Durable engraftment after pharmacological pre-transplant immune suppression followed by reduced-toxicity myeloablative haploidentical stem cell transplantation in highly HLA-immunized adults with sickle cell disease.

Allogeneic stem cell transplantation (Allo-SCT) is the only rapidly available curative treatment modality in patients with severe sickle cell disease (SCD). The development of reduced-toxicity myeloablative conditioning (RT-MAC) regimen and the use of partially matched family donors with post-transplantation cyclophosphamide (PT-Cy) have widened the access to Allo-SCT. Antibodies against donor-specific HLA (DSA) increase the risk of engraftment failure in HLA mismatched Allo-SCT. We report the results of five patients with SCD, whereas three with DSA, who underwent an unmanipulated haploidentical stem cell transplantation (Haplo-SCT) after a busulfan-based RT-MAC regimen with PT-Cy. To reduce the risk of engraftment failure, a sequential two courses pharmacological pre-transplant immune suppression (PTIS) phase was added prior to the conditioning regimen. All patients engrafted successfully. The procedure was well tolerated. None of the patients developed acute GVHD, whereas one developed moderate chronic GVHD. After a median follow-up of 5 years (range, 2.2-9), all patients are free of pain with excellent quality of life. Our report shows that Haplo-SCT after a RT-MAC regimen is feasible and safe with stable long-term engraftment and excellent disease control. The risk of graft failure can be abrogated by adding a PTIS phase prior to initiating the conditioning regimen.

Peripheral blood haploidentical hematopoietic cell transplantation for patients aged 70 years and over with acute myeloid leukemia or high-risk myelodysplastic syndrome.

Haploidentical stem cell transplantation (Haplo-SCT) using non-myeloablative conditioning regimen (NMAC) has extended the feasibility of allogeneic transplantation, notably in older patients. However, there is few data specifically focusing on patients aged 70 years and over with AML and MDS. Thus the benefit of transplantation in this population is still debated. Here we report our single center experience of peripheral blood Haplo-SCT with NMAC and post-transplantation cyclophosphamide in AML and MDS patients aged 70 years and over. We analyzed 50 patients (27 AML, 23 MDS) with a median age of 72 years (70-77), 12/50 (24%) with active disease at Haplo-SCT. Cumulative incidence of grade 3-4 acute and moderate or severe chronic GVHD were 6% and 25%, respectively. Non-relapse mortality (NRM) at day +100 was 0%. NRM, relapse, PFS and OS at 3 years were 16%, 18%, 66%, and 69%, respectively. Among patients who were disease free at 2 years post Haplo-SCT, 88% are living without immunosuppressive treatment. Peripheral blood Haplo-SCT is feasible in selected AML/MDS patients over 70 years, without any early NRM. It produces long-term disease control and survival. Thus, age by itself should not be considered as a formal barrier to Haplo-SCT.

[Method and impact of allografts cryopreservation during the Covid-19 pandemic: guidelines from the SFGM-TC]. / Modalités et impact de la cryopréservation des greffons allogéniques en contexte pandémique : recommandations de la SFGM-TC.

The COVID-19 pandemic disorganized the allogeneic stem cell transplantation activities all over the world, with the necessity to cryopreserve allografts to secure the procedure for both the recipient and the donor. Cryopreservation, usually anecdotal, has been used by all the French speaking centers; data collected from 24 centers were assessed in order to determine the impact of cryopreservation on the quality of allografts. Our analysis clearly demonstrates that increasing transit time (more than 48hours) is deleterious for CD34+ recovery, legitimates the slight increase of the requested CD34+ cell dose with respect to the average recovery rate as well as the importance of the quality control on the infused product.

Sepax-2 cell processing device: a study assessing reproducibility of concentrating thawed hematopoietic progenitor cells.

BACKGROUND: Autologous hematopoietic progenitor cell (HPC) transplantation is currently the standard of care for a fraction of patients with newly diagnosed myelomas and relapsed or refractory lymphomas. After high-dose chemotherapy, cryopreserved HPC are either infused directly after bedside thawing or washed and concentrated before infusion. We previously reported on the comparability of washing/concentrating HPC post-thaw vs. infusion without manipulation in terms of hematopoietic engraftment, yet settled for the prior favoring cell debris and DMSO removal. For almost two decades, automation of this critical step of washing/concentrating cells has been feasible. As part of continuous process verification, we aim to evaluate reproducibility of this procedure by assessing intra-batch and inter-batch variability upon concentration of thawed HPC products using the Sepax 2 S-100 cell separation system. METHODS: Autologous HPC collected from the same patient were thawed and washed either in two batches processed within a 3-4 h interval and immediately infused on the same day (intra-batch, n = 45), or in two batches on different days (inter-batch, n = 49) for those patients requiring 2 or more high-dose chemotherapy cycles. Quality attributes assessed were CD34+ cell recovery, viability and CD45+ viability; CFU assay was only performed for allogeneic grafts. RESULTS: Intra-batch and inter-batch median CD34+ cell recovery was comparable (75% vs. 73% and 77% vs. 77%, respectively). Similarly, intra-batch and inter-batch median CD45+ cell viability was comparable (79% vs. 80% and 79% vs. 78%, respectively). Bland-Altman analysis describing agreement between batches per patient revealed a bias close to 0%. Additionally, lower HPC recoveries noted in batch 1 were noted as well in batch 2, regardless of the CD34+ cell dose before cryopreservation, both intra- and inter-batch, suggesting that the quality of the collected product plays an important role in downstream recovery. Intrinsic (high mature and immature granulocyte content) and extrinsic (delay between apheresis and cryopreservation) variables of the collected product resulted in a significantly lower CD45+ viability and CD34+ cell recovery upon thawing/washing. CONCLUSIONS: Automated post-thaw HPC concentration provides reproducible cell recoveries and viabilities between different batches. Implications of this work go beyond HPC to concentrate cell suspension/products during manufacturing of cell and gene therapy products.

Phase I Trial of Prophylactic Donor-Derived IL-2-Activated NK Cell Infusion after Allogeneic Hematopoietic Stem Cell Transplantation from a Matched Sibling Donor.

Background: NK cell-based immunotherapy to prevent relapse after allogeneic transplantation is an appealing strategy because NK cells can provide strong antitumor effect without inducing graft-versus-host disease (GVHD). Thus, we designed a phase-I clinical trial evaluating the safety of a prophylactic donor-derived ex vivo IL-2 activated NK cell (IL-2 NK) infusion after allo-HSCT for patients with hematologic malignancies. Methods: Donor NK cells were purified and cultured ex vivo with IL-2 before infusion, at three dose levels. To identify the maximum tolerated dose was the main objective. In addition, we performed phenotypical and functional characterization of the NK cell therapy product, and longitudinal immune monitoring of NK cell phenotype in patients. Results: Compared to unstimulated NK cells, IL-2 NK cells expressed higher levels of activating receptors and exhibited increased degranulation and cytokine production in vitro. We treated 16 patients without observing any dose-limiting toxicity. At the last follow up, 11 out of 16 treated patients were alive in complete remission of hematologic malignancies without GVHD features and immunosuppressive treatment. Conclusions: Prophylactic donor-derived IL-2 NK cells after allo-HSCT is safe with low incidence of GVHD. Promising survivals and IL-2 NK cell activated phenotype may support a potential clinical efficacy of this strategy.

Validation of a flow cytometry-based method to quantify viable lymphocyte subtypes in fresh and cryopreserved hematopoietic cellular products.

BACKGROUND AIMS: Adoptive cellular therapy with immune effector cells (IECs) has shown promising efficacy against some neoplastic diseases as well as potential in immune regulation. Both inherent variability in starting material and variations in cell composition produced by the manufacturing process must be thoroughly evaluated with a validated method established to quantify viable lymphocyte subtypes. Currently, commercialized immunophenotyping methods determine cell viability with significant errors in thawed products since they do not include any viability staining. We hereby report on the validation of a flow cytometry-based method for quantifying viable lymphocyte immunophenotypes in fresh and cryopreserved hematopoietic cellular products. METHODS: Using fresh or frozen cellular products and stabilized blood, we report on the validation parameters accuracy, uncertainty, precision, sensitivity, robustness and contamination between samples for quantification of viable CD3+, CD4+ T cells, CD8+ T cells, CD3-CD56+CD16+/- NK cells, CD19+ B cells and CD14+ monocytes of relevance to fresh and cryopreserved hematopoietic cellular products using the Cytomics FC500 cytometer (Beckman Coulter). RESULTS: The acceptance criteria set in the validation plan were all met. The method is able to accommodate the variability in absolute numbers of cells in starting materials collected or cryopreserved from patients or healthy donors (uncertainty of ≤20% at three different concentrations), stability over time (compliance over 3 years during regular inter-laboratory comparisons) and confidence in meaningful changes during cell processing and manufacturing (intra-assay and intermediate precision of 10% coefficient of variation). Furthermore, the method can accurately report on the efficacy of cell depletion since the lower limit of quantification was established (CD3+, CD4+ and CD8+ cells at 9, 8 and 8 cells/µL, respectively). The method complies with Foundation for the Accreditation of Cellular Therapy (FACT) standards for IEC, FACT-Joint Accreditation Committee of ISCT-EBMT (JACIE) hematopoietic cell therapy standards, International Council for Harmonisation of Technical Requirements for Pharmaceuticals for Human Use Q2(R1) and International Organization for Standardization 15189 standards. Furthermore, it complies with Ligand Binding Assay Bioanalytical Focus Group/American Association of Pharmaceutical Scientists, International Council for Standardization of Hematology/International Clinical Cytometry Society and European Bioanalysis Forum recommendations for validating such methods. CONCLUSIONS: The implications of this effort include standardization of viable cell immunophenotyping of starting material for cell manufacturing, cell selection and in-process quality controls or dosing of IECs. This method also complies with all relevant standards, particularly FACT-JACIE standards, in terms of enumerating and reporting on the viability of the "clinically relevant cell populations."

[CD34+ cell selection methods, quality controls and expected results: Guidelines from the Francophone Society of Bone Marrow Transplantation and Cellular Therapy (SFGM-TC)]. / Procédé de préparation, contrôles de qualité et spécifications des immunosélections CD34+ : recommandations de la Société francophone de greffe de moelle et de thérapie cellulaire (SFGM-TC).

CD34+ immunomagnetic positive selection allows for CD34+ hematopoietic progenitors separation from CD3+ lymphocytes subsets, usually from an apheresis product collected from a previously mobilized donor. This T-cell depleted stem cell graft is primarily intended for rare cases (around 2% of allotransplanted patients in France) of severe, persistent, symptomatic bi- or tri-cytopenia post-allotransplantation, in order to allow for hematologic reconstitution without increasing the risk of GvHD occurrence. Although semi-manual and complex, the process is of sufficient robustness to consistently generate a cellular product with distinctive features and specifications, based on iterative in-process quality controls, that are discussed within these guidelines.

Checkpoint inhibition before haploidentical transplantation with posttransplant cyclophosphamide in Hodgkin lymphoma.

We report on 59 Hodgkin lymphoma patients undergoing haploidentical stem cell transplantation (SCT; haplo-SCT) with posttransplant cyclophosphamide (PTCy) as graft-versus-host disease (GVHD) prophylaxis, comparing outcomes based on pretransplant exposure to checkpoint inhibitors (CPIs). Considering pretransplant characteristics, the 2 cohorts (CPI = 29 patients vs no-CPI = 30 patients) were similar, except for the number of prior lines of therapy (6 vs 4; P < .001). With a median follow-up of 26 months (range, 7.5-55 months), by univariate analysis, the 100-day cumulative incidence of grade 2-4 acute GVHD was 41% in the CPI group vs 33% in the no-CPI group (P = .456), whereas the 1-year cumulative incidence of moderate to severe chronic GVHD was 7% vs 8%, respectively (P = .673). In the CPI cohort, the 2-year cumulative incidence of relapse appeared lower compared with the no-CPI cohort (0 vs 20%; P = .054). No differences were observed in terms of overall survival (OS), progression-free survival (PFS), and nonrelapse mortality (NRM) (at 2 years, 77% vs 71% [P = .599], 78% vs 53% [P = .066], and 15% vs 21% [P = .578], respectively). By multivariable analysis, CPI before SCT was an independent protective factor for PFS (hazard ratio [HR], 0.32; P = .037). Stable disease (SD)/progressive disease (PD) was an independent negative prognostic factor for both OS and PFS (HR, 14.3; P < .001 and HR, 14.1; P < .001, respectively) . In conclusion, CPI as a bridge to haplo-SCT seems to improve PFS, with no impact on toxicity profile.

Analysis of a large single institution cohort of related donors fails to detect a relation between SDF1/CXCR4 or VCAM/VLA4 genetic polymorphisms and the level of hematopoietic progenitor cell mobilization in response to G-CSF.

We studied a cohort of 367 healthy related donors who volunteered to donate their hematopoietic stem cells for allogeneic transplantation. All donors were homogeneously cared for at a single institution, and received rhG-CSF as a mobilization treatment prior to undergoing apheresis. Peripheral blood CD34+ cell counts were used as the main surrogate marker for rhG-CSF induced mobilization. We searched whether inter-individual variations in known genetic polymorphisms located in genes whose products are functionally important for mobilization, could affect the extent of CD34+ mobilization, either individually or in combination. We found little or no influence of individual SNPs or haplotypes for the SDF1, CXCR4, VCAM and VLA4 genes, whether using CD34+ cell counts as a continuous or a categorical variable. Simple clinical characteristics describing donors such as body mass index, age and possibly sex are more potent predictors of stem cell mobilization. The size of our cohort remains relatively small for genetic analyses, however compares favorably with cohorts analyzed in previously published reports suggesting associations of genetic traits to response to rhG-CSF; notwithstanding this limitation, our data do not support the use of genetic analyses when the choice exists of several potential donors for a given patient.

Posttransplantation cyclophosphamide vs. antithymocyte globulin as GVHD prophylaxis for mismatched unrelated hematopoietic stem cell transplantation.

Posttransplant cyclophosphamide (PT-Cy) is an efficient GVHD prophylaxis but has not been extensively evaluated in mismatched unrelated donor (MMUD) allo-HSCT, for which antithymocyte globulin (ATG) is still considered as a standard. Thus, we evaluated the outcome of MMUD allo-HSCT with PT-Cy (n = 22) and performed a historical comparison with a control group receiving ATG (n = 40) in a single center experience. Compared with the ATG group, the risk of grade 2-4 acute GVHD was significantly lower in the PT-Cy group (HR = 0.12, 95% CI = [0.03-0.48], p = 0.002). No difference was observed in the cumulative incidence of chronic GVHD. The risk of both NRM and relapse was significantly lower in the PT-Cy group (NRM: HR = 0.05, 95% CI = [0.00-0.63], p = 0.021; relapse: HR = 0.31; 95% CI = [0.09-1.10], p = 0.07). Thus, we observed significantly better PFS (HR = 0.22, 95% CI = (0.07-0.65); p = 0.006), OS (HR = 0.24, 95% CI = (0.07-0.84); p = 0.026), and GRFS (HR = 0.37, 95% CI = (0.17-0.80); p = 0.011) in the PT-Cy group. We conclude that PT-Cy is an effective GVHD prophylaxis in the setting of MMUD allo-HSCT, resulting in a better outcome compared with standard prophylaxis using ATG. This suggests that as it was shown in the setting of haploidentical allo-HSCT, the use of PT-Cy can overcome the impact of HLA disparity, leading to promising survivals that approach those observed after HLA matched allo-HSCT.

A matched-pair analysis reveals marginally reduced CD34+ cell mobilization on second occasion in 27 related donors who underwent peripheral blood stem cell collection twice at the same institution.

BACKGROUND: In a small proportion of cases, hematopoietic function is insufficient after allogeneic hematopoietic stem cell transplantation, as a result of poor graft function or graft failure. These complications are common indications of re-mobilization of the initial donor, either for a second allograft or for an infusion of CD34+ Selected stem Cell Boost (SCB). METHODS AND MATERIALS: We retrospectively reviewed the results of two cycles of CD34+ cell mobilization and collection. CD34+ cells mobilized and collected at each cycle were compared. When CD34+ cell selection from the collected allogeneic mononuclear cells was indicated, it was performed with the Clinimacs Plus® medical device, and results from in-process and final quality checks were analyzed. To assess the efficacy of CD34+ SCB, transfusion needs before and after the infusion of selected CD34+ cells were calculated. RESULTS: The median peripheral blood concentration of CD34+ cells/µL was marginally reduced during the second cycle (35.6 vs 33.8, p < 0.05); results revealed a strong correlation between paired values (r = 0.85). The cumulative number of collected CD34+ cells were similar for both cycles; the total processed blood volume was higher during the second cycle (p = 0.023). For CD34+ immune-selection procedures, CD34+ cell recovery and purity were respectively 57% and 95%, with a median T-cell depletion of 6.7 log. Recipients' needs for platelet and red blood cell transfusions were significantly reduced after CD34+ SCB. CONCLUSION: This study confirms the feasibility of a second cycle of mobilization in healthy related donors and the benefits of CD34+ SCB on hematopoietic reconstitution.

Epigenetic down-regulation of the HIST1 locus predicts better prognosis in acute myeloid leukemia with NPM1 mutation.

BACKGROUND: The epigenetic machinery is frequently altered in acute myeloid leukemia. Focusing on cytogenetically normal (CN) AML, we previously described an abnormal H3K27me3 enrichment covering 70 kb on the HIST1 cluster (6.p22) in CN-AML patient blasts. Here, we further investigate the molecular, functional, and prognosis significance of this epigenetic alteration named H3K27me3 HIST1 in NPM1-mutated (NPM1mut) CN-AML. RESULTS: We found that three quarter of the NPM1mut CN-AML patients were H3K27me3 HIST1high. H3K27me3 HIST1high group of patients was associated with a favorable outcome independently of known molecular risk factors. In gene expression profiling, the H3K27me3 HIST1high mark was associated with lower expression of the histone genes HIST1H1D, HIST1H2BG, HIST1H2AE, and HIST1H3F and an upregulation of genes involved in myelomonocytic differentiation. Mass spectrometry analyses confirmed that the linker histone protein H1d, but not the other histone H1 subtypes, was downregulated in the H3K27me3 HIST1high group of patients. H1d knockdown primed ATRA-mediated differentiation of OCI-AML3 and U937 AML cell lines, as assessed on CD11b/CD11c markers, morphological and gene expression analyses. CONCLUSIONS: Our data suggest that NPM1mut AML prognosis depends on the epigenetic silencing of the HIST1 cluster and that, among the H3K27me3 silenced histone genes, HIST1H1D plays a role in AML blast differentiation.

Validation of a semi automatic device to standardize quantification of Colony-Forming Unit (CFU) on hematopoietic stem cell products.

Accurate characterization of hematopoietic stem cells (HSC) products is needed to better anticipate the hematopoietic reconstitution and the outcome in patients. Although CD34+ viable cells enumeration is a key predictor of time to correction of aplasia, it does not fully inform about functionality of cells contained in the graft. CFU assay is the gold standard in vitro potency assay to assess clonogenicity of HSC and consists on the count and identification of colonies several days after culture in a semi solid media. Manual count of colonies with optic microscope is the most commonly used method but its important variability and subjectivity hinders the universal implementation of this potency assay. The aim of this study is to validate a standardized method using the STEMvision™ system, the first semi-automated instrument for imaging and scoring hematopoietic colonies, according to French and European recommendations. Results obtained highlight better performance criteria with STEMvision™ system than the manual method. This semi-automatic device tends to reduce the coefficients of variation of repeatability, inter-operator variability and intermediate precision. This newly available platform could represent an interesting option, significantly improving performances of CFU assays used for the characterization of hematopoietic progenitors.

Thiotepa, Fludarabine, and Busulfan Conditioning Regimen before T Cell-Replete Haploidentical Transplantation with Post-Transplant Cyclophosphamide for Acute Myeloid Leukemia: A Bicentric Experience of 100 Patients.

Haploidentical stem cell transplantation (haplo-SCT) with post-transplant cyclophosphamide (PT-Cy) is an alternative treatment for acute myeloid leukemia (AML) patients who lack HLA-matched donors. Relapse after haplo-SCT remains a major concern, especially after nonmyeloablative conditioning regimens. Promising results were reported for TBF-based conditioning regimens (thiotepa, busulfan, and fludarabine) in patients transplanted from different categories of donors and for various disease types but not specifically in PT-Cy haplo-SCT for AML. Here we evaluate the outcome of 100 AML patients who received haplo-SCT with PT-Cy after TBF conditioning regimens (reduced-intensity conditioning, n = 77; myeloablative conditioning, n = 23) in 2 transplant programs. Cumulative incidences of grades III to IV acute and moderate or severe chronic graft-versus-host disease (GVHD) were 7% and 14%, respectively. NRM at 2 years was 28%, significantly influenced by disease status at haplo-SCT (first complete response [CR1] versus advanced AML: 16% versus 38%, P = .016) but not by conditioning intensity or age. The cumulative incidences of relapse at 2 years were 17% and 24% in CR1 and advanced AML, respectively (not significant). Progression-free survival, overall survival, and GVHD and relapse-free survival at 2 years were 67%, 71%, and 49% in CR1 patients, respectively, whereas comparative values in patients with advanced disease were 37%, 41%, and 32%. Our study suggests that TBF conditioning for PT-Cy haplo-SCT is safe and effective for AML patients in CR1. In patients with more advanced disease, the relatively low incidence of relapse seems counterbalanced by a high nonrelapse mortality, underlining the need for alternative strategies to decrease relapse risk, without increasing the intensity of conditioning regimen.

Peripheral blood stem cell for haploidentical transplantation with post-transplant high dose cyclophosphamide: detailed analysis of 181 consecutive patients.

While bone marrow (BM) grafts were initially used for T-replete HLA-haploidentical related donors transplantation (Haplo-SCT) with post-transplantation cyclophosphamide (PT-Cy), the use of peripheral blood stem cell (PBSC) remains debated. We thus conducted a detailed analysis evaluating the incidence, risk factors, and prevalence of GVHD after PBSC Haplo-SCT with PT-Cy. One hundred and eighty-one patients with hematological diseases were included. Median time for neutrophil and platelet recovery was 21 and 30 days, respectively. The cumulative incidence of grade 3-4 acute GVHD and severe chronic GVHD were 8% and 4%, respectively, approaching what was observed after BM Haplo-SCT. NRM at 2 years was 21%, and 41% of the non-relapse deaths were caused by GVHD. The cumulative incidence of relapse at 2 years was 17% in the whole cohort, and 13% among AML patients (n = 54), suggesting a high GVL effect. As surrogate markers for good quality of life, we observed a 2-year GVHD-relapse-free survival probability of 50% and found that 6% and 2% of disease-free patients at 2 years were still living with GVHD and immunosuppressive treatments, respectively. Haplo-SCT with PT-Cy using PBSC grafts results in low incidence GVHD and promising disease control, making PBSCs a valuable alternative to BM graft in this setting.

Post-transplantation cyclophosphamide-based haploidentical versus Atg-based unrelated donor allogeneic stem cell transplantation for patients younger than 60 years with hematological malignancies: a single-center experience of 209 patients.

Allogeneic hematopoietic stem cell transplantation (allo-HSCT) is limited by availability of HLA-matched sibling donors (MSDs). The alternative use of unrelated donors (UDs) is currently challenged by haploidentical-related donors (HRDs). We retrospectively analyzed 209 consecutive patients younger than 60 years undergoing allo-HSCT from UDs (n = 128) or HRDs (n = 81). Cumulative incidences of grade 3-4 acute (17 vs. 2%, p = 0.003) and 2-year moderate and severe chronic (20 vs. 2%, p < 0.001) GVHD were significantly higher with UD. Progression-free survival (PFS) was significantly better with HRD (51 vs. 69%, p = 0.019), without significant difference in the cumulative incidence of relapse (CIR), non-relapse mortality (NRM), and overall survival (OS). Multivariate analyses confirmed the lower risk of acute and chronic GVHD (grade 2-4, HR = 0.43, p = 0.005; grade 3-4, HR = 0.20, p = 0.017; all grades, HR = 0.43, p = 0.012; moderate or severe, HR = 0.12, p = 0.004), better PFS (HR = 0.61, p = 0.046), and GRFS (HR = 0.47, p = 0.001) with HRD. This was confirmed in match-paired analysis. In the absence of MSDs, HRD could be considered as a suitable alternative for patients younger than 60 years.

[Donor Lymphocyte Infusions (DLI): Guidelines from the Francophone Society of Bone Marrow Transplantation and Cellular Therapy (SFGM-TC)]. / Injections de lymphocytes du donneur (DLI) : recommandations de la Société francophone de greffe de moelle et de thérapie cellulaire (SFGM-TC).

Donor lymphocyte infusion (DLI) can be proposed to treat or prevent the relapse of malignant hemopathies following allogeneic stem cell transplantation. The efficiency has been mainly reported in the treatment of CML and low-grade lymphomas while the anti-tumoral activity is less in forms of acute leukemia and myelodysplastic syndromes. The GVL benefit should always be compared to the possible toxic effects of GVHD. This article updates the initial SFGM-TC recommendations, proposed in 2013, that were focused on the use of DLI. Doses of DLI in the context of haplo-identical stem cell transplantation are now indicated. We confirm that remaining mobilized stem cells may be used as classical DLI. The definition and the place of preemptive and prophylactic DLI are precisely given. Recommendations regarding the quality of thawed DLI as well as necessary clinical and biological follow-up are also described in detail.

HLA-Matched Sibling versus Unrelated versus Haploidentical Related Donor Allogeneic Hematopoietic Stem Cell Transplantation for Patients Aged Over 60 Years with Acute Myeloid Leukemia: A Single-Center Donor Comparison.

Haploidentical related donor (HRD) allogeneic hematopoietic stem cell transplantation (allo-HSCT) was developed as a valid option for the treatment of acute myeloid leukemia (AML) in the absence of a matched donor. However, many investigators are reluctant to consider the use of this alternative in elderly patients, anticipating high morbidity. Here, we report a single-center comparison of HRD versus matched sibling donor (MSD) and unrelated donor (UD) allo-HSCT for patients with AML aged ≥60 years. Ninety-four patients (MSD: n = 31; UD: n = 30; HRD: n = 33) were analyzed. The median age was 65 (range, 60 to 73) years. We observed a higher cumulative incidence of grade 3 to 4 acute graft-versus-host disease (GVHD) after UD allo-HSCT (MSD versus UD versus HRD: 3% versus 33% versus 6%, respectively; P = .006). Two-year cumulative incidence of moderate or severe chronic GVHD was 17%, 27%, and 16% in the MSD, UD, and HRD groups, respectively (P = .487). No difference was observed in the 2-year cumulative incidence of relapse or nonrelapse mortality (NRM) (relapse: MSD versus UD versus HRD: 32% versus 25% versus 25%, respectively; P = .411; NRM: MSD versus UD versus HRD: 19% versus 27% versus 24%, respectively; P = .709). At 2 years, progression-free survival, overall survival, and GVHD- and relapse-free survival were 48%, 50%, and 39%, respectively, in the MSD group; 48%, 51%, and 23%, respectively, in the UD group; and 50%, 52%, and 32%, respectively, in the HRD group, without statistically significant differences between the groups. We conclude that HRD allo-HSCT is highly feasible and no less efficient than MSD or UD allo-HSCT in patients with AML aged ≥60 years. Thus, the absence of a HLA-identical donor should not limit the consideration of allo-HSCT for the treatment of AML.