 2015 American Society of Clinical Oncology guidelines on cytokine use [18].

Informative studies of CSFs after allogeneic HCT include:

●Meta-analysis – The 2006 meta-analysis (described above) reported that in five randomized placebo-controlled or no treatment-controlled trials of patients undergoing allogeneic HCT, G-CSF or GM-CSF was associated with faster neutrophil recovery and fewer documented infections, but there was no effect on OS, TRM, grade 2-4 acute GVHD (aGVHD), days of parenteral antibiotics, or days to hospital discharge [28].

●Randomized trials – Individual randomized, controlled trials in patients undergoing allogeneic HCT reported faster neutrophil engraftment, but no effect on OS or GVHD [42-44]. A trial in children reported faster neutrophil recovery, but no increase in GVHD in recipients of allogeneic bone marrow grafts in association with G-CSF [45].

●Other studies:

•A large retrospective analysis of patients transplanted with HLA-matched sibling donor grafts for acute leukemia reported that, compared with no G-CSF treatment controls, recipients of bone marrow grafts treated with G-CSF had decreased survival and increased adverse events; no such effect was reported for recipients of PBSPC grafts [46]. For recipients of bone marrow grafts, patients treated with G-CSF had inferior OS (relative risk [RR] 0.59 [95% CI 0.46-0.75]), inferior leukemia-free survival (RR 0.64 [95% CI 0.51-0.81]), increased TRM (27 versus 17 percent; RR, 1.73 [95% CI 1.3-12.32]), increased grade 2-4 aGVHD (50 percent versus 39 percent; RR 1.33 [95% CI 1.08-1.64]), and increased chronic GVHD (cGVHD; 37 versus 28 percent; RR 1.29 [95% CI 1.02-1.61]). No such inferior effects of G-CSF were seen in patients receiving G-CSF with PBSPC grafts.

•In another retrospective study of allogeneic HCT, comparison of 260 patients given G-CSF versus 205 controls (no G-CSF) reported no difference in OS, non-relapse mortality, or relapse, but increased GVHD [47]. G-CSF was associated with increased grade 2-4 aGVHD (29 versus 19 percent; hazard ratio [HR] 1.52 [95% CI 1.06-2.32]) and cGVHD (54 versus 43 percent; HR 1.51 [95% CI 1.14-2.00]). G-CSF was associated with increased aGVHD in recipients of PBSPC grafts (but not with bone marrow grafts) and increased cGVHD in recipients of bone marrow grafts (but not with PBSPC grafts).

•A single-institution study of 155 patients that included 66 (44 percent) who received G-CSF reported that patients receiving G-CSF had more grade 2-4 aGVHD (34 versus 9 percent), which was independent of other risk factors for GVHD [48]. There was no difference in OS, TRM, relapse, or cGVHD between the groups. 

Erythropoietin (EPO) — For patients undergoing either autologous or allogeneic HCT, we suggest not routinely administering erythropoietin (EPO), based on little or no effect on red blood cell (RBC) transfusion requirements. For transplant patients, EPO is generally reserved for those with prolonged anemia (eg, RBC transfusion requirements after day 28) and for those who develop recurrent anemia after recovery of hemoglobin (Hb) level.

●Autologous HCT – Three randomized clinical trials reported no benefit for EPO after autologous transplantation in patients who were also treated with G-CSF; none of the trials found a significant reduction in RBC transfusion requirements [49-52].

●Allogeneic HCT – A placebo-controlled trial of 131 patients undergoing allogeneic HCT reported modest reductions in transfusions for patients who received EPO [53]. There were three cohorts of patients who were randomly assigned to placebo versus EPO (500 units/kg weekly): myeloablative HCT with placebo or EPO starting on day 28; nonmyeloablative HCT with placebo versus EPO starting on day 28; or nonmyeloablative HCT with placebo versus EPO starting on day 0 [53]. EPO was associated with fewer patients requiring transfusion (42 versus 77 percent) and fewer RBC units transfused per patient (4.1 versus 6.9 units). Patients who received EPO were also more likely to have attained Hb ≥13 g/dL by day 126 (63 versus 8 percent, median 90 days versus not reached). Among those undergoing nonmyeloablative HCT, there was no additional benefit to starting EPO at day 0 compared with starting on day 28.

A phase 3 placebo-controlled trial of 215 patients undergoing allogeneic HCT recipients reported that compared with placebo, EPO (150 units/kg per day as a continuous infusion) achieved shorter median time to transfusion independence (27 versus 19 days), but the number of transfusions was similar in the two groups [49].

Among 91 patients randomly assigned to placebo versus EPO (300 units/kg three times weekly) after allogeneic transplantation, there was no difference in transfusion requirements, although EPO therapy was associated with increases in the reticulocyte count, Hb concentration, and bone marrow erythropoiesis on day 14 [54].

Post-transplant anemia is often multifactorial and may be affected by medications (eg, ganciclovir, cyclosporine), GVHD, and other transplant-associated conditions.

Thrombopoietic growth factors — There is no current role for thrombopoietic growth factors after either autologous or allogeneic HCT.

There has been little evaluation of thrombopoietins (eg, romiplostim, eltrombopag) in this setting. Although generally well-tolerated, there is limited evidence that these agents accelerate platelet recovery, reduce bleeding, or lessen platelet transfusion requirements after transplantation [55-57].

Thrombopoietic agents and their clinical applications are discussed separately. (See "Clinical applications of thrombopoietic growth factors".)

SUMMARY AND RECOMMENDATIONS

●Description – Virtually all patients undergoing autologous or allogeneic hematopoietic cell transplantation (HCT) require blood product support in the form of red blood cell (RBC) and/or platelet transfusions until the transplanted marrow cells engraft sufficiently to support hematopoiesis.

●Prior to transplantation – Important actions before transplantation include:

•The blood transfusion service should be informed of the planned transplant to prepare for special blood component needs. (See 'Consultation with transfusion service' above.)

•Human leukocyte antigen (HLA) status and CMV testing should be performed for the recipient and potential allogeneic donors.

●Transfusion support – The period of transfusion-requiring cytopenias varies with the type of transplant (ie, autologous versus allogeneic), preparative regimen, graft source (ie, bone marrow, peripheral blood, umbilical cord blood), medications, and transplant-associated complications. With bone marrow grafts, recovery of hematopoiesis generally requires ≥14 to 21 days, but it is faster with peripheral blood stem/progenitor cell (PBSPC) grafts (eg, 10 to 14 days).

●Leukoreduction – For all patients undergoing HCT who require transfusions, we suggest use of only leukoreduced blood products, to reduce risks for febrile nonhemolytic transfusion reactions, alloimmunization, and transmission of infections (Grade 2C). (See 'Leukoreduction' above.)

●Cytomegalovirus (CMV) – The risk of post-transplant CMV infection and/or disease varies with CMV serostatus of the transplant recipient.

•CMV seronegative recipients – For CMV seronegative transplant recipients, we suggest transfusion with only seronegative blood products to prevent CMV infection and avoid adverse effects of preventive antiviral treatments. (Grade 2C) (See 'CMV seronegative recipients' above.)

•CMV seropositive recipients – For CMV seropositive transplant recipients, transfusion with either seronegative or seropositive blood products is acceptable. (See 'CMV positive recipients' above.)

●Gamma irradiation – For all recipients of autologous or allogeneic grafts, we suggest using only gamma-irradiated blood products in the peri- and post-transplantation period, to reduce risk of transfusion-associated graft-versus-host disease (TA-GVHD). (Grade 2C) (See 'Gamma irradiation' above.)

●Transfusion thresholds – Transfusion thresholds for RBCs and platelets are similar to those for other cytopenic patients. (See "Indications and hemoglobin thresholds for RBC transfusion in adults" and "Platelet transfusion: Indications, ordering, and associated risks".)

●Growth factor support – Use of hematopoietic growth factors (colony stimulating factors [CSFs]) varies with the type of transplant:

•G-CSF and GM-CSF:

-Autologous – For patients undergoing autologous HCT, we suggest G-CSF or GM-CSF to shorten the duration of severe neutropenia. (Grade 1B) (See 'Autologous HCT' above.)

-Allogeneic – For select patients undergoing allogeneic HCT, we suggest G-CSF or GM-CSF; this includes patients who undergo non-myeloablative conditioning, receive an umbilical cord graft, are treated with post-transplant cyclophosphamide, or experience slow hematologic reconstitution (Grade 2C). For others, we generally do not incorporate a CSF, given controversial data regarding adverse effects. (See 'Allogeneic HCT' above.)

•Erythropoietin (EPO) – For patients undergoing either autologous or allogeneic HCT, we suggest not routinely administering erythropoietin (EPO) (Grade 2C). (See 'Erythropoietin (EPO)' above.)

•Thrombopoietic growth factors – There is no demonstrated role for these factors in the post-transplant period. (See 'Thrombopoietic growth factors' above.)