Ethical Challenges in Hematopoietic Cell Transplantation for Sickle Cell Disease

Hematopoietic cell transplantation (HCT) using an HLA-identical sibling donor offers a very high likelihood of cure with good outcomes for patients with sickle cell disease (SCD), and alternative donor HCT for SCD is an area of active clinical research. Thus, HCT is a potential option for a growing number of patients with SCD. This expanded use of HCT has raised several ethical questions. Who is eligible for HCT, in terms of both disease severity and psychosocial factors? Should affected children with matched sibling donors undergo HCT only when they have declared themselves as having significant symptomatology? Regarding donors, special ethical challenges include the use of preimplantation genetic diagnosis to conceive an HLA-identical sibling. In this review, we critically analyze various ethical challenges related to HCT for SCD, and offer recommendations to guide clinical care.     

Acceleration of Immune Reconstitution after Bone Marrow Transplantation in Mice by Bone Marrow Stromal Cell Line Transfected with IL-6 Gene

After bone marrow transplantation, dysfunction of immunesystem is a critical problem to be resolved in clinical treat ment. Efficient bone marrow transplantation needs com pleted immune reconstitution, which is associated to manyfactors. Among them, Chemo/radiotherapy after and/orbefore BMT can cause great damage to hematopoietic mi croenvironment, which decrease the ability of proliferationand differentiation of stem cell[1]. To observe the effectof bone marrow stromal cell on the imm…     

IL-17 Gene Ablation Does Not Impact Treg-Mediated Suppression of Graft-Versus-Host Disease after Bone Marrow Transplantation

Regulatory T cell (Treg) immunotherapy is a promising strategy for the treatment of graft rejection responses and autoimmune disorders. Our and other laboratories have shown that the transfer of highly purified CD4⁺CD25⁺Foxp3⁺ natural Treg can prevent lethal graft-versus-host disease (GVHD) after allogeneic hematopoietic cell transplantation across both major and minor histocompatibility barriers. However, recent evidence suggests that the Treg suppressive phenotype can become unstable, a phenomenon that can culminate in Treg conversion into IL-17–producing cells. We hypothesized that the intense proinflammatory signals released during an ongoing alloreaction might redirect a fraction of the transferred Treg to the Th17 cell fate, thereby losing immunosuppressive potential. We therefore sought to evaluate the impact of Il17 gene ablation on Treg stability and immunosuppressive capacity in a major MHC mismatch model. We show that although Il17 gene ablation results in a mildly enhanced Treg immunosuppressive ability in vitro, such improvement is not observed when IL-17–deficient Treg are used for GVHD suppression in vivo. Similarly, when we selectively blocked IL-1 signaling in Treg, that was shown to be necessary for Th17 conversion, we did not detect any improvement on Treg_-mediated GVHD suppressive ability in vivo. Furthermore, upon ex vivo reisolation of transferred wild-type Treg, we detected little or no Treg_-mediated IL-17 production upon GVHD induction. Our results indicate that blocking Th17 conversion does not affect the GVHD suppressive ability of highly purified natural Treg in vivo, suggesting that IL-17 targeting is not a valuable strategy to improve Treg immunotherapy after hematopoietic cell transplantation.     

Dynamic of Bone Marrow Fibrosis Regression Predicts Survival after Allogeneic Stem Cell Transplantation for Myelofibrosis

We correlate regression of bone marrow fibrosis (BMF) on day 30 and 100 after dose- reduced allogeneic stem cell transplantation (allo-SCT) in 57 patients with primary or post–essential thrombocythemia/polycythemia vera myelofibrosis with graft function and survival. The distribution of International Prognostic Scoring System (IPSS) risk score categories was 1 patient with low risk, 5 patients with intermediate-1 risk, 18 patients with intermediate-2 risk, and 33 patients with high risk. Before allo-SCT, 41 patients (72%) were classified as XXX [myclofibrosis (MF)]-3 and 16 (28%) were classified as MF-2 according to the World Health Organization criteria. At postengraftment day +30 (±10 days), 21% of the patients had near-complete or complete regression of BMF (MF-0/-1), and on day +100 (±20 days), 54% were MF-0/-1. The 5-year overall survival rate at day +100 was 96% in patients with MF-0/-1 and 57% for those with MF-2/-3 (P = .04). There was no difference in BMF regression at day +100 between IPSS high-risk and low/intermediate-risk patients. Complete donor cell chimerism at day +100 was seen in 81% of patients with MF-0/-1 and in 31% of those with MF-2/-3. Patients with MF-2/-3 at day +100 were more likely to be transfusion-dependent for either RBCs (P = .014) or platelets (P = .018). Rapid BMF regression after reduced-intensity conditioning allo-SCT resulted in a favorable survival independent of IPSS risk score at transplantation.     

Association between an Impaired Bone Marrow Vascular Microenvironment and Prolonged Isolated Thrombocytopenia after Allogeneic Hematopoietic Stem Cell Transplantation

Prolonged isolated thrombocytopenia (PT) is a serious complication after allogeneic hematopoietic stem cell transplantation (allo-HSCT). However, it remains unclear whether abnormalities of the bone marrow (BM) microenvironment are involved in the pathogenesis of PT. This prospective, nested case-control study included 20 patients with PT, 40 matched patients with good graft function (GGF) after allo-HSCT, and 16 healthy donors (HDs). Cellular elements of the BM microenvironment, including BM endothelial cells (BMECs), perivascular cells, and endosteal cells, were analyzed via flow cytometry and via hematoxylin-eosin and immunohistochemical staining in situ. Moreover, stromal-derived factor 1 (SDF-1) and vascular endothelial growth factor (VEGF) were measured in the plasma of BM via an enzyme-linked immunosorbent assay. No significant differences in endosteal cells (15 per high-power field [hpf] versus 16 per hpf versus 20 per hpf, P > .05) were demonstrated among the patients with PT, GGF, and the HDs. The PT patients exhibited remarkable decreases in cellular elements of the vascular microenvironment, including BMECs (.01% versus .18% versus .20%, P < .0001) and perivascular cells (.01% versus .12% versus .13%, P < .0001), compared with the GGF allo-HSCT recipients and the HDs, respectively. Moreover, significantly lower levels of SDF-1 (3163 pg/mL versus 3928 pg/mL, P = .0002) and VEGF (56 pg/mL versus 123 pg/mL, P < .0001) were found in the BM plasma of the PT patients compared with the BM of the GGF patients. A multivariate analysis revealed that BMECs (odds ratio [OR] = 171.57, P = .002) and cytomegalovirus infection after HSCT (OR = 4.35, P = .009) were independent risk factors for PT. Our data suggested that an impaired BM vascular microenvironment and megakaryocyte-active factors may contribute to the occurrence of PT after HSCT.     

Comparable Long-Term Outcome of Unrelated Cord Blood Transplantation with Related Bone Marrow or Peripheral Blood Stem Cell Transplantation in Patients Aged 45 Years or Older with Hematologic Malignancies after Myeloablative Conditioning

We investigated whether bone marrow or peripheral blood stem cells from older sibling donors or cord blood from unrelated donors provided a better outcome in allogeneic hematopoietic stem cell transplantation for relatively older patients who were candidates for myeloablative conditioning. Clinical outcomes of 97 patients aged 45 years or older with hematologic malignancies who received unrelated cord blood transplantation (CBT) (n = 66) or bone marrow transplantation (BMT) or peripheral blood stem cell transplantation (PBSCT) from related donors (n = 31) were compared. The cumulative incidences of grades III to IV acute and extensive chronic graft-versus-host diseases were similar between both groups. Although transplant-related mortality was significantly lower after CBT compared with BMT/PBSCT from related donors (hazard ratio [HR], .29, P = .04), overall mortality (HR, .72, P = .47) and relapse (HR, 2.02, P = .23) were not significantly different after CBT and BMT/PBSCT from related donors. These data suggest that CBT could be as safe and effective as BMT/PBSCT from older related donors for relatively older patients when it is used as a primary unrelated stem cell source.     

Bone Marrow Graft-versus-Host Disease: Evaluation of Its Clinical Impact on Disrupted Hematopoiesis after Allogeneic Hematopoietic Stem Cell Transplantation

Idiopathic cytopenias are frequently observed in patients after allogeneic hematopoietic stem cell transplantation (allo-HSCT). We have previously reported the effect of graft-versus-host disease (GVHD) on bone marrow (BM) in murine models, indicating that the osteoblast injury mediated by donor T cells was associated with bone marrow suppression and delayed immune reconstitution. In this study, we prospectively evaluated the relevance of these findings in 51 patients. Patients with chronic GVHD manifested the loss of osteoblasts, contributing to cytopenic symptoms (P = .0427 compared with patients without cytopenic symptoms). The loss of osteoblasts was significantly associated with the extensive type of chronic GVHD (P = .012), and flow cytometric analyses revealed lower numbers of CD19⁺ B cells and a significantly increased CD4 to CD8 ratio (P = .0002) in these patients. Our data, for the first time to our knowledge, summarize the detailed analyses of the effect of GVHD on BM in the clinical allo-HSCT patients.     

Association of an Impaired Bone Marrow Microenvironment with Secondary Poor Graft Function after Allogeneic Hematopoietic Stem Cell Transplantation

Poor graft function (PGF) is a serious complication after allogeneic hematopoietic stem cell transplantation (allo-HSCT). Whether abnormalities of the bone marrow (BM) microenvironment are involved in the pathogenesis of PGF is unclear. In the present prospective nested case-control study, 19 patients with secondary PGF, 38 matched patients with good graft function (GGF) after allo-HSCT, and 15 healthy donors (HDs) were enrolled. The cellular elements of the BM microenvironment, including endosteal cells, perivascular cells, and vascular cells, were analyzed by flow cytometry as well as hematoxylin and eosin and immunohistochemical staining in situ. The median time to occurrence of secondary PGF was 90 days post-transplantation (range, 58 to 264 days). The patients with PGF showed markedly hypocellular marrow (10% versus 45% versus 45%; P < .0001) with scattered hematopoietic cells and significantly lower CD34⁺ cells (0.07% versus 0.26% versus 0.26%; P < .0001), endosteal cells (4 per high-power field [hpf] versus 16 per hpf versus 20 per hpf; P < .001), perivascular cells (0.008% versus 0.10% versus 0.12%; P < .0001), and endothelial progenitor cells (0.008% versus 0.16% versus 0.18%; P < .0001) compared with GGF allo-HSCT recipients and HDs, respectively. Multivariate analyses revealed that endothelial progenitor cells (odds ratio, 150.72; P = .001) and the underlying disease (odds ratio, 18.52; P = .007) were independent risk factors for secondary PGF. Our results suggest that the impaired BM microenvironment may contribute to the occurrence of secondary PGF post-HSCT.     

Bone Marrow Compared with Peripheral Blood Stem Cells for Haploidentical Transplantation with a Nonmyeloablative Conditioning Regimen and Post-transplantation Cyclophosphamide

Recently, the administration of high-dose cyclophosphamide (Cy) after T cell–replete haploidentical stem cell infusion has been reported to be feasible and effective. In the original study, bone marrow (BM) was used as the source of stem cells. Here, we retrospectively analyzed the use of BM versus peripheral blood stem cells (PBSCs) in a cohort of patients receiving haploidentical T cell–replete transplantation after a nonmyeloablative conditioning regimen with postinfusion Cy. In the PBSC versus BM groups, the incidence of acute graft-versus-host disease (GVHD) was 33% versus 25%, respectively, and the incidence of chronic GVHD was 13% versus 13%, respectively. The median time to achieve a safe and unsupported absolute neutrophil and platelet count was 20 versus 21 days and 27 versus 29 days, respectively. The incidence of engraftment was also similar in the 2 cohorts. The 1-year nonrelapse mortality rate was 12% versus 22%, respectively (P = .96). Finally, nonsignificant differences in survival were observed. In conclusion, the use of PBSCs instead of BM after T cell–replete haploidentical transplantation did not appear to be detrimental in terms of either GVHD or engraftment rate. PBSCs could be a valid alternative to BM after transplantation from a haploidentical donor using postinfusion Cy.     

HLA Haploidentical Stem Cell Transplant with Pretransplant Immunosuppression for Patients with Sickle Cell Disease

Allogeneic stem cell transplantation (HCT) is curative in patients with severe sickle cell disease (SCD), but a significant number of patients lack an HLA-identical sibling or matched unrelated donor. Mismatched related (haploidentical) HCT with post-transplant cyclophosphamide (PTCY) allows expansion of the donor pool but is complicated by high rates of graft failure. In this report we describe a favorable haploidentical HCT approach in a limited cohort of SCD patients with significant comorbidities. To reduce the risk of graft failure we administered the conditioning regimen of rabbit antithymocyte globulin, busulfan, and fludarabine preceded with 2 courses of pretransplant immunosuppressive therapy (PTIS) with fludarabine and dexamethasone. Graft-versus-host disease (GVHD) prophylaxis consisted of PTCY on days +3 and +4 followed by tacrolimus and mycophenolate mofetil starting on day +5. Four patients (ages 13, 19, 19, and 23 years) received T cell–replete haploidentical stem cell infusion. All patients engrafted with 99.9% to 100% donor chimerism, and all patients continued with stable engraftment at the last follow-up (5 to 11 months post-transplant). Time to neutrophil engraftment was 14 to 26 days. Two patients had high levels of donor-specific anti-HLA antibodies, which required the implementation of an antibody management protocol. This facilitated neutrophil engraftment on day +16 and day +26, respectively. One patient developed grade I acute GVHD, which resolved. Three patients developed mild, limited skin GVHD that responded to conventional immunosuppressive therapy. Human herpesvirus-6 viremia was detected in 3 patients but resolved without treatment. One patient developed asymptomatic cytomegalovirus viremia that responded appropriately to standard therapy with ganciclovir. The prompt, stable engraftment and low toxicity in the post-transplant period makes PTIS with haploidentical transplant a promising option for patients with SCD.     

Haploidentical Peripheral Blood Stem Cell Transplantation Demonstrates Stable Engraftment in Adults with Sickle Cell Disease

We report on the screening and development of haploidentical hematopoietic stem cell transplantation (HSCT) for adult patients with clinically aggressive sickle cell disease (SCD) at our institution. Of 50 adult SCD patients referred for HSCT between January 2014 and March 2017, 20% were denied by insurance. Of 41 patients initially screened, 10% lacked an available haploidentical donor, 29% had elevated donor-specific antibodies (DSAs), and 34% declined to proceed to HSCT. All 10 patients who were transplanted received peripheral blood stem cells. The initial 2 were conditioned with alemtuzumab/total body irradiation (TBI) 3?Gy followed by post-transplant cyclophosphamide and failed to engraft. The next 8 patients received the regimen developed at Johns Hopkins University with TBI 3?Gy. Granulocyte colony-stimulating factor was administered from day +12 in those with HbS < 30%. All 8 patients engrafted with a median time to neutrophil >.5 × 10⁹/L of 22 days (range, 18 to 23). One patient subsequently lost the graft, and 7 (87.5%) maintained >95% donor cell chimerism at 1-year post-HSCT. Two patients developed acute graft-versus-host disease (GVHD) of at least grade II. One had chronic GVHD and died >1 year after HSCT of unknown causes. With a median follow-up of 16 months (range, 11 to 29), 7 patients (87.5%) are alive. Our findings suggest that limited insurance coverage, high rate of DSAs, and patient declining HSCT may limit the availability of haploidentical HSCT in adult SCD patients. The modified Hopkins regimen used here demonstrates high engraftment and low morbidity rates and should be tested in larger, multicenter, prospective clinical trials.     

T Cell Repertoire Evolution after Allogeneic Bone Marrow Transplantation: An Organizational Perspective

High-throughput sequencing (HTS) of human T cell receptors has revealed a high level of complexity in the T cell repertoire, which makes it difficult to correlate T cell reconstitution with clinical outcomes. The associations identified thus far are of a broadly statistical nature, precluding precise modeling of outcomes based on T cell repertoire development following bone marrow transplantation (BMT). Previous work has demonstrated an inherent, mathematically definable order observed in the T cells from a diverse group of donors, which is perturbed in recipients following BMT. In this study, T cell receptor (TCR)-β sequences from HLA-matched related donor and recipient pairs are analyzed to further develop this methodology. TCR-β sequencing from unsorted and sorted T cell subsets isolated from the peripheral blood samples of BMT donors and recipients show conservation and symmetry of VJ segment usage in the clonal frequencies, linked to the organization of the gene segments along the TCR locus. This TCR-β VJ segment translational symmetry is preserved post-transplantation and even in cases of acute graft-versus-host disease (aGVHD), suggesting that GVHD occurrence represents a polyclonal donor T cell response to recipient antigens. The complexity of the repertoire is significantly diminished after BMT, and the T cell clonal hierarchy is altered post-transplantation. Low-frequency donor clones tended to take on a higher rank in the recipients following BMT, especially in patients with aGVHD. Over time, the repertoire evolves to a more donor-like state in the recipients who did not develop GVHD as opposed to those who did. The results presented here support new methods of quantifying and characterizing post-transplantation T cell repertoire reconstitution.     

Treatment of Leukemia by Alloreactive Lymphocytes and Nonmyeloablative Stem Cell Transplantation

Allogeneic bone marrow or blood stem cell transplantation (BMT) represents an important therapeutic tool for treatment of otherwise incurable malignant and nonmalignant diseases, especially acute and chronic leukemias. Until recently, myeloablative regimens were considered mandatory for effective eradication of all malignant cells of host origin. Our preclinical and ongoing clinical studies indicated that eradication of host immunohematopoietic cells, including chemoradiotherapy-resistant leukemia, could be achieved by adoptive allogeneic cell therapy with donor lymphocyte infusion following induction of host-versus-graft transplantation tolerance mediated by engraftment of donor stem cells in the course of BMT. Thus, eradication of blood cancer cells, especially in patients with chronic myeloid leukemia and less frequently in patients with other hematologic malignancies, could be frequently accomplished despite complete resistance of such tumor cells to maximally tolerated doses of chemoradiotherapy. Our cumulative experience suggested that graft-versus-leukemia (GVL) effects might be a useful tool for both treatment and prevention of relapse. Based on the aforementioned rationale, we speculated that the therapeutic benefit of BMT may be improved by using a safer conditioning as part of the transplant procedure, with the goal in mind to induce host-versus-graft tolerance to enable subsequent induction of GVL effects rather than attempt to eliminate host cells with hazardous myeloablative chemoradiotherapy. The latter hypothesis suggested that effective BMT procedure may be accomplished without lethal conditioning of the host, using a new well-tolerated nonmyeloablative regimen, thus possibly minimizing immediate and late side effects related to myeloablative procedures considered until recently mandatory for conditioning of BMT recipients. Recent clinical observations suggest that effective treatment of leukemia may be accomplished with a well-tolerated nonmyeloablative stem cell transplantation (NST) regimen, while avoiding immediate and late toxicity and minimizing procedure-related mortality. Taken together, our cumulative data suggest that high-dose chemotherapy and radiation therapy may be successively replaced by a more effective biological tool—alloreactive donor lymphocytes—thus setting the stage for innovative immunotherapeutic procedures for more selective and effective treatment of patients in need of BMT, including those resistant to conventional chemoradiotherapy.     

Single Infusion of Donor Mononuclear Early Apoptotic Cells as Prophylaxis for Graft-versus-Host Disease in Myeloablative HLA-Matched Allogeneic Bone Marrow Transplantation: A Phase I/IIa Clinical Trial

Because of its potent immunomodulatory effect, an infusion of donor mononuclear early apoptotic cells (ApoCell) was tested in addition to cyclosporine and methotrexate as prophylaxis for acute graft-versus-host disease (GVHD) after HLA-matched myeloablative allogeneic hematopoietic stem cell transplantation (HSCT) from a related donor. In a phase I/IIa clinical trial, we treated 13 patients (median age, 37 years; range, 20 to 59 years) with hematologic malignancies: 7 patients with acute lymphoblastic leukemia, 5 patients with acute myeloid leukemia, and 1 patient with chronic myeloid leukemia, who received conventional myeloablative conditioning, with 35, 70, 140, or 210 × 10⁶ cell/kg of donor ApoCell, on day -1 of transplantation. Engraftment was successful in all patients with median time to neutrophil recovery of 13 days (range, 11 to 19), and platelet recovery of 15 days (range, 11 to 59). Serious adverse effects were reported on 10 occasions in the trial, all of which were considered unrelated (n = 7) or unlikely to be related (n = 3) to ApoCell infusion. The nonrelapse mortality at day 100 and 180 after transplantation was 7.7% and the overall survival at 100 and 180 days after transplantation was 92% and 85%, respectively. All ApoCell preparations showed an in vitro significant tolerogenic effect upon interaction with dendritic cells. The overall incidence of acute grades II to IV GVHD was 23%, whereas among those receiving the 2 higher doses (n = 6), the rate was 0%. These results suggest that a single infusion of donor ApoCell in HLA-matched allogeneic HSCT is a safe and potentially effective prophylaxis for acute GVHD occurring after myeloablative conditioning. No dose limiting toxicity was observed. (Clinicaltrials.gov no. NCT00524784).     

Total Marrow Lymphoid Irradiation/Fludarabine/ Melphalan Conditioning for Allogeneic Hematopoietic Cell Transplantation

Reduced-intensity conditioning (RIC) regimens for hematopoietic stem cell transplantation (HCT) can reduce morbidity and mortality, but patients with advanced disease may require alternative approaches. In an initial report of RIC with fludarabine (FLU) and melphalan (MEL) with total marrow lymphoid irradiation (TMLI) in HCT for advanced hematologic malignancies in 33 patients, we found that the addition of TMLI to RIC was feasible and safe. Here we report long-term outcomes for these patients. This prospective study included 61 patients treated with TMLI to a dose of 12?Gy (1.5?Gy twice daily for 4 days), FLU (25?mg/m²/day for 5 days), and MEL (140?mg/m²/day for 1 day). Overall survival (OS), event-free survival (EFS), cumulative incidence of relapse (CIR), and nonrelapse mortality (NRM) were measured from the date of HCT. Survival outcomes were analyzed using Kaplan-Meier analysis. Patients were categorized as low/intermediate or high/very high risk using the Disease Risk Index. The median follow-up was 7.4 years. The majority of patients had acute leukemia (72%); 49% had high/very high-risk disease. The median patient age was 55 years (range, 9-70 years). Two-year OS, EFS, CIR, and NRM were 54% (95% confidence interval [CI], 41%-66%), 49% (95% CI, 36%-61%), 21% (95% CI, 13%-35%), and 30% (95% CI, 20%-43%), respectively. Five-year OS, EFS, CIR, and NRM were 42% (95% CI, 30%-54%), 41% (95% CI, 28%-53%), 26 (95% CI, 17%-40%), and 33% (95% CI, 23%-47%, respectively). Acute (any grade) and chronic (limited or extensive) graft-versus-host disease occurred in 69% and 74% of patients, respectively. The most common toxicity was mucositis. The addition of TMLI to FLU/MEL conditioning was well tolerated, with favorable outcomes. Dosage escalation of TMLI or other modifications may be needed to improve disease control.     

Preclinical Canine Model of Graft-versus-Host Disease after In Utero Hematopoietic Cell Transplantation

In utero hematopoietic cell transplantation (IUHCT) offers the potential to achieve allogeneic engraftment and associated donor-specific tolerance without the need for toxic conditioning, as we have previously demonstrated in the murine and canine models. This strategy holds great promise in the treatment of many hematopoietic disorders, including the hemoglobinopathies. Graft-versus-host disease (GVHD) represents the greatest theoretical risk of IUHCT and has never been characterized in the context of IUHCT. We recently described a preclinical canine model of IUHCT, allowing further study of the technique and its complications. We aimed to establish a threshold T cell dose for IUHCT-induced GVHD in the haploidentical canine model and to define the GVHD phenotype. Using a range of T cell concentrations within the donor inoculum, we were able to characterize the phenotype of IUHCT-induced GVHD and establish a clear threshold for its induction between 3% and 5% graft CD3⁺ cell content. Given the complete absence of GVHD at CD3 doses of 1% to 3% and the excellent engraftment with the lowest dose, there is a safe therapeutic index for a clinical trial of IUHCT.     

Patient Perspectives Regarding Allogeneic Bone Marrow Transplantation in Myelofibrosis

Hematopoietic stem cell transplantation (HCT) is a curative treatment for patients with myelofibrosis (MF); however, many HCT-eligible patients decline this potentially life-saving procedure. The reasons behind this decision are not clear. We sought to survey patients with MF to understand their perspective on HCT. A 63-question survey was posted on myeloproliferative neoplasm patient advocacy websites. A total of 129 patients with MF responded to the survey. Among these patients, 49 (41%) were referred for HCT, and 41(32%) attended the transplantation consult. Of the patients who attended the transplantation consult, 24 (59%) did not plan on going on to HCT, and 16 (41%) intended to proceed with HCT. Reasons for the decision to not undergo transplantation included the desire to not be ill, desire to not spend time in the hospital, and concerns about overall quality of life. Specifically, concerns related to financial impact and the risk of graft-versus-host disease (GVHD) were expressed. Patients who decided to proceed with HCT felt that this would extend their survival and allow them to be around family for longer. This is the first survey to investigate patient perceptions regarding HCT for MF. Less than one-half of the patients were referred for HCT, and of those, less than one-half planned on proceeding with the transplantation, suggesting that many patients do not receive this life-saving procedure. Further exploration of the basis of patients’ reluctance to proceed with HCT is warranted.