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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., (Copyright © 2019 American Society for Blood and Marrow Transplantation. Published by Elsevier Inc. All rights reserved.)

In the last decade, the number of haploidentical stem cell transplantation has increased because of the widespread use of T-cell-replete platforms developed worldwide. Acute myeloid leukemia (AML) is the main indication to perform allogeneic stem cell transplantation. Here, we reviewed the clinical results obtained using T-cell-replete platforms in different clinical situations such as first or further complete remission, refractory disease, and in the elderly population. Overall, the toxic profile of T-cell-replete haploidentical transplantation is similar to transplantation from other donors, with positive aspects such as a reduced incidence of chronic graft-versus-host disease. Leukemia-free survival and overall survival are also similar. In conclusion, T-cell-replete haploidentical transplantation represents a new frontier in the treatment landscape of AML, lessening problems linked to donor search and ensuring that a donor can be found for all patients in a timely manner., (Copyright © 2018 ISEH – Society for Hematology and Stem Cells. Published by Elsevier Inc. All rights reserved.)

We analyzed the main modalities and clinical outcomes of the early discharge outpatient model in autologous stem cell transplantation (EDOM-ASCT) for multiple myeloma in Italy. EDOM-ASCT was employed in 382 patients, for a total of 522 procedures, between 1998 and 2012. Our study showed high homogeneity among centers in terms of inclusion criteria, supportive care, and in hospital readmission criteria. Overall, readmissions during the aplastic phase occurred in 98 of 522 transplantations (18.8%). The major extrahematological complication was neutropenic fever in 161 cases (30.8%), which required readmission in 76 cases. The incidence of severe World Health Organization grade 3 to 4 mucositis was 9.6%. By univariate analysis, fever, mucositis, altered renal function at diagnosis, second transplantation, and transplantation performed late in the course of the disease were significantly correlated with readmission, whereas fever, mucositis, altered renal function, and timing of transplantation remained the only independent predictors by multivariate analysis. Overall, transplantation-related mortality was 1.0%. No center effect was observed in this study (P = .36). The safety and low rate of readmission of the EDOM-ASCT in myeloma trial suggest that this strategy could be extended to other transplantation centers if a stringent patient selection and appropriate management are applied., (Copyright © 2014 American Society for Blood and Marrow Transplantation. Published by Elsevier Inc. All rights reserved.)

Myeloma relapse is the main cause of death after allogeneic stem cell transplantation. The aim of our observational study was to evaluate the anti-myeloma effect of lenalidomide followed by donor-lymphocyte infusion (DLI) as post-transplantation adoptive immunotherapy. Twelve patients with refractory myeloma were analyzed. The median age at transplantation was 56 years (range, 46-64 years). All patients received reduced-intensity conditioning. Patients were included if progressive or residual disease was observed at day +100 and if no signs of graft-vs-host disease were evident. DLIs were administered after two cycles of lenalidomide. Median dose of lenalidomide was 15 mg (range, 10-25 mg). Patients received a median of six cycles (range, 1-10 cycles). Nine patients (60%) received an escalating dose of DLI. The 1 and 2-year probability of progression-free survival was 75% and 50%, and overall survival was 83% and 69%, respectively. Median overall survival was not reached and median progression-free survival was 23 months. Lenalidomide is well tolerated after allogeneic stem cell transplantation; the combination with DLI did not cause a higher risk of graft-vs-host disease; an immunological synergistic effect was probably present with this strategy. This combination should be evaluated further in a larger cohort of patients., (Copyright © 2012 ISEH - Society for Hematology and Stem Cells. Published by Elsevier Inc. All rights reserved.)

Over the past 15 years, the use of reduced-intensity/nonmyeloablative conditioning regimens before allogeneic hematopoietic stem cell transplantation has been increasing. Despite major disparities in the level of myeloablation, intensity of immunosuppression (including great diversity of in vivo T-cell depletion), and postgraft immunomodulation, the different approaches have contributed jointly to a modification of the stage of allogeneic stem cell transplantation: transplantation-related procedure mortality has been decreased dramatically, allowing allogeneic immunotherapy to be used in previously excluded populations, including elderly patients, young but clinically unsuitable patients, patients with lymphoid malignancies or solid tumors, and patients without an HLA-identical related or unrelated donor. Together, these diverse regimens have provided one of the biggest breakthroughs since the birth of allogeneic BM transplantation. However, consensus on how to reach the optimal goal of minimal transplantation-related mortality with maximum graft-versus-tumor effect is far from being reached, and further studies are needed to define optimal conditioning and immunomodulatory regimens that can be integrated to reach this goal. These developments, which will most likely vary according to different clinical situations, have to be compared continuously with advances achieved in traditional allogeneic transplantation and nontransplantation treatments. However, the lack of prospective comparative trials is and will continue to make this task challenging.

Nearly 80% of patients with Hodgkin's disease (HD) are cured with chemotherapy with or without radiotherapy. However, in patients with primary refractory or relapsed disease, high-dose therapy (HDT) and autologous or peripheral-blood stem-cell transplantation (ASCT or PBSCT) represents the best curative option. Several prognostic factors to identify patients at high risk for relapse or progression have been analyzed. However, in almost all analyzed series, disease status before high-dose chemotherapy with PBSC support remains the most important factor predicting the outcome of these patients. Nonetheless, the benefit of cytoreduction before HDT has yet to be fully determined and efforts to identify the best active regimen, combining therapeutic activity and CD34+ stem-cell mobilizing potential, represent a challenging issue for these patients. Furthermore new approaches like myeloablative and non-myeloablative allogeneic transplants have been assessed to improve long-term in such patients. In this review we analyzed the results of the most important salvage chemotherapy combinations as well as allogeneic transplantations to clarify the optimal treatment options for patients with resistant/relapsing HD.

Refractory acute myeloid leukaemia is very difficult to treat and represents an unmet clinical need. In recent years, new drugs and combinations of drugs have been tested in this category, with encouraging results. However, all treated patients relapsed and died from the disease. The only curative option is allogeneic transplantation through a graft from a healthy donor immune system. Using myeloablative conditioning regimens, the median overall survival regimens is 19%. Several so-called sequential induction chemotherapies followed by allogeneic transplantation conditioned by reduced intensity regimens have been developed, improving the overall survival to 25–57%. In the allogeneic transplantation field, continuous improvements in practices, particularly regarding graft versus host disease prevention, infection prevention, and treatment, have allowed us to observe improvements in survival rates. This is true mainly for patients in complete remission before transplantation and less so for refractory patients. However, full myeloablative regimens are toxic and carry a high risk of treatment-related mortality. In this review, we describe the results obtained with the different modalities used in more recent retrospective and prospective studies. Based on these findings, we speculate how allogeneic stem cell transplantation could be modified to maximise its therapeutic effect on refractory acute myeloid leukaemia. [ABSTRACT FROM AUTHOR]

Allogeneic stem cell transplantation remains the only therapy for congenital, severe haemoglobinopathies that is able to reverse the pathological phenotype. In the severe form of thalassemia, regular transfusions are needed early in life. This population of patients could benefit from allo-SCT. However, the great efficacy of transplantation must be counterbalanced by the mortality and morbidity related to the procedure. In this short review, we reviewed the most recent data in the field of transplantation in transfusion-dependent thalassemia (TDT), highlighting the factors that have a major impact on outcomes. [ABSTRACT FROM AUTHOR]

Even with high-dose post-transplant cyclophosphamide (PT-Cy) which was initially introduced for graft-versus-host disease (GvHD) prevention in the setting of HLA-haploidentical transplantation, both acute and chronic GvHDs remain a major clinical challenge. Despite improvements in the understanding of the pathogenesis of both acute and chronic GvHDs, reliable biomarkers that predict their onset have yet to be identified. We recently studied the potential correlation between extracellular vesicles (EVs) and the onset of acute (a)GvHD in transplant recipients from related and unrelated donors. In the present study, we further investigated the role of the expression profile of membrane proteins and their microRNA (miRNA) cargo (miRNA100, miRNA155, and miRNA194) in predicting the onset of aGvHD in haploidentical transplant recipients with PT-Cy. Thirty-two consecutive patients were included. We evaluated the expression profile of EVs, by flow cytometry, and their miRNA cargo, by real-time PCR, at baseline, prior, and at different time points following transplant. Using logistic regression and Cox proportional hazard models, a significant association between expression profiles of antigens such as CD146, CD31, CD140a, CD120a, CD26, CD144, and CD30 on EVs, and their miRNA cargo with the onset of aGvHD was observed. Moreover, we also investigated a potential correlation between EV expression profile and cargo with plasma biomarkers (e.g., ST2, sTNFR1, and REG3a) that had been associated with aGVHD previously. This analysis showed that the combination of CD146, sTNFR1, and miR100 or miR194 strongly correlated with the onset of aGvHD (AUROC >0.975). A large prospective multicenter study is currently in progress to validate our findings. [ABSTRACT FROM AUTHOR]

Rituximab (R) is increasingly incorporated in reduced intensity conditioning (RIC) regimens for allogeneic hematopoietic cell transplantation (alloHCT) in patients with B-cell malignancies, not only to improve disease control, but also to prevent graft-versus-host disease (GVHD). There are no randomized prospective data to validate this practice, although single center data and the CIBMTR analysis have shown promising results. We aimed at validation of these findings in a large registry study. We conducted a retrospective analysis using the EBMT registry of 3,803 adult patients with B-cell malignancies undergoing alloHCT (2001–2013) with either rituximab (R-RIC-9%) or non-rituximab (RIC-91%) reduced intensity regimens respectively. Median age and median follow up were 55 years (range 19.1–77.3) and 43.2 months (range 0.3–179.8), respectively. There was no difference in transplant outcomes (R-RIC vs RIC), including 1-year overall survival (69.9% vs 70.7%), 1-year disease-free survival (64.4% vs 62.2%), 1-year non-relapse mortality (21% vs 22%), and day-100 incidence of acute GVHD 2-4° (12% vs 12%). In summary, we found that addition of rituximab in RIC regimens for B-cell malignancies had no significant impact on major transplant outcome variables. Of note, data on chronic GVHD was not available, limiting the conclusions that can be drawn from the present study. [ABSTRACT FROM AUTHOR]

• Nonmyeloablative haploidentical stem cell transplantation for advanced lymphomas is highly feasible with low incidence of nonrelapse mortality. • It provides a strong graft-versus-lymphoma effect for both Hodgkin and non-Hodgkin lymphoma, with low incidence of relapse when performed in partial or complete remission. Allogeneic hematopoietic stem cell transplantation (allo-SCT) is a valid option in patients with refractory lymphomas. HLA haploidentical stem cell transplantation (haplo-SCT) expanded the accessibility to allogeneic hematopoietic cell transplantation. The aims of study were to retrospectively assess the toxicity and efficacy of haplo-SCT using nonmyeloablative conditioning in patients with advanced lymphoma. In total, 147 patients with advanced lymphoma at 2 partner institutions were included. Patients received a uniform nonmyeloablative conditioning regimen and graft-versus-host disease (GVHD) prophylaxis. The primary endpoints were progression-free survival (PFS), overall survival (OS), GVHD, nonrelapse mortality, and GVHD, relapse-free survival (GRFS). Median follow-up was 39 months (range, 6 to 114 months). The median age was 46 years (range, 19 to 71 years). Sixty-five percent of patients were in complete remission (CR) at transplantation. Cumulative incidence of grade II to IV acute GVHD was 30% (95% confidence interval [Cl], 23% to 38%). Two-year cumulative incidence of all grades of chronic GVHD was 13% (95% CI, 8% to 20%). Two-year cumulative incidence of disease relapse was 19% (95% CI, 14% to 27%), with a higher incidence in patients not being in CR at allo-HCT (CR versus not CR: 12% versus 33%, P =.006). Two-year PFS, OS, and GRFS were 66% (95% CI, 59-75), 73% (95% CI, 66-81), and 56% (95% CI, 48-65), respectively. Haplo-SCT with post-transplantation cyclophosphamide may be considered a valid option for patients with aggressive lymphoma and deserves further evaluation. [ABSTRACT FROM AUTHOR]

Background: The use of post-transplant cyclophosphamide (PTCy) is highly effective in preventing graft-versus-host disease (GVHD) in the haploidentical (Haplo) transplant setting and is being increasingly used in matched sibling (MSD) and matched unrelated (MUD) transplants. There is no information on the impact of donor types using homogeneous prophylaxis with PTCy. Methods: We retrospectively compared outcomes of adult patients with acute myeloid leukemia (AML) in first complete remission (CR1) who received a first allogeneic stem cell transplantation (SCT) with PTCy as GVHD prophylaxis from MSD (n = 215), MUD (n = 235), and Haplo (n = 789) donors registered in the EBMT database between 2010 and 2017. Results: The median follow-up was 2 years. Haplo-SCT carried a significantly increased risk of acute grade II–IV GVHD (HR 1.6; 95% CI 1.1–2.4) and NRM (HR 2.6; 95% CI 1.5–4.5) but a lower risk of relapse (HR 0.7; 95% CI 0.5–0.9) that translated to no differences in LFS (HR 1.1; 95% CI 0.8–1.4) or GVHD/relapse-free survival (HR 1; 95% CI 0.8–1.3). Interestingly, the use of peripheral blood was associated with an increased risk of acute (HR 1.9; 95% CI 1.4–2.6) and chronic GVHD (HR 1.7; 95% CI 1.2–2.4) but a lower risk of relapse (HR 0.7; 95% CI 0.5–0.9). Conclusions: The use of PTCy in patients with AML in CR1 receiving SCT from MSD, MUD, and Haplo is safe and effective. Haplo-SCT had increased risk of acute GVHD and NRM and lower relapse incidence but no significant difference in survival. [ABSTRACT FROM AUTHOR]

Summary: Haploidentical stem cell transplantation (haploSCT) is becoming a major transplant modality for lymphoma. To assess the effects of donor characteristics, stem cell source and conditioning on outcomes, we identified 474 adults with Hodgkin (HL; 240), peripheral T‐cell (PTCL; 88), diffuse large B‐cell (77), mantle cell (40) or follicular lymphoma (FL; 29), who received haploSCT with post‐transplant cyclophosphamide. Median follow‐up of alive patients was 32 months. On multivariate analysis, acute graft‐versus‐host disease (GVHD) grade 2–4 was lower with offspring donors or bone marrow cells, whereas extensive chronic GVHD was higher in partial response at haploSCT or when using sisters, haploidentical donors beyond first degree, or female donors in male patients. Progression‐free survival (PFS) was better for FL, HL and PTCL, whereas overall survival (OS) was better for HL and PTCL. Complete remission at haploSCT improved PFS and OS whereas these were negatively affected by cytomegalovirus donor positive/recipient positive status. No other donor characteristics (age, gender, human leucocyte antigen mismatch, ABO incompatibility) affected PFS or OS except use of haploidentical donors beyond first degree, which negatively affected OS. PFS and OS are mostly influenced by disease status and lymphoma subtype, supporting the use of any first degree haploidentical family member as a donor. [ABSTRACT FROM AUTHOR]

Cytokine release syndrome (CRS) represents a life‐threatening side effect after haploidentical stem cell transplantation (Haplo‐SCT) with posttransplant cyclophosphamide (PT‐Cy). Factors predictive of CRS development is still a matter of debate. We retrospectively analyzed 102 consecutive patients receiving a bone marrow (BM) (n = 42) or peripheral blood stem cells (PBSC) (n = 60) Haplo‐SCT with PT‐Cy. The two cohorts were similar in main patients' characteristics besides disease type (P =.02). Cumulative incidence of grades 1, 2, and ≥3 CRS was 80%, 52%, and 15% at a median of 2, 4, and 7 days, respectively. Moderate/High‐grade fever (39°‐41°), grade 1 and grade ≥3 CRS occurred more frequently after PBSC relative to BM grafts (68% vs 33%, P =.0005; 87% vs 71%, P =.009; 20% vs 7%, P =.07). Only patients experiencing grade ≥3 CRS had a worse outcome in terms of 1‐year overall survival (OS) and nonrelapse mortality (NRM): 39% vs 80% (P =.002) and 40% vs 8% (P =.005), respectively. By univariate analysis the only factors associated with the increased risk of ≥3 CRS were pretransplant disease status (8% for complete remission, 11% for partial remission, and 38% for active disease, P =.002), HLA‐DRB1 mismatching (57% vs 14%, P =.007), and PBSC graft (P =.07). By multivariable analysis, only pretransplant disease status (hazard ratio, HR: 6.84, P =.005) and HLA‐DRB1 mismatching (HR: 17.19, P =.003) remained independent predictors of grade ≥3 CRS. Only grade ≥3 CRS is clinically relevant for the final outcome of patients receiving Haplo‐SCT with PT‐Cy, is more frequent after a PBSC graft and is associated with pretransplant active disease and HLA‐DRB1 mismatching. [ABSTRACT FROM AUTHOR]

Transplantation from haploidentical donors is widely used, with progressive reduction of cord blood (CB) as alternative donor. The paper by Matsuda and colleagues, the largest analysing the outcome in non‐remission acute myeloid leukaemia (AML) transplanted with haploidentical donor or CB, suggests that CB is still a viable option when considering allogeneic transplantation for advanced AML. Commentary on: Matsuda et al. Comparison of transplant outcomes between haploidentical transplantation and single cord blood transplantation in non‐remission acute myeloid leukaemia: A nationwide retrospective study. Br J Haematol. 2023;201:106–113. [ABSTRACT FROM AUTHOR]

The article focuses on the survival and relapse rate associated with immunotherapy donor lymphocyte infusion (DLI) which is used for allogeneic haematopoietic stem cell transplantation (Allo-HSCT). It talks about the Allo-HSCT being used for treatment in patients with haematological malignancies. It tells about the non-relapse mortality (NRM) rate being low for Allo-HSCT.

Objectives: T‐cell–replete haploidentical stem cell transplantation (Haplo‐SCT) with post‐transplant cyclophosphamide (PT‐Cy) is at high risk of invasive fungal infections (IFI), and anti‐mold–active drug is required for primary antifungal prophylaxis (PAP) according to international guidelines. No data are available on the efficacy of caspofungin as PAP in this setting. Methods: Here, we report our retrospective experience with 103 consecutive patients treated with caspofungin as PAP after Haplo‐SCT. Caspofungin was administered only during the pre‐engraftment phase. Results: Hundred‐day cumulative incidence of proven‐probable IFI (PP‐IFI) was 8.7% and median day of onset was 19 post‐SCT. No patient died of PP‐IFI, and overall survival (OS) and non‐relapse mortality (NRM) hazard ratio (HR) for patients experiencing IFI were 1.02 (P = 0.9) and 0.7 (P = 0.7), respectively. Three‐year overall survival (OS) and 1‐year non‐relapse mortality (NRM) were 55% and 19%, respectively. By univariate analysis, duration of neutropenic phase and partial remission pre‐transplant disease status were associated with increased incidence of IFI, but were not confirmed by multivariate analysis. Conclusion: In summary, PAP with caspofungin is an effective strategy for preventing IFI in the context of Haplo‐SCT with PT‐Cy. Further efforts are required in order to identify more potent strategies able to avoid the occurrence of breakthrough infections. [ABSTRACT FROM AUTHOR]

Background: The treatment of patients with Hodgkin lymphoma (HL) who develop disease progression after undergoing allogeneic stem cell transplantation (allo-SCT) remains challenging.Methods: The authors assessed outcomes in 184 adult patients with HL who developed disease recurrence or progression after a matched related or unrelated allo-SCT at European Society for Blood and Marrow Transplantation-participating centers between 2010 and 2014.Results: Eighty patients who received brentuximab vedotin (BV) salvage therapy were compared with 104 patients who did not. Patients in the BV group were younger (median age of 30 years vs 34 years) and were more likely to receive pretransplant BV (65% vs 46%) or posttransplant donor lymphocyte infusion (66% vs 33%). The 2 groups otherwise were comparable. Patients in the BV group received a median of 6 doses of posttransplant BV, resulting in a complete remission rate of 29%, a partial response rate of 45%, and a stable disease rate of 26%. Response to BV after allo-SCT did not appear to be affected by receipt of pretransplant BV. Despite a longer median follow-up for surviving patients in the BV group (33 months vs 23 months; P<.001), approximately 34% of the original BV cohort were alive and in CR at the time of last follow-up versus 18% in the group that did not receive BV (P=.003). The use of BV before donor lymphocyte infusion was found to be associated with the highest probability of being alive and in CR (40%) at the time of last follow-up. Salvage BV appeared to have no effect on chronic graft-versus-host disease or 1-year overall survival from the time of disease recurrence after allo-SCT (76% vs 67%).Conclusions: BV is a safe and effective salvage therapy for patients with HL who develop disease recurrence or progression after undergoing allo-SCT, even after prior exposure to BV. [ABSTRACT FROM AUTHOR]

Summary: Brentuximab vedotin (BV) is an anti‐CD30 antibody‐drug conjugate. Preliminary data suggest that BV might improve outcomes after allogeneic stem cell transplantation (SCT) for Hodgkin lymphoma (HL) when used as pre‐transplant salvage therapy. Between 2010 and 2014, 428 adult patients underwent an allogeneic SCT for classical HL at participating centres of the European Society for Blood and Marrow Transplantation. We compared the outcomes of 210 patients who received BV prior to allogeneic SCT with that of 218 patients who did not receive BV. The median follow‐up for survivors was 41 months. Patients in the BV group were more heavily pre‐treated (median pre‐allograft treatment lines: 4 vs. 3). The two groups were comparable in terms of disease status, performance status, comorbidities, prior autologous SCT, type of donor, conditioning and in vivo T cell depletion. In multivariate analysis, pre‐allograft BV had no impact on acute graft‐versus‐host disease (GVHD), non‐relapse mortality, cumulative incidence of relapse, progression‐free survival or overall survival (OS), but significantly reduced the risk of chronic GVHD (hazard ratio = 0·64; 95% confidence interval = 0·45–0·92; P < 0·02). Older age, poor performance status, use of pre‐transplant radiotherapy and active disease at SCT adversely affected OS. Patients allografted for HL after prior exposure to BV do not have a superior outcome after allogeneic SCT except for a lower risk of chronic GVHD. However, BV may improve the outlook of allogeneic SCT by helping otherwise refractory patients to achieve a more favourable disease status, facilitating allotransplant success. [ABSTRACT FROM AUTHOR]

The monitoring of Human Herpesvirus 6 (HHV-6) after allogeneic stem cell transplantation has proven to be useful in preventing life-threatening complications; however, the pathogenic role of HHV-6 after autologous transplantation is not well-characterized, although viral reactivation might be responsible for significant complications even after this type of transplant. Here we report, for the first time to our knowledge, the case of a patient with chromosomally integrated HHV-6 (ciHHV-6), presenting with high titers of HHV-6 DNA copies after autologous transplantation, mimicking HHV-6 reactivation. The presence of viral DNA in the follicle bulb confirmed the ciHHV-6 and allowed for the discontinuation of the antiviral treatment. Due to the increasing awareness of HHV-6 potential pathogenicity and the fact that ciHHV-6 is expected in 1-2% of the population, such a case might be helpful in recognizing ci HHV-6, thus avoiding unnecessary and potentially toxic antiviral therapy once the viral genomic integration is confirmed. [ABSTRACT FROM AUTHOR]

The optimal intensity of myeloablation associated with a reduced-toxicity conditioning (RTC) regimen in order to decrease the relapse rate without increasing non-relapse mortality (NRM), is not well established yet. This retrospective analysis was done on 30 patients with hematological malignancies. The aim was to assess the safety of a RTC regimen based on the busulfan at a dose of 100 mg/m2/d intravenously for 4 d, fludarabine at a dose of 30 mg/m2/d for 5 d, and anti-thymoglobulins at a dose of 2.5 mg/kg/d for 2 d. The cumulative incidences of grade 2–4 acute graft-versus-host disease (GVHD) and all grades chronic GVHD were 37% and 42%, respectively. Median 1-year overall survival and disease-free survival were 66% and 50%, respectively. At 1 year, the cumulative incidence of relapse/disease progression was 33%. NRM was 3% and 17% at day 100 and 1 year, respectively. This RTC conditioning regimen can lead to a long-term disease control. Moreover, it appears to be safe with a low NRM rate among high-risk patients. [ABSTRACT FROM AUTHOR]

Allogeneic stem cell transplantation (allo-SCT) is considered the cornerstone in the treatment of several malignant and not malignant hematological diseases. However, relapse of hematological disease after allo-SCT is considered the most challenging point in the field. The risk can be reduced through optimal patients, donor and disease selection before allo-SCT, but harnessing donor immune system is an appealing way to treat or avoid disease relapse. Donor lymphocyte infusion (DLI) is a simple and effective therapy after allo-SCT. In this paper, the efficacy of DLI will be analyzed in different hematological diseases, focusing also on their therapeutic or pre-emptive use. [ABSTRACT FROM AUTHOR]

Brentuximab vedotin (BV) is a chimeric anti-CD30 conjugated to monomethyl auristatin E (MMAE) is an active drugs against (Hodgkin Lymphoma) HL cells. BV can be used in case of relapse or progressing after high dose chemotherapy; in patients refractory to conventional chemotherapy; as consolidation treatment after high dose chemotherapy in high risk patients; in patients relapsing after allogeneic stem cell transplantation (allo-SCT). In all these situations, BV is effective and well tolerated. In this paper we summarized the results reported in the literature. [ABSTRACT FROM AUTHOR]

Background. Brentuximab vedotin (BV) has demonstrated an extraordinary efficacy in heavily pretreated classical Hodgkin lymphoma (cHL) patients, targeting CD30-positive cells; however, limited data have been reported on the efficacy of BV in cHL patients failing allogeneic stem cell transplantation (allo-SCT).The aim of this studywasto retrospectively evaluate the efficacy and safety of BV in a multicenter setting of cHL relapsing or progressing after allo-SCT. Methods. Sixteen BV-na¨ıve patients with recurrent cHL after allo-SCT were included in a compassionate use program and treated with intravenous BV at the dose of 1.8 mg/kg of body weight every 3 weeks for a maximum of 16 cycles. Results. The objective response rate was 69%. Five patients (31%) had complete remission, and 6 (37%) had partial remission. Stable disease was observed in 4 patients (25%), and progressive disease was observed in 1 (6%). After median follow-up of 26 months (range: 5-30 months), median progression-free survival (PFS), overall survival (OS), and duration of response were 7, 25, and 5 months, respectively. The 2-year PFS and OS were 20% and 61%, respectively. Grade 3-4 hematological adverse events included anemia (15%), thrombocytopenia (12%), and neutropenia (18%). Grade 3 peripheral sensory neuropathy occurred in 2 patients (12%). Conclusion. BV therapy is an effective and safe approach for achieving transient disease control in cHL patients with failed allo-SCT. To improve disease control, future studies should explore the combination of BV with targeted agents. [ABSTRACT FROM AUTHOR]

Abstract: 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. [Copyright &y& Elsevier]

BACKGROUND: The optimal combination of fludarabine, busulfan, and antithymocyte globulin (ATG) for reduced-intensity conditioning (RIC) transplantation has not been established. ATG plays a pivotal role in the prevention of graft-versus-host disease (GvHD), but it is associated with a higher relapse rate and an elevated incidence of infections when high doses are used. METHODS: The authors retrospectively compared 2 different doses of ATG combined with fludarabine and busulfan in 229 adult patients who underwent transplantation at their institution. ATG was administered over 1 day (FBA1) or over 2 days (FBA2) at a daily dose of 2.5 mg/kg. RESULTS: There were 124 patients in the FBA2 cohort and 105 patients in the FBA2 cohorts. Patients in the FBA2 cohort were older and more frequently underwent transplantation from an unrelated donor; 93% of patients in the FBA2 cohort received intravenous busulfan versus only 5% in the FBA1 cohort. The incidence of grade 2 through 4 acute GvHD was 23% in the FBA2 cohort versus 42% in the FBA1 cohort ( P = .002); the incidence of grade 3 through 4 acute GvHD was 10% versus 23%, respectively ( P = .006); and the incidence of chronic GvHD was 35% versus 69%, respectively ( P < .0001). The 2-year rates of overall survival, nonrelapse mortality, and relapse/progression for the FBA1 and FBA2 cohorts were 65% versus 67%, respectively ( P = .99), 20% versus 19%, respectively ( P = .61), and 30% versus 19%, respectively ( P = .09). The results were confirmed in multivariate analysis. CONCLUSIONS: The use of ATG at a dose of 5 mg/kg was correlated significantly with reduced incidence and severity of GvHD without impairing disease control. Taken together, the current results suggest that this conditioning represents a step forward in the optimization of RIC. Cancer 2013. © 2012 American Cancer Society. [ABSTRACT FROM AUTHOR]

BACKGROUND: The optimal intensity of reduced-intensity conditioning (RIC) before allogeneic hematopoietic stem cell transplantation (allo-HSCT) remains uncertain. METHODS: In this centrally randomized phase 2 study, the authors compared 2 different strategies of RIC. In total, 139 patients (median age, 54 years; range, 21-65 years) with hematologic malignancies underwent allo-HSCT from a human leukocyte antigen-identical sibling after conditioning combining fludarabine with either busulfan and rabbit antithymocyte-globulin (BU-rATG) (n = 69) or total body irradiation (TBI) (n = 70). Postgraft immunosuppression consisted of cyclosporin A in all patients with the addition of mycophenolate-mophetil after TBI. RESULTS: The median follow-up was 54 months (range, 26-88 months). One-year overall survival rate was identical in both groups. Four patients experienced graft-failure after TBI. The incidence of grade 2 through 4 acute graft-versus-host-disease was greater after BU-rATG than after TBI (47% vs 27%; P = .01), whereas no difference was observed with chronic graft-versus-host-disease. The BU-rATG group had a higher objective response rate (65% vs 46%; P = .05) and a lower relapse rate (27% vs 54%; P < .01). However, the nonrelapse mortality rate was higher after BU-rATG than after TBI (38% vs 22%; P = .027). At 5 years, the overall and progression-free survival rates were 41% and 29%, respectively, and did not differ statistically between groups. A detrimental effect on some parameters of quality of life was more pronounced after BU-rATG, but recovery was identical in both groups. The mean total cost per patient, including the cost to treat disease progression post-transplantation, did not differ statistically between groups. CONCLUSIONS: Five years after transplantation, the BU-rATG regimen was associated with greater disease control. However, because of the higher nonrelapse mortality rate, this did not translate into better overall or progression-free survival. Cancer 2013. © 2012 American Cancer Society. [ABSTRACT FROM AUTHOR]

The article discusses research which investigated poor autologous mobilization incidence in multiple myeloma (MM) and lymphoma patients that received reduced-intensity conditioning (RIC) allogeneic hematopoietic stem cell transplantation (alloSCT). Topics explored include the use of antithymocyte globulin conditioning in alloSCT, the classification of patients that are deemed as either good or poor mobilizers, and the adverse events recorded following alloSCT.

Invasive aspergillosis (IA) is a major cause of morbidity in patients with hematological malignancies, and a major impediment to the success of allogeneic stem cell transplant (allo-SCT). The aim of this single-center retrospective study was to determine the impact of pre-transplant IA on the outcome of allo-SCT after reduced-intensity conditioning (RIC). Twenty-eight cases of proven or probable IA were diagnosed prior to RIC allo-SCT at the Paoli-Calmettes Institute Cancer Center between January 2000 and January 2008. These cases were identified among 360 patients undergoing allo-SCT. IA was defined according to EORTC criteria. Patients had predominantly (82%) acute myeloid leukemia, were diagnosed with IA at a median of 8 months (range, 1–16) pre-transplant, and received antifungal therapy for a median of 5 months (range, 1–13). IA therapy included: voriconazole (71%); single-agent itraconazole (14%); and a combination of agents (14%). Secondary prophylaxis against aspergillosis was maintained during conditioning and post-transplant in 89% of patients. After transplant, only three patients (11%) had reactivation of their IA and one patient developed disseminated fusariosis. The latter four patients experienced severe acute GVHD treated with high-dose corticosteroids. None of these patients died of IA. Eighteen patients (64%) are still alive, with a median follow-up of 23.5 months (range, 12.6–48.5). Overall survival at 2 years was 59% (95% CI, 43–83%). These data suggest that patients with adequately controlled IA can tolerate RIC allo-SCT without significant post-transplant complications. [ABSTRACT FROM AUTHOR]

Abstract: The aim of this study was to assess the role of allogeneic hematopoietic stem cell transplantation (HSCT) in patients with poor-risk Hodgkin''s disease (HD) compared to chemotherapy. A donor was identified in 26 patients (14 HLA identical siblings and 10 alternative donors), and 24 received a transplant (Allo group). Twenty patients without a donor received different chemotherapy regimens and radiotherapy (CHEMO group). After a median follow-up of 28 months (range: 1-110), the 2-year overall survival (OS) was 71% in the ALLO group compared to 50% in the CHEMO group (P = .031). In the Allo group, the 2-year progression-free survival (PFS) was 47%. The 1-year nonrelapse mortality (NRM) in the ALLO group was 8% versus 0% in the CHEMO group. This study, suggests that allogeneic transplantation may prolong the survival in patients with a poor-risk HD. [Copyright &y& Elsevier]

Our goal was to optimize use of granulocyte colony-stimulating factor (G-CSF) after high-dose chemotherapy and autologous peripheral blood stem-cell transplantation in lymphoma patients, limiting G-CSF administration to patients infusing a suboptimal CD34+ cell number. Of 124 consecutive patients with histologically proven Hodgkin's and non-Hodgkin's lymphoma from January 2001 to June 2004, 60 patients (group 1) given ≥5 × 106/kg CD34+ cells received no G-CSF; 64 patients (group 2) given ≤5 × 106/kg CD34+ cells received G-CSF from day +5 after stem-cell reinfusion. The median times to reach 0.5 × 109/L and 1.0 × 109/L neutrophils were, respectively, 3 and 4 d shorter in G-CSF group and this difference was statistically significant ( P = 0.0014; P = 0.0001). In terms of antibiotic and antimycotic requirements, gastrointestinal toxicity, days of hospitalization, and transfusion requirements, no differences were demonstrated between the two groups. No statistically significant difference was demonstrated for the total number of febrile episodes (52 for group 1; 53 for group 2; P = 0.623) and the median number of febrile days (2 d for both groups). Myeloid reconstitution values for both groups agree with published results for autotransplanted patients treated with G-CSF from 7 to 14 d. Also, major clinical events, antibiotic, antimycotic, and transfusion requirements, and hospital stay were similar to published findings. Our data suggest that G-CSF administration can be safely optimized, used only for patients infused with a suboptimal CD34+ cell dose. [ABSTRACT FROM AUTHOR]

Background: Allogeneic stem cell transplantation from haploidentical donor using an unmanipulated graft and post-transplantation cyclophosphamide (PT-Cy) is growing. Haploidentical transplantation with PT-Cy showed a major activity in Hodgkin lymphoma (HL), reducing the relapse incidence. The most important predictive factor of survival and toxicity was disease status before transplantation, which was better in patients with well controlled disease.Methods: We included 198 HL in complete (CR) or partial remission (PR) before transplantation. Sixty-five patients were transplanted from haploidentical donor and 133 from a HLA identical donor (both sibling and unrelated donors). Survival analysis was defined according to the EBMT criteria. Survival curves were generated by using Kaplan-Meier method and differences between groups were compared by the log rank test or by the log rank test for trend when appropriated.Results: The PFS, OS, and RI were significantly better in patients in CR compared to PR (55% vs 29% p = 0.001, 74% vs 55% p = 0.03, 27% vs 55% p <  0.001, respectively). The 2-year PFS was significantly better for HAPLO than HLA-id (63% vs 37%, p = 0.03), without difference in OS. The 1-year NRM was not different. The 2-year relapse incidence (RI) was lower in the HAPLO group (24% vs 44%, p = 0.008). Patients in CR receiving haplo HSCT showed higher 2-year PFS and lower 2-year RI than those allografted with HLA-id donor (75% vs 47%, p <  0.001 and 11% vs 34%, p < 0.001, respectively). In multivariate analysis, donor type and disease status before transplantation were independent predictors of PFS as well as they predict the risk of relapse. Disease status at transplantation and age were independently associated to OS.Conclusions: Nonetheless this is a retrospective study, limiting the wide applicability of results, data from this analysis suggest that HLA mismatch can induce a strong graft versus lymphoma effect leading to an enhanced PFS. [ABSTRACT FROM AUTHOR]

T-cell replete Haploidentical stem cell transplantation (Haplo-SCT) with Post-transplant cyclophosphamide (PT-Cy) is an emerging therapeutic option for patients with advanced relapsed or refractory lymphoma. The feasibility of this platform is supported by several retrospective studies showing a toxicity profile that is improved relative to umbilical cord blood and mismatched unrelated donor (UD) transplant and comparable to matched unrelated donor transplant. In particular, cumulative incidence of chronic graft-versus-host disease (GVHD) is reduced after Haplo-SCT relative to UD and matched related donor (MRD) transplant thanks to PT-Cy employed as GVHD prophylaxis. This achievement, together with a similar incidence of acute GVHD and disease relapse, results in a promising advantage of Haplo-SCT in terms of relapse-free/GVHD free survival. Unmet needs of the Haplo-SCT platform are represented by the persistence of a not negligible rate of non-relapse mortality, especially due to infections and disease relapse. Future efforts are warranted in order to reduce life-threatening infections and to employ Halo-SCT with PT-Cy as a platform to build new immunotherapeutic strategies. [ABSTRACT FROM AUTHOR]

The article presents a case study of a 61-year old woman who was suffering from relapsed mutliple myeloma. She received an allogeneic hematopoietic stem cell transplant from a human leukocyte antigen (HLA) unrelated donor. Both the patient and the donor were postive for Epstein-Barr virus-related meningoencephalitis. The patient then received intravenous rituximab monotherapy. The treatment was found to be successful with the involvement of central nervous system and without MRI lesions.

Although the median age of patients with non Hodgkin's lymphoma (NHL) is about 65 years, and is one of the most important prognostic factors in NHL 1,2 high-dose therapy followed by autologous stem cell transplantation have traditionally been restricted to younger patients. This practice is based on the premise that older patients may not tolerate the intensity of this treatment, may by unable to provide an adequate stem cell graft, or may have an overall poorer prognosis. We have analyzed our experience with HDT supported by PBSCT in 12 elderly patients with NHL treated from August 1998 to July 2001, and compared the outcome and toxicity of the procedure with 26 younger matched NHL patients who were matched on the basis of disease status at transplant, performance status, IPI score, number of pre-transplant chemotherapy regimen and conditioning regimens.

• There is no standard schedule for post-transplantation cyclophosphamide (PTCY) and associated immunosuppressors in recipients of haploidentical transplantation. • Early introduction of cyclosporine A and mycophenolate mofetil with PTCY on days +3 and +5 results in better refined graft-versus-host disease-free, relapse-free survival and leukemia-free survival. The timing of immunosuppressive therapy used in combination with post-transplantation cyclophosphamide (PTCY) in haploidentical hematopoietic stem cell transplant (haplo-HSCT) is not standardized. We evaluated the schedules of immunosuppression therapy after haplo-HSCT in 509 patients with acute leukemia receiving PTCY on days +3 and +4 along with tacrolimus (group 1; n = 215), with cyclosporine A (CSA) and mycophenolate mofetil (MMF) from day +5 (group 2; n = 170), or CSA + MMF from day 0 or 1 with PTCY on days +3 and +5 (group 3; n = 124). Compared with the other 2 groups, patients in group 3 were younger (median age, 46 years; P =.02) and more often received bone marrow (77%; P <.01) and a regimen containing thiotepa, fludarabine, and busulfan (84%; P <.01). At 2 years, overall survival was 44% was in group 1, 48% in group 2, and 59% in group 3 (P =.15); leukemia-free survival (LFS) was 43%, 46%, and 53% (P =.05); and refined graft-versus-host disease-free, relapse-free survival (rGRFS) was 33%, 39%, and 36% (P =.02). The incidence of grade II-IV acute GVHD was 25% in group 1, 39% in group 2, and 18% in group 3 (P <.01); incidence of chronic GVHD was 25%, 21%, and 24% (P =.50); relapse incidence was 36%, 37%, and 26% (P =.02); and nonrelapse mortality was 26%, 20%, and 21% (P =.35). On multivariate analysis, early start of immunosuppression therapy at day +1 followed by PTCY was associated with a better LFS (hazard ratio [HR],.58; P =.02) and improved rGRFS (HR,.62; P =.02). In this study, the timing of immunosuppression influenced the outcomes of haplo-HSCT with PTCY. An early start of CSA + MMF with PTCY administered on days +3 and +5 improves LFS and rGRFS. [ABSTRACT FROM AUTHOR]

• PBSC graft is associated with reduced mortality relative to BM cells for patients with HL undergoing haplo-SCT with PT-Cy. • Acute and chronic GVHD did not differ between PBSC and BM grafts. • A lower number of patients receiving PBSC haplo-SCT died because of disease relapse relative to BM graft. Haploidentical stem cell transplantation (haplo-SCT) with post-transplant cyclophosphamide (PT-Cy) represents a potential curative strategy for patients with Hodgkin lymphoma (HL) when a matched related or unrelated donor is not available. The role of graft source, either bone marrow (BM) or peripheral blood stem cells (PBSCs), in this setting has not been fully elucidated. We performed a retrospective study on 91 patients with HL to compare the outcome after BM (n = 53) or PBSC (n = 38) transplant. Eighty-nine patients engrafted with no difference between BM and PBSCs in terms of median time for neutrophil (20 versus 20 days, P =.405) and platelet (26 versus 26.5 days, P =.994) engraftment. With a median follow-up of 40.2 months, 100-day cumulative incidences of grades II to IV acute graft-versus host disease (GVHD) and grades II to IV acute GVHD were 24% and 4%, respectively. Graft source was not associated with a different risk of acute GVHD both by univariate and multivariate analyses. Consistently, 1-year cumulative incidence of chronic GVHD was 7% with no differences between the 2 graft types (P =.761). Two-year rates of overall survival (OS), progression-free survival (PFS), nonrelapse mortality, and GVHD/relapse-free survival (GRFS) were 67%, 58%, 20%, and 52%, respectively. By univariate analysis, pretransplant disease status was the main variable affecting all outcomes. By multivariate analysis, PBSCs resulted in a protective factor for OS (hazard ratio [HR],.29; P =.006), PFS (HR,.38; P =.001), and GRFS (HR,.44; P =.020). The other independent variables affecting the final outcome were pretransplant disease status and hematopoietic cell transplant–specific comorbidity index. In conclusion, when planning a haplo-SCT with PT-Cy for patients with poor-risk HL, graft type is an important variable to take into account when selecting the best available donor. [ABSTRACT FROM AUTHOR]

• Cyclophosphamide plus granulocyte colony-stimulating factor (G-CSF) and G-CSF were excellent for cell mobilization. • The 2 approaches were able to harvest a sufficient CD34+ cell dose. • Both regimens allowed a good and rapid engraftment. Autologous peripheral blood stem cell transplantation should be considered first-line therapy in young patients with POEMS. The best protocol to collect peripheral blood stem cells remains to be defined, because of the disease rarity and the heterogeneity of published case series. We collected clinical and laboratory data from 25 patients undergoing mobilization, of whom 11 were mobilized using cyclophosphamide (CY) followed by granulocyte colony-stimulating factor (G-CSF) and 14 patients using G-CSF. The incidence of poor mobilization was low and not statistically different between the 2 groups. Both schemes (CY plus G-CSF versus G-CSF alone) were able to harvest a sufficient CD34+ cell dose. [ABSTRACT FROM AUTHOR]

We evaluated the impact of unidirectional donor versus recipient killer cell immunoglobulin-like receptor (KIR)–ligand mismatch (KIR-Lmm) on the outcomes of T cell–replete haploidentical stem cell transplantation (Haplo-SCT) with post-transplant cyclophosphamide (PT-Cy) in a cohort of 144 patients treated for various hematologi diseases. We separately analyzed 81 patients in complete remission (CR group) and 63 with active disease (no CR group) at the time of Haplo-SCT. One-third of patients in each group had KIR-Lmm. In the no CR group, KIR-Lmm was associated with a significantly lower incidence of relapse (hazard ratio, .21; P  = .013) and better progression-free survival (hazard ratio, .42; P  = .028), with no significant increase in graft-versus-host disease incidence or nonrelapse mortality. In contrast, in the CR group no benefit of KIR-Lmm was observed. Our results encourage considering KIR-Lmm as an additional tool to improve donor selection for T cell–replete Haplo-SCT with PT-Cy, especially in patients with high-risk diseases. [ABSTRACT FROM AUTHOR]

Allogeneic hematopoietic stem cell transplantation (SCT) represents a potential curative strategy for patients with Hodgkin lymphoma (HL) relapsing after autologous SCT (ASCT), but the incidence of disease relapse is still high. We performed a retrospective study on 64 patients with HL relapsing after ASCT to compare outcomes after HLA-identical SCT (HLAid-SCT; n = 34) and haploidentical SCT with post-transplantation cyclophosphamide (PT-Cy) (Haplo-SCT; n = 30). All patients engrafted, with a significantly shorter median time for neutrophil and platelet engraftment after HLAid compared with Haplo-SCT (14 days versus 19 days and 11 days versus 23 days, respectively; P  < .005). With a median follow-up of 47 months, 3-year overall survival (OS), 3 -year progression-free survival (PFS), and 1-year nonrelapse mortality (NRM) were 53%, 44% and 17%, respectively. Recipients of Haplo-SCT were less likely to experience disease relapse (3-year cumulative incidence of relapse, 13% versus 62%; P  = .0001) and chronic graft- versus-host disease (GVHD; 3% versus 32%; P  = .003), resulting in improved PFS (60% versus 29%; P  = .04) and GVHD-free/relapse-free survival (47% versus 17%; P  = .06). The 3-year OS did not differ between the 2 groups (56% versus 54%; P  not significant), and NRM was higher after Haplo-SCT, but the difference did not reach statistical significance (26% versus 9%; P  = .09). On multivariate Cox regression analysis, receipt of Haplo-SCT (hazard ratio [HR], .17; P  = .02) and achieving optimal disease control (complete remission before SCT: HR, .6; P  < .0001) were the only independent variables associated with a reduced risk of disease relapse. Haplo-SCT is a valid option for patients with HL relapsing after ASCT, with a reduced incidence of relapse compared with HLAid SCT. [ABSTRACT FROM AUTHOR]

Abstract: It has been reported that chronic graft-versus-host disease (cGVHD) is associated with significant morbidity and mortality after allogeneic stem cell transplantation (allo-SCT). The risk of relapse is generally reduced when cGVHD is present, but prognosis may be affected by increased toxicity and/or risk of infection associated with immunosuppressive treatment (IST). We performed a longitudinal data analysis of cGVHD, including the evolution of cGVHD itself over time in response to IST, in a single-center cohort of 313 consecutive patients undergoing allo-SCT. We found that lack of sustained response without withdrawal of IST within 6 months of cGVHD development was associated with higher transplantation-related mortality (hazard ratio, 2.32; 95% confidence interval, 1.24-4.33) compared with cGVHD-free patients. Conversely, response conferred better overall survival (hazard ratio, 0.42; 95% confidence interval, 0.18-0.95). Our analytical approach allowed us to integrate the evolution of cGVHD in a predictive model of transplantation outcome; notably, remission associated with permanent discontinuation of IST within the first 6 months from the occurrence of cGVHD seemed to correlate most closely with final outcome. Further confirmation from larger studies is needed. [Copyright &y& Elsevier]

Donor lymphocyte infusions (DLI) can induce remission in patients with hematologic malignancies who relapse after allogeneic stem cell transplantation. However, graft-vs-host disease (GVHD) remains a major complication of this strategy. We have used escalating doses of DLI for many years, and wanted to assess the risk factors for GVHD and transplant-related mortality as well as disease outcomes according to the reason for DLI. We analyzed 65 patients who received a total of 111 DLI for different reasons and at different intervals after transplantation. Median number of DLI was 2 (range, 1–4), median interval between transplantation and DLI was 9 months (range, 1–41 months) and median number of infused CD3+ cells/kg recipient body weight was 2.5 × 107 (range, 1 × 106–11.8 × 107). Reasons for DLI were relapse or progression in 37 patients (57%), residual disease in 15 patients (23%), and persistence of mixed chimerism in 13 patients (20%). Seven patients (11%) developed acute GVHD grade II to IV and 5 patients (8%) developed extensive chronic GVHD. In univariate analysis, we could identify a transplantation–DLI interval ≤6 months, the dose of DLI (≥1 × 107), and DLI number as predictive factors of GVHD. In multivariate analysis, these results were confirmed only for the transplantation–DLI interval (hazard ratio = 19.48; 2.23–170.34; p = 0.007). Our findings indicate that this form of adoptive immunotherapy is well tolerated and induces a low incidence of GVHD and transplant-related mortality, supporting further investigation as an upfront modality to enhance the graft-vs-tumor response in high-risk patients. [ABSTRACT FROM AUTHOR]

Objective: The development of reduced-intensity conditioning regimens rather than myeloablative regimens for allogeneic stem cell transplantation has led to decreased treatment-related mortality and increased use of this treatment modality, especially in older patients with hematological malignancies. No randomized controlled trials have been performed resulting in determining effectiveness on phase II studies, which rarely report on long-term survival. Materials and Methods: In an attempt to address this limitation, we analyzed a single-center cohort of 100 consecutive patients with hematological malignancies undergoing allogeneic stem cell transplantatioon from a human leukocyte antigen–matched related donor with median follow-up of 60 months. The reduced-intensity conditioning regimen consisted of oral Busulfan, rabbit anti-thymocyte globulin, and Fludarabin. Results: Median age was 50 years (range, 18–64 years). The incidences of acute and chronic graft-vs.-host disease were 43% and 81%, respectively. The probability of nonrelapse mortality at 1 and 5 years was 15% and 25%, respectively. Nonrelapse mortality was adversely associated with acute graft-vs.-host disease (hazard ratio = 6; p = 0.0002). Of the 52 patients with measurable disease, 37 (71%) achieved a response. Relapse/progression occurred at a median of 11 months (range 1–52 months) in 21 patients, for a cumulative incidence of 22%. The probability of overall survival and progression-free survival at 5 years were 60% and 54%, respectively. Overall survival and progression-free survival were favorably influenced by having had previous autologous stem cell transplantation and a low CD34+ cell dose. Overall survival, progression-free survival, and nonrelapse mortality improved over time in this cohort of patients. Conclusions: These results are encouraging for populations different in term of age, diagnosis, and disease status. [ABSTRACT FROM AUTHOR]

The use of post-transplant cyclophosphamide (PTCy) is highly effective in preventing graft-versus-host disease (GVHD) in the haploidentical (Haplo) transplant setting and is being increasingly used in matched sibling (MSD) and matched unrelated (MUD) transplants. There is no information on the impact of donor types using homogeneous prophylaxis with PTCy. We retrospectively analysed outcomes of adult patients with acute myeloid leukemia (AML) in first complete remission (CR1) that received a first allogeneic stem cell transplantation (SCT) with PTCy as GVHD prophylaxis from MSD (n=215), MUD (n=235) and Haplo (n=789) donors registered in the EBMT database between 2010 and 2017. The median follow up period of the entire cohort was 2 years. Median age of patients was 52 years (range, 18-76), 693 (56%) were male and 928 (78%) were CMV seropositive. 47 (6%),543 (66%) and 239 (29%) had standard, intermediate and high risk cytogenetics, respectively. Peripheral blood (PB) was used in 814 (66%) patients and myeloablative conditioning (MAC) in 739 (59%). Compared to MSD and MUD, Haplo patients were older (p < 0.001), received more frequently MAC (p = 0.006), GvHD prophylaxis with PTCy combined with 2 other immunosuppressive drugs (p < 0.001) and bone marrow as stem cell source (p < 0.001). The cumulative incidence of 100-day acute GVHD grade II-IV and III-IV, and 2-year chronic and chronic extensive GVHD were 25% (95% CI 23-28), 9% (95% CI 7-10), 31% (95% CI 28-34) and 12% (95% CI 10-14), respectively. At 2 years, the cumulative incidence of relapse and non-relapse mortality (NRM) and the probability of leukemia-free survival (LFS) and overall survival (OS) were 25% (95% CI 22-28), 19% (95% CI 17-21), 56% (95% CI 53-59) and 63% (95% CI 60-66), respectively. On multivariable analysis, Haplo-SCT carried a significantly increased risk of acute grade II-IV GVHD (HR 1.6; 95% CI 1.1-2.4) and NRM (HR 2.6; 95% CI 1.5-4.5) but a lower risk of relapse (HR 0.7; 95% CI 0.5-0.9) that translated to no change in LFS (HR 1.1; 95% CI 0.8-1.4) or GVHD/relapse-free survival (HR 1; 95% CI 0.8-1.3). Interestingly, the use of PB was associated with an increased risk of acute (HR 1.9; 95% CI 1.4-2.6) and chronic GVHD (HR 1.7; 95% CI 1.2-2.4) but a lower risk of relapse (HR 0.7; 95% CI 0.5-0.9). Variables associated with better LFS were MAC, good or intermediate risk cytogenetics and good performance status,while higher recipient´s age and positive CMV serostatus of the recipient showed worse outcome. The use of PTCy in patients with AML in CR1 receiving SCT from MSD, MUD and Haplo is safe and effective and rates of GVHD are low, especially chronic. HLA mismatch in Haplo has a negative impact on acute GVHD and NRM in this setting but also offers increased anti-leukemic efficacy. As seen in other transplant scenarios, PB is associated with more GVHD and less relapse. [ABSTRACT FROM AUTHOR]

Introduction Allogeneic stem-cell transplantation (SCT) is curative therapy in AML by providing intensive chemotherapy and enhancing a graft-versus-leukemia (GVL) effect. The GVL effect is usually closely associated with GVHD. The use of haploidentical SCT (haploSCT) is rapidly increasing due to the introduction of non-T depleted methods, in particular with post-transplant cyclophosphamide (PTCy), with similar outcomes as following other donor sources. There is no data whether GVL after haploSCT is associated with GVHD as in matched donor SCT. Methods We assessed the impact of acute and chronic GVHD on SCT outcomes following non-T depleted haploSCT with PTCy, by using a series of landmark analyses. Results The study included 605 patients with AML in CR1 (73%) or CR2 (27%) after haploSCT with PTCy, given during the years 2009-2016. The median age was 53 years (18-76). The overall rate of acute GVHD grade II-IV and III-IV was 28.4% and 8.0%, respectively. The rates of chronic GVHD all grades and extensive were 32.7% and 12.3%, respectively. The 2-year leukemia-free survival (LFS) was 59.9%. 509 patients were alive and leukemia-free 100 days after SCT; 366 had no prior acute GVHD at this landmark, 107 had acute GVHD grade II and 36 had grade III-IV. The subsequent relapse rate was 20.3%, 18.3% and 11.9%, respectively (P=0.60). The subsequent non-relapse mortality (NRM) rate was 10.3%, 19.0% and 35.7%, respectively (P<0.001). LFS was 69.4%, 62.6% and 52.4%, respectively (P=0.01). Multivariate analysis showed that acute GVHD grade II was not associated with subsequent relapse (Hazard ratio (HR) 1.02, P=0.93), had borderline association with NRM (HR 1.79, P=0.09) and no association with LFS (HR 1.28, P=0.27). Acute GVHD grade III-IV was not associated with subsequent relapse (HR 0.92, P=0.87), but was associated with higher NRM (HR 5.23, P<0.001) and lower LFS (HR 2.35, P=0.003). 393 patients were alive and leukemia-free 6 months after SCT; 316 had no prior chronic GVHD, 55 had limited and 22 extensive chronic GVHD. The subsequent relapse rate was 14.3%, 9.2% and 23.9%, respectively (P=0.60). The subsequent NRM rate was 7.3%, 10.4% and 31.7%, respectively (P=0.003). LFS rate was 78.4%, 80.4% and 44.4%, respectively (P=0.01). Multivariate analysis showed that limited grade chronic GVHD was not associated with subsequent relapse (HR 0.69, P=0.44), NRM (HR 1.43, P=0.55) or LFS (HR 0.88, P=0.74). Extensive chronic GVHD was not associated with subsequent relapse (HR 1.44, P=0.56) but was associated with higher NRM (HR 5.77, P=0.004) and lower LFS (HR 2.75, P=0.01). Conclusions Acute and chronic GVHD of any grade were not associated with subsequent relapse. Acute GVHD grade III-IV and extensive chronic GVHD were associated with higher NRM and lower LFS. GVL is thus not closely associated with GVHD after non T-depleted haploSCT with PTCy. Future novel strategies for prevention of significant GVHD are warranted. [ABSTRACT FROM AUTHOR]