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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]

• 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]

Relapse/refractory Hodgkin lymphoma patients are still a clinical concern. Indeed, despite more effective first-line chemotherapy regimens and better stratification of unresponsive patients by clinical factors and use of early PET, roughly one-third of such patients need salvage chemotherapy and consolidation with high-dose chemotherapy. In this paper, the authors review the different salvage treatments, with special emphasis on newer combinations with brentuximab vedotin or check point inhibitors. The overall response rate is constantly increasing, with a complete remission rate approaching 80%. Functional response evaluation by PET imaging is a strong predictive factor of longer survival, and more sophisticated tools, such as detection of circulating tumour DNA, are emerging to refine the disease-status assessment after treatment. Consolidation by high-dose chemotherapy is still considered the standard of care in chemosensitive patients, leading to a high fraction of patients towards long-term disease control. Maintenance therapy with BV is now approved, reducing disease relapse/progression. An increasing number of Hodgkin lymphoma patients will be cured after first- and second-line therapy, and long-term toxicity needs to be continuously assessed and avoided. [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]

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. [ABSTRACT FROM AUTHOR]

Allogeneic (allo) hematopoietic cell transplantation (HCT) currently represents the only potentially curative therapy for patients affected by multiple myeloma (MM). Up to 30% of patients in western countries do not have a matched donor. Haploidentical HCT (haplo-HCT) may be an option, but currently, there are little available data regarding this treatment. We analyzed survival outcomes of 30 heavily pretreated MM patients who received haplo-HCT with post-transplantation cyclophosphamide as graft-versus-host-disease (GVHD) prophylaxis. Median neutrophil and platelet engraftments at day +30 were 87% (95% confidence interval [CI], 66% to 95%) and 60% (95% CI, 40% to 75%), respectively. The cumulative incidences of relapse or progression of disease (PD) and nonrelapse mortality at 18 months were 42% (95% CI, 23% to 59%) and 10% (95% CI, 2% to 24%), respectively. The cumulative incidence of grade II to IV acute GVHD at day +100 was 29% (95% CI, 14% to 47%). The cumulative incidence of chronic GVHD at 18 months was 7% (95% CI, 1% to 21%). With a median follow-up in survivors of 25 months (range, 15 to 73 months), the 18-month progression-free survival (PFS) and overall survival (OS) were 33% (95% CI, 17% to 50%) and 63% (95% CI, 44% to 78%), respectively. No differences were observed between peripheral blood and bone marrow graft in terms of engraftment, GVHD, or PD incidence. Chemorefractory disease at transplantation was associated with a lower/reduced 18-month PFS (9% versus 47%, P  = .01) and OS (45% versus 74%, P  = .03). This was explained by a higher PD incidence (55% versus 33%, P  = .05). In this multicenter study, we report encouraging results with haplo-HCT for patients with heavily pretreated MM. [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]

Early T-cell reconstitution following allogeneic transplantation depends on the persistence and function of T cells that are adoptively transferred with the graft. Posttransplant cyclophosphamide (pt-Cy) effectively prevents alloreactive responses from unmanipulated grafts, but its effect on subsequent immune reconstitution remains undetermined. Here, we show that T memory stem cells (TSCM), which demonstrated superior reconstitution capacity in preclinical models, are the most abundant circulating T-cell population in the early days following haploidentical transplantation combined with pt-Cy and precede the expansion of effector cells. Transferred naive, but not TSCM or conventional memory cells preferentially survive cyclophosphamide, thus suggesting that posttransplant TSCM originate from naive precursors. Moreover, donor naive T cells specific for exogenous and self/tumor antigens persist in the host and contribute to peripheral reconstitution by differentiating into effectors. Similarly, pathogen-specific memory T cells generate detectable recall responses, but only in the presence of the cognate antigen. We thus define the cellular basis of T-cell reconstitution following pt-Cy at the antigen-specific level and propose to explore naive-derived TSCM in the clinical setting to overcome immunodeficiency. [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]

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]

The author focuses on the re-discovery of the natural killer (NK) cell allo-reactivity in the solid tumor therapy.

This retrospective study evaluated whether early 2-[fluorine-18]fluoro-2-deoxy-D-glucose positron emission tomography (FDG-PET) after two cycles of salvage chemotherapy (PET2) could predict survival after high-dose chemotherapy (HDC). Twenty-four Hodgkin lymphoma (HL) patients were included. PET2 was negative in 58% and positive in 42% of patients. Ninety per cent of patients (9/10) with positive PET2 relapsed after HDC while all but one patient with negative PET2 maintained a complete remission. The 2-year progression-free survival was 93% vs. 10% for patients with negative and positive PET2, respectively ( P < 0.001). This study shows that interim PET can predict the outcome after high-dose chemotherapy in HL patients. [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]

Background: We analysed the feasibility and efficacy of allogeneic stem cell transplantation (allo-SCT) with reduced-intensity conditioning (RIC) in patients with refractory or progressive Hodgkin's disease (HD) after high-dose chemotherapy (HDCT). Patients and methods: Fourteen patients with HD received allo-SCT with RIC: eleven patients had a human leucocytes antigen-identical related donor and three a matched unrelated donor. Six had chemoresistant disease and eight had chemosensitive one at the time of transplantation. All patients received a fludarabine-based RIC. Results: All patients engrafted and full donor chimerism was achieved in all patients. Grade II acute graft-vs.-host disease (GvHD) developed in six of the 14 patients (43%). Chronic GvHD developed in eight of the 13 patients (61%). There was neither early nor late treatment-related mortality (TRM). With a median follow-up of 21 months (range 3–74), 10 of the 14 patients were alive (71%). Estimated overall survival at 1 and 2 yr was 93% and 73%, respectively, for the whole population, 83% and 44% respectively for patients with chemoresistant disease and 100% for those with chemosensitive disease. Estimated progression-free survival at 1 yr was 36%; 62.5% for chemosensitive patients and 0% for those with chemoresistant disease. Conclusions: In conclusion, allo-SCT with fludarabine-based RIC is a feasible procedure, without TRM in HD patients relapsed and refractory after HDCT. Even if several questions are still open, this approach should proposed for these poor prognosis patients. [ABSTRACT FROM AUTHOR]

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]

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]

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.

A letter to the editor is presented in response to the article "Successful treatment of thrombotic microangiopathy after haematopoietic stem cell transplantation with rituximab," by W. Y. Au and colleagues.

A letter to the editor is presented in response to a study on antibiotic prophylaxis with levofloxacin reducing the incidence of fever, probable infection, and hospitalization among tumor patients by researcher Michael Cullen and colleagues in the September 8, 2005 issue.

Purpose: To evaluate the dosimetric consequences of inaccurate isocenter positioning during treatment of total marrow (lymph-node) irradiation (TMI-TMLI) using volumetric modulated arc therapy (VMAT). Methods: Four patients treated with TMI and TMLI were randomly selected from the internal database. Plans were optimized with VMAT technique. Planning target volume (PTV) included all the body bones; for TMLI, lymph nodes and spleen were considered into the target, too. Dose prescription to PTV was 12 Gy in six fractions, two times per day for TMI, and 2 Gy in single fraction for TMLI. Ten arcs on five isocenters (two arcs for isocenter) were used to cover the upper part of PTV (i.e., from cranium to middle femurs). For each plan, three series of random shifts with values between -3 and +3 mm and three between -5 and +5 mm were applied to the five isocenters simulating involuntary patient motion during treatment. The shifts were applied separately in the three directions: left-right (L-R), anterior-posterior (A-P), and cranial-caudal (C-C). The worst case scenario with simultaneous random shifts in all directions simultaneously was considered too. Doses were recalculated for the 96 shifted plans (24 for each patient). Results: For all shifts, differences <0.5% were found for mean doses to PTV, body, and organs at risk with volumes >100 cm3. Maximum doses increased up to 15% for C-C shifted plans. PTV covered by the 95% isodose decreased of 2%-8% revealing target underdosage with the highest values in C-C direction. Conclusions: The correct isocenter repositioning of TMI-TMLI patients is fundamental, in particular in C-C direction, in order to avoid over- and underdosages especially in the overlap regions. For this reason, a dedicated immobilization system was developed in the authors' center to best immobilize the patient. [ABSTRACT FROM AUTHOR]

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]

• 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]

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]

• Outcomes of 122 haploidentical hematopoietic cell transplantations with post-transplantation cyclophosphamide for T cell acute lymphoblastic leukemia are reported. • Survival was mostly affected by disease status, being significantly better in first complete remission • Outcomes were not affected by conditioning, calling into question the need for total body irradiation. Allogeneic hematopoietic cell transplantation (HCT) is recommended in high-risk patients with T cell acute lymphoblastic leukemia (T-ALL). For patients without an HLA-identical donor, haploidentical (haplo-) HCT is becoming the leading source of stem cell donation. However, data are scarce on predictive factors for outcome in that setting. We identified 122 adults (20% female; median age, 31 years; range, 18 to 68 years) with T-ALL who underwent haplo-HCT with post-transplantation cyclophosphamide (ptCy) between 2010 and 2017. The median duration of follow-up of living patients was 23 months. The 2-year incidences of relapse and nonrelapse mortality were 45% and 21%, respectively. The 2-year leukemia-free survival (LFS), overall survival (OS), and graft-versus-host disease, relapse-free survival (GRFS) were 34%, 42%, and 27%, respectively. The 2-year LFS and OS were highly influenced by disease status at transplantation, being 49% and 55%, respectively, for patients in first complete remission (CR1); 34% and 50%, respectively, for those in second CR (CR2); and 8% and 12%, respectively, for patients with active disease. On multivariate analysis, only disease status was found to affect LFS and OS. Transplantation in CR2 negatively affected LFS, whereas active disease at the time of haplo-HCT negatively affected LFS and OS. In conclusion, haplo-HCT with ptCy produced encouraging results in this challenging disease, particularly when performed in patients in CR. Despite the limitation of the small sample size, our results were not affected by the type of conditioning, calling into question the need for total body irradiation-based myeloablative conditioning in that setting. [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]

• 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]

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

• 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]

Abstract: Background: Invasive fungal infections (IFI) represent a common side effect of allogeneic hematopoietic stem cell transplant (allo‐SCT), resulting in increased non relapse mortality (NRM) and reduced overall survival (OS) rates. Seventy‐five days of Fluconazole 400 mg/d represents the standard primary antifungal prophylaxis (PAP) after allo‐SCT, especially for low‐risk transplants. However, the ideal dosage of fluconazole has never been tested. Methods: Here, we report the experience of our institution on 113 consecutive patients receiving an allo‐SCT from a HLA identical sibling between 1999 and 2015, where PAP consisted of fluconazole 100 mg/d only during the pre‐engraftment phase. At the time of transplant, all patients were considered at low‐risk for mold infection according to ECIL‐5 guidelines. Results: Cumulative incidence of possible‐probable‐proven IFI was 11.7%, while proven‐probable (PP‐IFI) occurred in 5.5% of patients by day 100 post transplant. Of note, only 1 patient developed invasive Candidiasis due to a non‐albicans strain and stool‐screening tests were negative for colonization by Candida albicans species. The incidence of 1‐year acute and 2‐year chronic graft‐versus‐host‐disease (GVHD) was 30% and 45%, respectively. Three‐year OS and 1‐year NRM were 53% and 11.3%, respectively. Conclusion: In summary, fungal prophylaxis with fluconazole 100 mg/d results in very low incidence of PP‐IFI, GVHD and NRM in low‐risk allo‐SCT. [ABSTRACT FROM AUTHOR]

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. [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]

Background: Incidence of graft-versus-host disease (GVHD) in haploidentical bone marrow (BM) transplants using posttransplantion cyclophosphamide (PT-Cy) is low, whereas GVHD using mobilized peripheral blood stem cells (PBSC) ranges between 30% and 40%.Methods: To evaluate the effect of stem cell source in haploidentical transplantation with PT-Cy, we analyzed 451 patients transplanted for acute myeloid leukemia or acute lymphoblastic leukemia reported to the European Society for Blood and Marrow Transplantation.Results: BM was used in 260 patients, and PBSC were used in 191 patients. The median follow-up was 21 months. Engraftment was lower in BM (92% vs 95%, P < 0.001). BM was associated with a lower incidence of stage II-IV and stage III-IV acute GVHD (21% vs 38%, P ≤ .01; and 4% vs 14%, P < .01, respectively). No difference in chronic GVHD, relapse, or nonrelapse mortality were found for PBSC or BM. The 2-year overall survival (OS) was 55% versus 56% (P = .57) and leukemia-free survival (LFS) was 49% versus 54% (P = .74) for BM and PBSC, respectively. On multivariate analysis, PBSC were associated with an increased risk of stage II-IV (hazard ratio [HR], 2.1; P < .001) and stage III-IV acute GVHD (HR, 3.8; P < .001). For LFS and OS, reduced intensity conditioning was the only factor associated with treatment failure (LFS: HR, 1.40; P = .04) and relapse (HR, 1.62; P = .02).Conclusion: In patients with acute leukemia in first or second remission receiving haploidentical transplantation with PT-Cy, the use of PBSC increases the risk of acute GVHD, whereas survival outcomes are comparable. Cancer 2018;124:1428-37. © 2018 American Cancer Society. [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]

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]

Background. Gram-negative bacteremia (GNB) is a major cause of illness and death after hematopoietic stem cell transplantation (HSCT), and updated epidemiological investigation is advisable. Methods. We prospectively evaluated the epidemiology of pre-engraftment GNB in 1118 allogeneic HSCTs (allo-HSCTs) and 1625 autologous HSCTs (auto-HSCTs) among 54 transplant centers during 2014 (SIGNB-GITMO-AMCLI study). Using logistic regression methods. we identified risk factors for GNB and evaluated the impact of GNB on the 4-month overall-survival after transplant. Results. The cumulative incidence of pre-engraftment GNB was 17.3% in allo-HSCT and 9% in auto-HSCT. Escherichia coli, Klebsiella pneumoniae, and Pseudomonas aeruginosa were the most common isolates. By multivariate analysis, variables associated with GNB were a diagnosis of acute leukemia, a transplant from a HLA-mismatched donor and from cord blood, older age, and duration of severe neutropenia in allo-HSCT, and a diagnosis of lymphoma, older age, and no antibacterial prophylaxis in auto-HSCT. A pretransplant infection by a resistant pathogen was significantly associated with an increased risk of posttransplant infection by the same microorganism in allo-HSCT. Colonization by resistant gram-negative bacteria was significantly associated with an increased rate of infection by the same pathogen in both transplant procedures. GNB was independently associated with increased mortality at 4 months both in allo-HSCT (hazard ratio, 2.13; 95% confidence interval, 1.45-3.13; P <.001) and auto-HSCT (2.43; 1.22-4.84; P = .01). Conclusions. Pre-engraftment GNB is an independent factor associated with increased mortality rate at 4 months after auto-HSCT and allo-HSCT. Previous infectious history and colonization monitoring represent major indicators of GNB. [ABSTRACT FROM AUTHOR]

Anti-programmed cell death protein 1 (PD-1) monoclonal antibodies are being increasingly tested in patients with advanced lymphoma. Following treatment, many of those patients are likely to be candidates for allogeneic hematopoietic stem cell transplant (HSCT). However, the safety and efficacy of HSCT may be affected by prior PD-1 blockade. We conducted an international retrospective analysis of 39 patients with lymphoma who received prior treatment with a PD-1 inhibitor, at a median time of 62 days (7-260) before HSCT. After a median follow-up of 12 months, the 1-year cumulative incidences of grade 2-4 and grade 3-4 acute graft-versus-host disease (GVHD) were 44% and 23%, respectively, whereas the 1-year incidence of chronic GVHD was 41%. There were 4 treatment-related deaths (1 from hepatic sinusoidal obstruction syndrome, 3 from early acute GVHD). In addition, 7 patients developed a noninfectious febrile syndrome shortly after transplant requiring prolonged courses of steroids. One-year overall and progression-free survival rates were 89% (95% confidence interval [CI], 74-96) and 76% (95% CI, 56-87), respectively. One-year cumulative incidences of relapse and nonrelapse mortality were 14% (95% CI, 4-29) and 11% (95% CI, 3-23), respectively. Circulating lymphocyte subsets were analyzed in 17 patients. Compared with controls, patients previously treated with PD-1 blockade had significantly decreased PD-1+ T cells and decreased ratios of T-regulatory cells to conventional CD4 and CD8 T cells. In conclusion, HSCT after PD-1 blockade appears feasible with a low rate of relapse. However, there may be an increased risk of early immune toxicity, which could reflect long-lasting immune alterations triggered by prior PD-1 blockade. [ABSTRACT FROM AUTHOR]

Anti-programmed cell death protein 1 (PD-1) monoclonal antibodies are being increasingly tested in patients with advanced lymphoma. Following treatment, many of those patients are likely to be candidates for allogeneic hematopoietic stem cell transplant (HSCT). However, the safety and efficacy of HSCT may be affected by prior PD-1 blockade. We conducted an international retrospective analysis of 39 patients with lymphoma who received prior treatment with a PD-1 inhibitor, at a median time of 62 days (7-260) before HSCT. After a median follow-up of 12 months, the 1-year cumulative incidences of grade 2-4 and grade 3-4 acute graft-versus-host disease (GVHD) were 44% and 23%, respectively, whereas the 1-year incidence of chronic GVHD was 41%. There were 4 treatment-related deaths (1 from hepatic sinusoidal obstruction syndrome, 3 from early acute GVHD). In addition, 7 patients developed a noninfectious febrile syndrome shortly after transplant requiring prolonged courses of steroids. One-year overall and progression-free survival rates were 89% (95% confidence interval [Cl], 74-96) and 76% (95% Cl, 56-87), respectively. One-year cumulative incidences of relapse and nonrelapse mortality were 14% (95% Cl, 4-29) and 11% (95% Cl, 3-23), respectively. Circulating lymphocyte subsets were analyzed in 17 patients. Compared with controls, patients previously treated with PD-1 blockade had significantly decreased PD-1+ T cells and decreased ratios of T-regulatory cells to conventional CD4 and CD8 T cells. In conclusion, HSCT after PD-1 blockade appears feasible with a low rate of relapse. However, there may be an increased risk of early immune toxicity, which could reflect long-lasting immune alterations triggered by prior PD-1 blockade. [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]

Presents a letter to the editor about the high incidence of hemostatic interference in cancer patients treated with FOLFOX regimen and concomitant minidose of warfarin.

BACKGROUND The presence of human leukocyte antigen donor-specific antibodies (DSAs) increases the risk of graft failure in T-cell-replete haploidentical hematopoietic stem cell transplantation (haplo-HSCT) CASE REPORT A 49-year-old female with high-risk acute myeloid leukemia in first complete remission received a haplo-HSCT from her daughter. Pretransplant recipient screening examination showed high DSAs levels against unshared class I leukocyte antigens. RESULTS The patient underwent a desensitization program consisting of plasma exchange (PEX), polyvalent intravenous (IV) immunoglobulins, and IV tacrolimus and mycophenolate mofetil (MMF). This protocol resulted in the disappearance of the DSA anti HLA B41. Engraftment was prompt with stable full donor chimerism. CONCLUSIONS This case report suggests that the adopted scheme is safe for reducing DSA levels and facilitating donor engraftment in patients scheduled for haplo-HSCT. [ABSTRACT FROM AUTHOR]

It has recently been shown that a T cell–replete allogeneic (allo) hematopoietic stem cell transplantation (HSCT) from a haploidentical donor (haplo-ID) could be a valid treatment for hematological malignancies. However, little data exist concerning older populations. We provided transplantation to 31 patients over the age of 55 years from a haplo-ID and compared their outcomes with patients of the same ages who underwent transplantation from a matched related (MRD) or an unrelated donor (UD). All 3 groups were comparable, except for their conditioning. Patients in haplo-ID group received 2 days of post-transplantation high-dose cyclophosphamide followed by cyclosporine A and mycophenolate mofetil, whereas patients in other groups received pretransplantation antithymocyte globulin, cyclosporine A, and additional mycophenolate mofetil in case of 1-antigen mismatch. All patients but 1 in the haplo-ID group engrafted. The incidence of grades 2 to 4 acute graft-versus-host disease (GVHD) was not statistically different between recipients from haplo-ID (cumulative incidence, 23%) and MRD (cumulative incidence, 21%) transplantations but it was lower than after UD HSCT (cumulative incidence, 44%). No patient in the haplo-ID group developed severe chronic GVHD, compared with cumulative incidences of 16% and 14% after MRD ( P = .02) and UD ( P = .03) grafts, respectively. The cumulative incidences of relapse were similar in the 3 groups, whereas nonrelapse mortality after UD HSCT was 3-fold higher than after haplo-ID or MRD HSCT. Overall, 2-year overall survival (70%), progression-free survival (67%), and progression and severe chronic GVHD–free survival (67%) probabilities after haplo-ID did not statistically differ from MRD transplantation (78%, 64%, and 51%, respectively), although they were higher than after UD transplantation (51% [ P = .08], 38% [ P = .02], and 31% [ P = .007]). We conclude that T cell–replete haplo-ID HSCT followed by post-transplantation high-dose- cyclophosphamide in patients over 55 years is associated with promising results, similar to MRD HSCT, and is deserving prospective evaluation. [ABSTRACT FROM AUTHOR]