Unmanipulated haplo-SCT Research Articles

Peritransplant glucocorticoids redistribute donor T cells to the bone marrow and prevent relapse after haploidentical SCT.

Patients with acute leukemia who are unable to achieve complete remission prior to allogeneic hematopoietic stem cell transplantation (SCT) have dismal outcomes, with relapse rates well in excess of 60%. Haplo-identical SCT (haplo-SCT) may allow enhanced graft-versus-leukemia (GVL) effects by virtue of HLA class I/II donor-host disparities, but it typically requires intensive immunosuppression with posttransplant cyclophosphamide (PT-Cy) to prevent lethal graft-versus-host disease (GVHD). Here, we demonstrate in preclinical models that glucocorticoid administration from days –1 to +5 inhibits alloantigen presentation by professional recipient antigen presenting cells in the gastrointestinal tract and prevents donor T cell priming and subsequent expansion therein. In contrast, direct glucocorticoid signaling of donor T cells promotes chemokine and integrin signatures permissive of preferential circulation and migration into the BM, promoting donor T cell residency. This results in significant reductions in GVHD while promoting potent GVL effects; relapse in recipients receiving glucocorticoids, vehicle, or PT-Cy was 12%, 56%, and 100%, respectively. Intriguingly, patients with acute myeloid leukemia not in remission who received unmanipulated haplo-SCT and peritransplant glucocorticoids also had an unexpectedly low relapse rate at 1 year (32%; 95% CI, 18%–47%) with high overall survival at 3 years (58%; 95% CI, 38%–74%). These data highlight a potentially simple and effective approach to prevent relapse in patients with otherwise incurable leukemia that could be studied in prospective randomized trials.

Haploidentical Stem Cell Transplantation for Acute Myeloid Leukemia: Current Therapies, Challenges and Future Prospective.

Haploidentical stem cell transplantation (haplo-SCT), an alternative donor source, offers a curative therapy for patients with acute myeloid leukemia (AML) who are transplant candidates. Advances in transplantation techniques, such as donor selection, conditioning regimen modification, and graft-versus-host disease prophylaxis, have successfully improved the outcomes of AML patients receiving haplo-SCT and extended the haploidentical transplant indictions for AML. Presently, treating de novo AML, secondary AML, therapy-related AML and refractory and relapsed AML with haplo-SCT can achieve comparable outcomes to those of human leukocyte antigen (HLA)-matched sibling donor transplantation (MSDT), unrelated donor transplantation or umbilical cord blood transplantation. For some subgroups of AML subjects, such as patients with positive pretransplantation minimal/measurable residual disease, recent studies suggest that haplo-SCT might be superior to MSDT in decreasing relapse and improving survival. Unfortunately, for patients with AML after haplo-SCT, relapse and infections remain the causes of death that restrict further improvement in clinical outcomes. In this review, we discuss the recent advances and challenges in haplo-SCT for AML treatment, mainly focusing on unmanipulated haplo-SCT protocols. We provide an outlook on future prospects and suggest that relapse prophylaxis, intervention, and treatment, as well as infection prevention and therapy, are areas of active research in AML patients who receive haploidentical allografts.

Donor-Specific Anti-HLA Antibodies in Haploidentical Stem Cell Transplantation with Post-Transplantation Cyclophosphamide: Risk of Graft Failure, Poor Graft Function, and Impact on Outcomes.

The presence of donor-specific anti-HLA antibodies (DSA) is associated with a 10-fold increased risk of graft failure in haploidentical stem cell transplantation (haplo-SCT). Consensus guidelines from the European Society for Blood and Marrow Transplantation set a mean fluorescence intensity (MFI) >1000 as a cutoff for DSA positivity. In the absence of an alternative donor, it is recommended that patients undergo desensitization therapy, especially with high DSA levels (>5000 MFI). The aim of this study was to analyze the impact of DSA on risk of graft failure and poor graft function, as well as on major outcomes in a consecutive cohort of patients who were systematically screened for DSA before haplo-SCT. A total of 141 consecutive patients were candidates for unmanipulated haplo-SCT with post-transplantation cyclophosphamide (PT-Cy) at our center between January 2012 and January 2018, and 135 were analyzed for the presence of HLA antibodies. Of these 134 patients underwent haplo-SCT. HLA antibodies were detected in 40 patients, including 19 with DSA and 21 without DSA. Ten of the 19 patients with DSA underwent transplantation using that donor, whereas 2 underwent a desensitization program before transplantation. Only 2 patients experienced primary graft failure (1.4 %), both of whom were without DSA. Twenty patients developed a poor graft function (15%). The 3-year overall survival (OS), 3-year progression-free survival (PFS), and 1-year nonrelapse mortality (NRM) were analyzed according to the presence or absence of DSA. No statistically significant difference was found. No impact of the presence of DSA on the risk of developing graft failure and poor graft function was revealed. Major outcomes of transplantation were analyzed separately in patients with poor graft function and those with good graft function. The 3-year OS, 3-year PFS, and 1-year NRM in good graft function and poor graft function populations were 62% versus 20% (P < .0001), 53% versus 20% (P < .0001), and 12% versus 40% (P = .009), respectively. The presence of low-level DSA in the absence of desensitization did not correlate with the risk of developing graft failure and poor graft function. Patients who experienced poor graft function had worse outcomes than patients with good graft function.

Platelet transfusion refractoriness after T-cell-replete haploidentical transplantation is associated with inferior clinical outcomes.

Haploidentical stem cell transplantation (haplo-SCT) has been an alternative source of bone marrow for patients without human leukocyte antigen (HLA)-matched donors. The aim of this study was to investigate the relationships between platelet transfusion refractoriness (PTR) and clinical outcomes in the setting of haplo-SCT. Between May 2012 and March 2014, 345 patients who underwent unmanipulated haplo-SCT were retrospectively enrolled. PTR occurred in 20.6% of all patients. Patients in the PTR group experienced higher transplant-related mortality (TRM, 43.7% vs. 13.5%, P<0.001), lower overall survival (OS, 47.9% vs. 76.3%, P<0.001) and lower leukemia-free survival (LFS, 47.9% vs. 72.3%, P<0.001) compared to patients in the non-PTR group. The multivariate analysis showed that PTR was associated with TRM (P=0.002), LFS (P<0.001), and OS (P<0.001). The cumulative incidences of PTR in patients receiving >12 platelet (PLT) transfusions (third quartile of PLT transfusions) were higher than in patients receiving either >6 (second quartile) or >3 (first quartile) PLT transfusions (56.1% vs. 41.6% vs. 28.2%, respectively; P<0.001). The multivariate analysis also showed that PTR was associated with the number of PLT transfusions (P<0.001). PTR could predict poor transplant outcomes in patients who underwent haploidentical SCT.

Single-agent GvHD prophylaxis with tacrolimus after post-transplant high-dose cyclophosphamide is a valid option for haploidentical transplantation in adults with hematological malignancies.

Eighty-one patients with high-risk hematological malignancies received unmanipulated haploidentical stem cell transplants (haploSCT) using the same protocol at four Spanish institutions. The conditioning regimen was thiotepa, busulfan and fludarabine; following bone marrow or peripheral blood infusion. GvHD prophylaxis with high-dose cyclophosphamide on days +3 and +4, and IV tacrolimus from day +5 was administered. 62% were in complete remission, 17% had received previous allogeneic SCT and 44% had a high-very high refined disease risk index. One patient had primary graft failure and three more died before +21. The median days to neutrophil and platelet recoveries were +18 and +23, respectively, and 93% achieved a full donor chimerism on day +30. At 1 year, cumulative incidences (CumInc) of non-relapse mortality and relapse were 27 and 19%. One-year overall survival and PFS were 61 and 51%. CumInc of grade II-IV and III-IV were 23 and 14%. At 30 months, CumInc of limited and extensive GvHD were 20 and 22%. In conclusion, patients with hematological malignancies who receive an unmanipulated haploSCT with post-transplant cyclophosphamide may benefit from less intense pharmacological prophylaxis for GvHD prophylaxis. Whether this approach potentiates the graft-versus-tumor effect and decreases relapses requires further investigation.

Optimal Dose of Antithymocyte Globulin in Conditioning Regimens for Unmanipulated Haploidentical Haematopoietic Stem Cell Transplantation: Long-Term Outcomes of a Prospective Randomised Trial

Background: Antithymocyte globulin (ATG) is an important component of conditioning regimens to prevent severe GVHD in patients undergoing unmanipulated haploidentical stem cell transplantation (haplo-SCT). However, the optimal dose of ATG is unknown.Methods: In this open-label extension of a prospective, randomised trial, we compared the long-term outcomes of two ATG doses used in myeloablative conditioning before unmanipulated haplo-HSCT. Patients were randomly assigned (1:1) to 10 mg/kg (ATG-10) or 6 mg/kg (ATG-6) ATG. Patients and individuals assessing outcomes were masked to treatment allocation. Analysis of disease-free survival (DFS), GVHD-free/relapse-free survival (GRFS), relapse, non-relapse mortality (NRM), and chronic GVHD (cGVHD) included the entire population. Late effects were assessed in disease-free patients who had survived for at least 6 months and had received regular follow-up evaluations.Results: Between December 2010 and May 2012, 224 patients were recruited. The median follow-up period was 1614 days (28-1929 days). The 5-year cumulative incidence was comparable between the ATG-6 and ATG-10 groups for relapse (12·8% vs. 13·4%, p=0·832) and NRM (11·6% vs. 17·0%, p=0·263). The 5-year probability of DFS was comparable between groups (75·6% vs. 69·6%, p=0·283). The 5-year cumulative incidence was higher with ATG-6 for cGVHD (75·0% vs. 56·3%, p=0·007; moderate-to-severe cGVHD: 56·3% vs. 30·4%, p<0·0001) and late effects (71·2% vs. 56·9%, p=0·043). The 5-year probability of GRFS was higher with ATG-10 (41·0% vs. 26·8%, p=0·008). In the multivariate analysis, ATG-10 was associated with lower cGVHD risk and improved GRFS.Conclusions: ATG 10 mg/kg may be the optimal dose for conditioning regimens before unmanipulated haplo-SCT. DisclosuresNo relevant conflicts of interest to declare.

Risk Factors and Outcome of Children with Relapsed/Refractory Acute Leukemia after T-Cell-Rich Haploidentical Hematopoietic Cell Transplantation

Background: T-cell rich (TCR) HLA-haploidentical SCT (haplo-SCT) is a form of T-cell therapy that has a high degree of efficacy in hematologic malignancies. Previously we reported the safety profile assessing GVHD prophylaxis that was conducted with anti-human thymocyte immunoglobulin (ATG), tacrolimus, methotrexate (MTX) and prednisolone (PSL) in unmanipulated haplo-SCT (Clin Transplant 2010, Transfus Med 2014). We evaluated efficacy and toxicity of TCR haplo-SCT in children with very high risk refractory/relapsed acute leukemia (VHR-R/R AL).Methods: VHR-R/R AL were defined as: relapse after SCT, very early or early relapse, induction failure(2 or more) and relapse of risk factor with MLL rearrangement, Ph+, Mo7 and 5q-. From Aug 2000 to April 2014, consecutive 38 patients (pts) with VHR-R/R AL who underwent TCR-haplo-SCT were included. The median age of pts was 8.2(0.3-19.1) years old. The diagnosis included ALL (n=27), AML (n=8), M/NKL (n=3). The disease status at TCR-haplo-SCT were 18 in CR (positive MRD: 8 pts), 20 in non-CR. HLA disparities were 2/8 in 1pt, 3/8 in 9 pts, 4/8 in 28 pts. Donors included fathers (n=21), mothers (n=14), and siblings (n=3). Thirty one pts received myeloablative conditioning (TBI based: 20 pts, Bu based: 11 pts) and 34 pts of them received ATG (rabbit, thymoglobulin 2.5mg/kg) containing regimen. The GVHD prophylaxis was conducted with tacrolimus, MTX and PSL. Thirty four pts received peripheral blood stem cells and 4 pts received BM.Results: Neutrophil engraftment (defined as >0.5x109/L) was 95% with a median day of 13 (range, 10-15). With a median 1640 days follow-up (range, 320-5510 days) in pts without events, the actuarial 3-year overall survival (OS) and disease-free survival (DFS) were 57% and 39%, respectively. On competing-risk analysis, 1-year cumulative incidences of grade II-IV acute GVHD and chronic GVHD were 71% and 63%, respectively; 3-year cumulative incidences of relapse and non-relapse mortality (NRM) were 40% and 20%. On univariate analysis, 3-year OS in pts with acute GVHD vs. without acute GVHD were 70% vs. 22% (p=.0006), in pts CR vs. non-CR at TCR-SCT were 83% vs. 32% (p=.007), in pts infused CD3 cell doses >=5 x 108/kg vs. <5 x 108/kg were 83% vs. 25% (p=.005), according to age at TCR-SCT <9 vs. >=9 were 79% vs. 34% (.008), respectively. In contrast, the occurrence of acute GVHD had no significant difference in infused CD3 cell doses.Conclusions: These data suggest that TCR haplo-SCT following low-dose ATG containing conditioning combined with our GVHD prophylaxis is well tolerated, facilitates engraftment, and has significant anti-leukemic activity, particularly in pediatric patients with refractory/ relapsed population. DisclosuresNo relevant conflicts of interest to declare.

How do we choose the best donor for T-cell-replete, HLA-haploidentical transplantation?

In haploidentical stem cell transplantations (haplo-SCT), nearly all patients have more than one donor. A key issue in the haplo-SCT setting is the search for the best donor, because donor selection can significantly impact the incidences of acute and chronic graft-versus-host disease, transplant-related mortality, and relapse, in addition to overall survival. In this review, we focused on factors associated with transplant outcomes following unmanipulated haplo-SCT with anti-thymocyte globulin (ATG) or after T-cell-replete haplo-SCT with post-transplantation cyclophosphamide (PT/Cy). We summarized the effects of the primary factors, including donor-specific antibodies against human leukocyte antigens (HLA); donor age and gender; killer immunoglobulin-like receptor-ligand mismatches; and non-inherited maternal antigen mismatches. We also offered some expert recommendations and proposed an algorithm for selecting donors for unmanipulated haplo-SCT with ATG and for T-cell-replete haplo-SCT with PT/Cy.

HLA Disparities Impact on Outcomes after Unmanipulated Haploidentical Hematopoietic Stem Cells Transplantation (HaploSCT) in Acute Leukemia: A Study from the Acute Leukemia Working Party of the European Group for Blood and Marrow Transplantation (EBMT)

Background: HaploSCT from unmanipulated graft is a practiced option for high risk acute leukemia (AL) patients (pts) who lack a matched related or unrelated donor (Piemontese, Leukemia 2015). Since several haploidentical donors are available for most pts, selection based on optimal HLA mismatching could be relevant, but evidence on this issue is scarce.We aimed to evaluate the impact of donor-recipient HLA mismatches (HLAmm) on unshared haplotype on HaploSCT outcomes, hypothesizing that the number of HLAmm and the different HLA loci involved could be associated with specific transplant-related risks.Methods: We retrospectively analyzed 490 pts with de novo acute myeloid leukemia (AML, n=346, 71%) and acute lymphoblastic leukemia (ALL, n=144, 29%) reported to EBMT, receiving a first unmanipulated peripheral blood (PB) or bone marrow (BM) HaploSCT between 2007 and 2014. Donor-recipient pairs were typed at a molecular low (n=323, 66%) or high (n=163, 34%) resolution level at HLA-A, -B, -C and -DRB1 loci. HLAmm were defined at antigen level.Results: Median follow-up was 17 (1.3-84) months; median age at transplant was 44 (18-78) years (y). Three hundred-ten pts (63%) were in complete remission (34% CR1, 29% CR2), 180 pts in advanced phase (CR3 and above, relapse or primary induction failure). Conditioning regimen was reduced intensity (RIC) in 48% of pts and myeloablative in 52%. Source of stem cells was PB for 61% of them, BM for 39%. In vivo T cell depletion (ATG or Campath) was used in 33% of pts and 56% of pts received high-dose post-transplant Cyclophosphamide (PTCy) for GVHD prophylaxis. Median donors' age was 38 (12-71) y. CMV donor/host status was neg/neg for 11% of pts, pos/neg for 6%, neg/pos for 19%, pos/pos for 62%.Of the 490 donor-recipient pairs, 55% had 4 HLAmm on unshared haplotype, 30% had 3 HLAmm, 12% had 2 HLAmm, 3% had 1 HLAmm. Among pairs with less than 4 HLAmm, 17% were matched at locus A, 12% at locus B, 19% at locus C, 16% at locus DRB1.Overall, 92% of pts achieved neutrophil engraftment at a median of 18 (12-63) days (d). At 100 d, cumulative incidence (CI) of grade ≥2 acute GvHD (aGvHD) was 33±4%. The 2-y CI of chronic GvHD (cGvHD), relapse (RI) and non-relapse mortality (NRM) were 30±4%, 37±5% and 29±4%, respectively. The probabilities of leukemia-free survival (LFS) and overall survival (OS) at 2 y were 34±5% and 39±5% respectively.In multivariate analysis, increasing number of HLAmm on unshared haplotype was not an independent prognostic factor for aGvHD (HR 0.8, p 0.2), cGvHD (HR 1.3, p 0.3), NRM (HR 1.3, p 0.3), RI (HR 1.1, p 0.6), LFS (HR 1.2, p 0.3) and OS (HR 1.3, p 0.2).Focusing on single HLA loci, match at HLA B locus on unshared haplotype was associated with lower 2y NRM in univariate analysis (17±8% in matched pairs, 31±11% in mismatched pairs, p 0.02), and this was confirmed in multivariate analysis (HR 0.5, p 0.04) accounting for all known risk factors (AL type, disease status, conditioning regimen intensity, host/donor age and sex, GvHD prevention, CMV status, number of HaploSCT performed in each center).Moreover, donor-recipient pairs matched at HLA DRB1 locus on unshared haplotype had lower rates of 100d CI of grade ≥2 aGvHD (20±8% in matched pairs, 34±4% in mismatched pairs, p 0.01), and this proved to be an independent factor in multivariate analysis (HR 0.5, p 0.02).Among other relevant factors, diagnosis of AML was associated with higher probabilities of LFS and OS (HR=0.6, p<10e-3 and HR=0.5, p<10e-4 respectively) and lower RI and NRM (HR=0.6, p=0.001 and HR=0.7, p=0.02 respectively). Advanced disease was a risk factor for LFS and OS (HR=3.4, p<10e-14 and HR=3.5, p<10e-12 respectively) as for RI and NRM (HR=6.1, p<10e-14 and HR=1.7, p=0.01 respectively). Significant factors for aGvHD were: PB as stem cell source (HR 1.9, p<10e-3), CMV status neg/neg (HR 0.5, p 0.02) and RIC (HR 0.7, p 0.02). PTCy and RIC regimen were the only independent significant factors for cGvHD (HR=0.6, p=0.01 and HR=0.6, p=0.002 respectively).Conclusions: In our series of 490 AL pts, number of HLAmm on unshared haplotype did not influence outcomes of unmanipulated HaploSCT. However, a match at HLA-B and HLA-DRB1 loci on unshared haplotype was associated with lower NRM and lower risk of grade 2-4 aGvHD, respectively.If further validated, our data could drive a more accurate selection of haploidentical donors in non T-cell depleted HaploSCT, accounting for potential biological implications of HLA locus-specific differences. DisclosuresTischer:Sanofi-Aventis: Other: advisory board. Nagler:Novaratis Pharmaceuticals Corporation: Consultancy, Honoraria, Research Funding. Mohty:Janssen: Honoraria; Celgene: Honoraria.

A survey on unmanipulated haploidentical hematopoietic stem cell transplantation in adults with acute leukemia.

The use of unmanipulated graft is increasingly adopted in the setting of allogeneic hematopoietic stem cell transplantation from haploidentical family donors (haplo-SCT) in acute leukemia (AL). We analyzed the outcome of 229 adult patients with de novo AL, who received an unmanipulated haploidentical transplant as their first allo-SCT between 2007 and 2011. Median follow-up was 30 months. Disease status at transplant was: first complete remission (CR1) for 77, second CR (CR2) for 56, and advanced for 96 patients. One hundred and seventy-one patients received in vivo T-cell depletion by monoclonal antibodies (75%). The 60-day cumulative incidence (CI) of engraftment was 93±2%. The 100-day CI of acute graft-versus-host disease (GvHD) was 32±3% for grade II-IV, 12±3% for grade III-IV. The 3-year CI of chronic GvHD was 34±3%. The 3-year CI of non-relapse mortality was 31±4% with in vivo T-cell depletion and 17±5% without. At 3 years, for patients transplanted in CR1, CR2 or advanced disease leukemia-free survival was 44±6, 42±7 and 12±3%, overall survival was 55±6, 51±7 and 14±4% and CI of relapse was 32±6, 24±6 and 61±5%, respectively. These data suggest that unmanipulated haplo-SCT is a valid treatment option for adult AL patients in complete remission lacking a matched donor.

Unmanipulated HLA-Haploidentical (2-3 antigen-mismatched) Stem Cell Transplantation Using Myeloablative or Reduced-Intensity Preconditioning Regimen,

Abstract 4117Related haploidentical donors, as cord blood, can be alternative donor sources in stem cell transplantation (SCT). Severe GVHD, however, has interfered the progress of haploidentical SCT (haploSCT). To deal with this strong GVHD, T cell depletion has usually been used in US and European countries. In order to pursue the controllable GVL effect by T cells, we have performed unmanipulated haploSCT using myeloablative or reduced intensity preconditioning regimen accompanied with intensified GVHD prophylaxis, including steroids. In this meeting, we will summarize our experience of haploSCT for more than ten years. From August 1998 to September 2010, we have performed 351 cases of haploSCT (all cases were HLA 2–3 antigen mismatched in GVH direction). Patients’ characteristics are sex: male 186, female 168, age: 16–65 years old (median 39), disease: AML/MDS 149, ALL 81, ML 67, others 54. Eighty-three percent of cases underwent SCT in non-complete remission (non-CR) status. Patients under 45 years old underwent myeloablative preconditioning regimen consisting of FLU/CA/CY/TBI 8Gy (haplo-full, n=100), and patients over 45 years old or with comorbidities or repetitive SCT (including second to fifth SCT) underwent reduced intensity preconditioning regimen consisting of FLU/(CA)/BU/ATG or FLU/(CA)/MEL/ATG (haplo-mini, n=251). High dose Ara-C (CA) was optional to reduce tumor burden. As ATG, ATG (Fresenius) 8mg/kg, or thymoglubulin (genzyme) 2–4mg/kg were integrated into conditioning treatments mainly for reduced-intensity transplantation. GVHD prophylaxis consisted of taclolimus (TAC), methylprednisolone (mPSL) 2mg/kg/day, short term MTX, and mycophenolate mofetil (MMF) 15mg/kg/day in haplo-full, and TAC, and mPSL 1mg/kg/day in haplo-mini, respectively. For elderly patients over 50 years old in haplo-mini, MMF was added. Hematopoietic engraftment in haploSCT was as rapid as that in HLA-identical SCT, except 10 cases of graft rejection. The median time to reach a neutrophil account of >0.5 × 109/l was 10 days for haplo-mini and 13 days for haplo-full. Platelet recovery was achieved in 66 % and 60% of patients undergoing haplo-mini and haplo-full, respectively. The median time to reach a nontransfused platelet count of 3 20 × 109/l was 22 days for haplo-mini and 33 days for haplo-full. Sixty percent of haplo-mini patients and 54 % of haplo-full patients did not develop acute GVHD. Acute GVHD (grade II-IV) was observed in 20% for haplo-mini and 36 % for haplo-full. Overall survival at five years was 30% for haplo-full and 40% for haplo-mini, respectively. If limited to CR cases, overall survival reached over 60% in haplo-mini. There is no difference in survival rate among patients’ diseases. In multivariate analysis on survival using variables, including disease status before transplantation, haplo-full vs haplo-mini, mismatches in GVH direction, mismatches in HVG direction, patients’ age, and the number of transplantation times, the disease status (CR) was found to be only a significantly favorable factor (P= 0.0026). Unmanipulated haploSCT is feasible and effective for refractory diseases. ATG dose used in haplo-mini is critical, and rather low compared with that of European cases reported so far. Although it should be too early to refer long term outcome, unmanipulated haploSCT could be considered as an option to control refractory diseases. Disclosures:No relevant conflicts of interest to declare.

Risk and prevention of graft failure in patients with preexisting donor-specific HLA antibodies undergoing unmanipulated haploidentical SCT

A role of donor-specific HLA antibodies (DSA) in graft failure after SCT has been suggested, but the relevance of DSA in unmanipulated haploidentical SCT (haplo-SCT) remains unknown. We prospectively examined HLA antibodies using the Luminex-based single Ag assay for 79 adult patients undergoing unmanipulated haplo-SCT. Among them, 16 (20.2%) were HLA Ab-positive, including five patients with antibodies not corresponding to donor HLA Ags and 11 DSA-positive patients. Of the 11 DSA-positive patients, five received treatments to decrease DSA levels, including two, who received plasma exchange and rituximab, two who received platelet transfusions from healthy-related donors having DSA-corresponding HLA Ags and one who received bortezomib. Platelet transfusion was the most simple and effective treatment option for class I DSA. The cumulative incidence of neutrophil recovery was significantly lower in pretransplant (post-treatment) DSA-positive patients than in DSA-negative patients (61.9 vs 94.4%, P=0.026). Notably, three of five patients with high levels of DSA had graft failure. Donors should be selected on the basis of an evaluation of HLA antibodies. If haplo-SCT from donors with HLA Ags that correspond to high levels of DSA must be performed, then recipients should be treated for DSA to improve the chances of successful donor engraftment.