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Hemorrhagic cystitis (HC) is a highly impacting complication in allogeneic hematopoietic stem cell transplantation (HSCT), occurring in 12%–37% of patients. The impact of transplant‐ and patient‐specific variables has been described, with a possible role for JCV and BKV, which may be cooperating with cytomegalovirus (CMV). Here, we analyze 134 letermovir‐exposed, CMV‐free patients, treated with the same cyclophosphamide‐based graft‐versus‐host disease (GVHD) prophylaxis, describing risk factors for HC. The overall incidence of HC was 23%. Patients with HLA mismatched transplant, higher comorbidity score, and receiving three alkylating agents with TBF (thiotepa, busulfan, and fludarabine) conditioning regimen had a higher risk of HC in multivariate analysis (OR: 4.48, 6.32, and 1.32, respectively). A HC‐score including male gender, TBF conditioning, and HLA‐mismatch stratifies the risk of HC in the first 100 days after HSCT. The role of BKV and JCV was not highly impacting in those patients, suggesting a possible synergistic effect between CMV and JCV in causing HC. HC can be interpreted as the combination of patient‐related factors, chemotherapy‐related toxicities—especially due to alkylating agents—and immunological elements. [ABSTRACT FROM AUTHOR]

Purpose: Hemorrhagic cystitis (HC) is a frequent complication of allogeneic hematopoietic stem-cell transplantation (HSCT). HC worsens transplant outcomes and patient wellbeing in terms of pain, hospitalization, and need for supportive care. A deeper understanding of the risk factors of HC may lead to more intensive prevention in high-risk patients.Methods: In this report, we analyzed 237 consecutive patients who received HSCT with the aim of identifying possible risk factors for HC and their consequences, with a particular focus on transplant- and gender-related risk factors.Results: HC occurred in 17% of patients, with a higher incidence in males (21% vs 11%, p = 0.03). Risk factors identified for HC included age over 55 years, male recipient, HLA mismatch, reduced intensity conditioning, and cyclophosphamide-based graft-versus-host disease (GVHD) prophylaxis. Increased HC was seen in patients with grade II-IV acute GVHD and detectable BKV and JCV viruria. In a multivariate model, increased age remained significant (p = 0.013). Patients with HC had longer hospitalizations and increased non-relapse mortality (NRM). Among male recipients, independent risk factors for HC included age (p = 0.016) and prostate volume (p = 0.016). Prostatic hyperplasia (volume more than 40 cm3) occurred in 33% of male patients, of which 32% developed HC (compared with 16% of patients without prostatic hyperplasia; p = 0.032).Conclusions: Age is the most important risk factor for HC. Additional potential risk factors include cyclophosphamide-based GVHD prophylaxis and HLA mismatch. Among male recipients, prostatic hyperplasia is an additional independent risk factor. As HC is common and associated with prolonged hospitalization, more intensive prophylactic strategies should be considered in high-risk patients. [ABSTRACT FROM AUTHOR]

The aim of this review is to update the current status of allogeneic hemopoietic stem cell transplants (HSCT) for patients with myelofibrosis (MF). We have first summarized the issue of an indication for allogeneic HSCT, discussing several prognostic scoring systems, developed to predict the outcome of MF, and therefore to identify patients who will benefit of an allogeneic HSCT. Patients with low risk MF are usually not selected for a transplant, whereas patients with intermediate or high risk MF are eligible. A separate issue, is how to predict the outcome of HSCT: we will outline a clinical molecular myelofibrosis transplant scoring system (MTSS), which predicts overall survival, ranging from 90% for low risk patients, to 20% for very high risk patients. We will also discuss transfusion burden and spleen size, as predictors of transplant outcome. The choice of a transplant platform including the conditioning regimen, the stem cell source and GvHD prophylaxis, are crucial for a successful program in MF, and will be outlined. Complications such as poor graft function, graft failure, GvHD and relapse of the disease, will also be reviewed. Finally we discuss monitoring the disease after HSCT with donor chimerism, driver mutations and hematologic data. We have made an effort to make this review as comprehensive and up to date as possible, and we hope it will provide some useful data for the clinicians. [ABSTRACT FROM AUTHOR]

Gastrointestinal graft-versus-host disease (GvHD) represents a life-threatening complication after stem cell transplantation. Differential diagnosis between gut GvHD and other causes of diarrhea after HSCT is still subjected to endoscopy and histological findings. The research for a reliable biomarker for gut GvHD might allow an early diagnosis of this condition and a consequent prompt treatment that could reduce unfavorable outcomes. Recently, fecal calprotectin was reported as reliable marker of gut involvement. We would evaluate if serum instead of fecal calprotectin could be considered a possible biomarker of gut GvHD. Serum calprotectin was measured in a cohort of 54 patients submitted to allogeneic stem cell transplantation using ELISA assay. For a subset of 21 patients, calprotectin serum levels were compared with fecal calprotectin detection. Contrary to fecal calprotectin, we found only a trend to high level of serum calprotectin for GvHD development and gut involvement, but statistical difference was not reached. Fecal but not serum calprotectin could be considered as possible biomarker for gut GvHD. [ABSTRACT FROM AUTHOR]

Background GvHD is one of the major complication after stem cell transplantation affecting transplant-related mortality. Throughout the last years, many serum proteins were been proposed as possible biomarkers for GvHD. Aims We studied the trend of five of the most studied serum proteins to evaluate whether a correlation exists between proteins concentration and post-HSCT outcomes. Materials and methods We measured serum concentration of REG3α, ST2, B-cell activating factor (BAFF), CXCL9 and elafin in a cohort of 77 patients submitted to Hematopoietic allogeneic stem cell transplantation (HSCT) in our department. Blood samples were been collected at baseline, day +30, GvHD onset and GvHD resolution. Results REG3α levels showed an association only with acute GvHD. Elafin and ST2 levels varied according to both acute and chronic GvHD occurrence. BAFF concentration showed an inverse association with acute GvHD development. Interestingly, baseline BAFF and ST2 levels predicted post-HSCT survival. No associations were found for CXCL9. Conclusions Except for CXCL9, the protein levels seem to change according to GvHD development, independently from organ involvement and grading. Pretransplant ST2 and BAFF appeared to be predictors for survival after HSCT. [ABSTRACT FROM AUTHOR]

Background: Allogenic hematopoietic stem cell transplantation (allo-SCT) is the most effective post-remission treatment for adults with high-risk acute lymphoblastic leukemia (ALL). The aim of the study was to analyze results of unmanipulated haploidentical allo-SCT (haplo-SCT) for adults with ALL and to identify prognostic factors. Methods: We performed a retrospective analysis on 208 adults transplanted in EBMT centers from 2007 to 2014. Results: Median age at haplo-SCT was 32 years and median follow-up, 31 months. Forty-four percent of the patients were in first complete remission (CR1). Stem cell source was the bone marrow (BM) for 43% and peripheral blood (PB) for 57% of patients. Myeloablative conditioning (MAC) was used for 66% and reduced intensity regimen (RIC) for 34% of patients. GVHD prophylaxis was based on post-transplant cyclophosphamide (PT-Cy) for 118 (57%) or on antithymocyte-globulin (ATG) for 90 (43%) plus standard prophylaxis. One hundred eighty-four (92%) patients achieved engraftment. Cumulative incidence (CI) of grade II-IV acute-graft-versus-host-disease (GVHD) was 31%, grade III-IV 11%, and chronic GVHD 29%. Non-relapse mortality (NRM) and relapse-incidence (RI) were 32 and 37%, respectively. Overall survival (OS), leukemia-free survival (LFS), and GVHD-free, relapse-free-survival (GRFS) at 3 years were 33, 31, and 26%. For patients in CR1, OS, LFS, and GRFS were 52, 47, and 40%, respectively. Disease status was the main factor associated with transplant outcomes. Use of BM was independently associated with improvement in NRM, acute GVHD, GRFS, LFS, and OS. Conclusions: Unmanipulated haplo-SCT may be considered a valid option for adult patients with high-risk ALL lacking HLA identical donor preferably in early disease status. [ABSTRACT FROM AUTHOR]

Background: Myeloablative (MAC) and reduced-intensity conditioning (RIC) are established approaches for allogeneic stem cell transplantation (SCT) in acute myeloid leukemia (AML). Most deaths after MAC occur within the first 2 years after SCT, while patients surviving leukemia-free for 2 years can expect a favorable long-term outcome. However, there is paucity of data on the long-term outcome (beyond 10 years) and the pattern of late events following RIC due to the relative recent introduction of this approach. Methods: We analyzed long-term outcomes in a cohort of 1423 AML patients, age =50 years, after SCT from HLA-matched siblings, during the years 1997-2005, median follow-up 8.3 years (0.1-17). Results: The 10-year leukemia-free survival (LFS) was 31 % (95CI, 27-35) and 32 % (28-35) after MAC and RIC, respectively (P = 0.57). The 10-year GVHD/ relapse-free survival (GRFS), a surrogate for quality of life was 22 % (18-25) and 21 % (18-24), respectively (P = 0.79). The 10-year non-relapse mortality (NRM) was higher and relapse rate was lower after MAC, throughout the early and late post-transplant course. The 10-year LFS among 584 patients surviving leukemia-free 2 years after SCT was 71 % (65-76) and 73 % (67-78) after MAC and RIC, respectively (P = 0.76). Advanced leukemia at SCT was the major predictor of LFS subsequent to the 2-year landmark. Relapse was the major cause of late death after both regimens; however, NRM and in particular chronic graft-versus-host disease and second cancers were more common causes of late death after MAC. Conclusions: Long-term LFS and GRFS are similar after RIC and MAC. Most events after RIC or MAC occur within the first 2 years after SCT. Patients who are leukemia-free 2 years after SCT can expect similar good subsequent outcome after both approaches. [ABSTRACT FROM AUTHOR]

Two-hundred and sixty-nine females aged ≤42 and undergoing an allogeneic stem cell transplant were retrospectively studied to assess the effect of age, conditioning regimen and chronic graft-versus-host disease (cGVHD) on resumption of stable menstrual cyclicity. Overall, a stable menstrual cyclicity was observed in 22% of cases. The cumulative probability of menses resumption was significantly age and conditioning regimen related. A statistically significant inverse correlation between cGVHD severity and menses resumption was observed only in univariate analysis. In patients with residual ovarian function, infertility was found in 43% and early menopause in 45%. An increased incidence of prematurity and low birth weight (LBW) was observed among the single spontaneous pregnancies. Follicle-stimulating hormone (FSH) and 17 beta-oestradiol levels were found to be inadequate to detect both early signs of menses resumption and menstrual stability. Our study confirms the crucial role of full dose total body irradiation (TBI) and age on menses recovery and fertility after haematopoietic stem cell transplantation (HSCT). The impact of severe cGVHD remains unclear. [ABSTRACT FROM AUTHOR]

Background: Increasing numbers of patients are receiving haplo-identical stem cell transplantation (haplo-SCT) for treatment of acute leukemia with reduced intensity (RIC) or myeloablative (MAC) conditioning regimens. The impact of conditioning intensity in haplo-SCT is unknown. Methods: We performed a retrospective registry-based study comparing outcomes after T-replete haplo-SCT for patients with acute myeloid (AML) or lymphoid leukemia (ALL) after RIC (n = 271) and MAC (n = 425). Regimens were classified as MAC or RIC based on published criteria. Results: A combination of post-transplant cyclophosphamide (PT-Cy) with one calcineurin inhibitor and mycophenolate mofetil (PT-Cy-based regimen) for graft-versus-host disease (GVHD) prophylaxis was used in 66 (25 %) patients in RIC and 125 (32 %) in MAC groups. Patients of RIC group were older and had been transplanted more recently and more frequently for AML with active disease at transplant. Percentage of engraftment (90 vs. 92 %; p = 0.58) and day 100 grade II to IV acute GVHD (24 vs. 29 %, p = 0.23) were not different between RIC and MAC groups. Multivariable analyses, run separately in AML and ALL, showed a trend toward higher relapse incidence with RIC in comparison to MAC in AML (hazard ratio (HR) 1.34, p = 0.09), and no difference in both AML and ALL in terms of non-relapse mortality (NRM) chronic GVHD and leukemia-free survival. There was no impact of conditioning regimen intensity in overall survival (OS) in AML (HR = 0.97, p = 0.79) but a trend for worse OS with RIC in ALL (HR = 1.44, p = 0.10). The main factor impacting outcomes was disease status at transplantation (HR ≥ 1.4, p ≤ 0.01). GVHD prophylaxis with PT-Cy-based regimen was independently associated with reduced NRM (HR 0.63, p=0.02) without impact on relapse incidence (HR 0.99, p = 0.94). Conclusions: These data suggest that T-replete haplo-SCT with both RIC and MAC, in particular associated with PT-Cy, are valid options in first line treatment of high risk AML or ALL. [ABSTRACT FROM AUTHOR]

Thiotepa is an alkylating compound with an antineoplastic and myeloablative activity and can mimic the effect of radiation. However, it is unknown whether this new regimen could safely replace the longestablished ones. This retrospective matched-pair analysis evaluated the outcome of adults with acute myeloid leukaemia in first complete remission who received myeloablative conditioning either with a thiotepa-based (n = 121) or a cyclophosphamide/total body irradiation-based (TBI; n = 358) regimen for allogeneic hematopoietic stem cell transplantation from an HLA-matched sibling or an unrelated donor. With a median follow-up of 44 months, the outcome was similar in both groups. Acute graft-versus-host disease grade II-IV was observed in 25% after thiotepa-containing regimen versus 35% after TBI (P = 0.06). The 2-yr cumulative incidence of chronic graft-versus-host disease was 40.5% for thiotepa and 41% for TBI (P = 0.98). At 2 yrs, the cumulative incidences of non-relapse mortality and relapse incidence were 23.9% (thiotepa) vs. 22.4% (TBI; P = 0.66) and 17.2% (thiotepa) vs. 23.3% (TBI; P = 0.77), respectively. The probabilities of leukaemia-free and overall survival at 2 yrs were not significantly different between the thiotepa and TBI groups, at 58.9% vs. 54.2% (P = 0.95) and 61.4% vs. 58% (P = 0.72), respectively. Myeloablative regimens using combinations including thiotepa can provide satisfactory outcomes, but the optimal conditioning remains unclear for the individual patient in this setting. [ABSTRACT FROM AUTHOR]

Background: In the setting of allogeneic human leukocyte antigen (HLA)-matched bone marrow transplantation, transplanting male patients with grafts from female donors has been associated with a higher incidence of graft-versus-host disease (GVHD) and of nonrelapse mortality (NRM). The aim of the current analysis was to compare transplantation outcomes in male patients given female unrelated cord blood (UCB) versus other gender combinations. Patients and methods: Data from 552 consecutive patients with acute myeloid leukemia (AML) given a single UCB transplantation between 2000 and 2014 were included. Results: In comparison with other gender combination, male patients given female UCB (n = 131) had a trend for a higher incidence of grades II-IV acute GVHD (33 versus 25 %, P = 0.08), a trend for a higher incidence of NRM (41 versus 33 %, P = 0.06), and a lower leukemia-free (LFS, 30 versus 41 %, P = 0.01) and overall survival (OS, 33 versus 45 %, P = 0.008). In multivariate analyses, taking into consideration all patients for which data on HLA-matching and cell dose transplanted were fully available (n = 363), male patients transplanted with a female UCB had a trend for a higher incidence of grade III-IV acute GVHD (hazard ratio (HR) = 2.0, P = 0.06), a trend for a higher NRM (HR = 1.5, P = 0.06), and a worse LFS (HR = 1.4, P = 0.04) and OS (HR = 1.3, P = 0.06). Conclusions: Our data suggest that male patients transplanted with female UCB might have higher risk of acute GVHD and of NRM leading to worse LFS and OS. These results should be confirmed in other large cohorts of patients before used for determining the choice of an UCB unit. [ABSTRACT FROM AUTHOR]

Background Extracorporeal photopheresis ( ECP) is an effective treatment for both acute and chronic graft-versus-host disease ( GVHD) in children and adults. Despite the large use of this treatment, a large heterogeneity in current application of ECP has been reported so far and recent evidence brought novel issues into some specific topics. Consensus-based recommendations ameliorate the appropriateness in daily clinical practice and, in turn, optimize the use of health care resources. Study Design and Methods Two Italian scientific societies, the Italian Society of Hemapheresis and Cell Manipulation ( SIdEM) and the Italian Group for Bone Marrow Transplantation ( GITMO), joined to develop and disseminate recommendations on appropriate application of ECP treatment in patients with GVHD. Accordingly, SIdEM and GITMO named an expert panel that first selected 16 questions that were considered relevant for clinical practice: the questions were subsequently addressed through a revision of the available literature and in consensus meetings. The whole group discussed the proposed recommendations according to the nominal group technique. Results The above-described approach in turn allowed the panel to agree on 47 practice recommendations. SIdEM and GITMO will disseminate such recommendations to the national transplant centers. Conclusion In conclusion, SIdEM and GITMO have made a scientific effort to provide a useful tool to physicians involved in the field, thus supporting daily clinical practice, as well as strategic decisions in the setting of ECP treatment of GVHD. [ABSTRACT FROM AUTHOR]

Acute graft- versus-host disease (GvHD) is a frequent complication of allogeneic haemopoietic stem cell transplantation (HSCT) and donor lymphocyte infusions (DLI). Its incidence and severity depends on several factors, such as prophylaxis method, donor/recipient matching, intensity of the conditioning regimen and composition of the graft. Significant progress has been made in recent years in understanding the pathogenesis of the disease, and some of these advances have been translated into clinical trials. First-line treatment of acute GvHD is based on corticosteroids, and produce sustained responses in 50–80% of patients depending on the initial severity. Non-responders are offered second-line therapy, with combinations of immunosuppressive agents, but 1-year survival is 30% in most large trials. New strategies explored include infusion of expanded mesenchymal stem cells (MSC), down regulation of antigen-presenting cells (APC) and suicide gene transduced T cells. Acute GvHD is complicated by severe immunodeficiency causing life-threatening infections. To date, GvHD has not been differentiated from the graft- versus-leukaemia effect. The present review will discuss some of these aspects. [ABSTRACT FROM AUTHOR]

Abstract: This is an update of a randomized study on antithymocyte globulin (ATG; Thymoglobulin) before transplantation in patients undergoing unmanipulated marrow transplantation from unrelated donors. The median follow-up for surviving patients is 5.7 years. At last follow-up, chronic graft-versus-host disease (GVHD) was scored in 60% of non-ATG and in 37% of ATG patients (P = .05), and extensive chronic GVHD was present in 41% and 15%, respectively (P = .01). Chronic lung dysfunction was diagnosed in 51% versus 19% of patients (P = .005). Forced vital capacity decreased significantly with time in non-ATG patients (P = .005), but not in patients who received ATG (P = .30). The proportion of patients with Karnofsky scores of ≥90% at 4 years was 57% versus 89% in non-ATG versus ATG patients (P = .03). The actuarial 6-year survival for all patients randomized was 31% versus 44% (non-ATG versus ATG; P = .80). The cumulative incidence of transplant-related mortality was 51% versus 41% (P = .70) and of relapse was 32% versus 40% (P = .90). For patients who survived 1 year, transplant-related mortality was 25% versus 3% (P = .03), and actuarial survival was 58% versus 85% (P = .09). In conclusion, the addition of ATG to cyclosporine/methotrexate provides significant protection against extensive chronic GVHD and chronic lung dysfunction, reduces late transplant mortality, and improves quality of life in patients undergoing unrelated donor transplantation. [Copyright &y& Elsevier]

Graft versus host disease (GvHD) is a frequent complication of allogeneic hemopoietic stem cell transplantation (HSCT), and of donor lymphocyte infusions (DLI): the acute form occurs within 100 days from HSCT or DLI, the chronic form beyond day +100. GvHD should be prevented rather than treated. There are several ways to prevent GvHD: remove donor T cells from the transplant (ex vivo T-cell depletion), administer T-cell antibodies to the patient (in vivo T-cell depletion), administer immunosuppressive drugs such as methotrexate, cyclosporin, tacrolimus, and mycofenolate (post-transplant immunosuppression). New strategies of GvHD prophylaxis include the infusion of expanded mesenchymal stem cells and downregulation of host antigen-presenting cells. First-line treatment of established GvHD is based on low-dose corticosteroids (0.5-2?mg/kg). Second-line therapy for steroid refractory GvHD is unsatisfactory. The early administration of T-cell antibodies and/or TNF antibodies and TNF soluble receptor may be successful in some cases, but they do not seem to fulfill the expectations. High-dose chemotherapy has not been explored thoroughly. Acute GvHD is complicated by infections that cause significant morbidity and mortality: prophylaxis, early diagnosis and treatment of infections are an integral part of GvHD management. We have considerably reduced the risk of acute GvHD over the past three decades: we need to further improve these results, with the final goal of dissecting, if possible, the graft versus host from the graft versus tumor effect.The Hematology Journal (2004) 5, 189-196. doi:10.1038/sj.thj.6200399 [ABSTRACT FROM AUTHOR]

Platelet recovery after allogeneic haemopoietic stem cell transplant (HSCT) and predictive factors were analysed in 342 patients with haematological malignancies. All patients were prepared with cyclophosphamide plus total body irradiation, and received an unmanipulated HSCT from an HLA-identical sibling (n = 270), a matched unrelated donor (n = 67) or an identical twin (n = 5). The source of stem cells was peripheral blood (n = 15) or bone marrow (n = 327). Graft-vs.-host disease (GvHD) prophylaxis consisted of cyclosporin A with or without methotrexate. The proportion of patients with < 50 × 109/l platelets on d +50, d +100, d +200 and d +365 after HSCT was 26%, 27%, 14% and 11% respectively. Thrombocytopenia was independent of the degree of complete donor chimaerism. Four variables were predictive of platelet recovery: donor type, acute GvHD, cytomegalovirus (CMV) infection and number of cells infused at transplant. Recipients of an unrelated graft had lower platelet counts (49 × 109/l) on d +50 than identical sibling grafts (108 × 109/l) (P < 0·001) and twin grafts (149 × 109/l) (P < 0·001). Patients with GvHD grades 0, I, II, III and IV had significantly different platelet counts on d +50 (153 × 109/l, 102 × 109/l, 85 × 109/l, 32 × 109/l and 22 × 109/l; P < 0·001) and thereafter. Thrombocytopenia was more frequent in patients with high-level CMV antigenaemia (> four positive cells/2 × 105) (P < 0·0001) and in patients who received a low cell dose at transplant (≤ 4·1 × 108/kg) (P = 0·009). Platelet counts predicted transplant-related mortality (TRM) and were higher at all time intervals in patients surviving the transplant. Patients with grade II GvHD and > 50 × 109/l platelets had a lower TRM than patients with grade... [ABSTRACT FROM AUTHOR]

Disparities at minor histocompatibility antigens (mHA) are thought to be responsible for acute graft-versus-host disease (aGVHD) in patients receiving bone marrow transplantation (BMT) from a human leucocyte antigen (HLA)-matched donor. Although some mHA have been identified in humans, their role in aGVHD has not. Patients (n = 150) receiving a BMT from an HLA-matched donor were investigated for a correlation between aGVHD and donor/recipient incompatibility for seven polymorphisms previously proposed for mHA (HA-1, H-Y, CD31-codon 125, CD31-codon 563, HPA-1, HPA-3 and HPA-5). Only mismatch at CD31-codon 563 predicted grade II–IV aGVHD. The risk derived from CD31-codon 563 mismatch was the same as that derived from the use of bone marrow from an unrelated donor. We suggest that donor/recipient compatibility at CD31-codon 563 should be added to HLA-typing for donor selection and/or adjustment of aGVHD prophylaxis. [ABSTRACT FROM AUTHOR]

Background: Experience using post-transplant cyclophosphamide (PT-Cy) as graft-versus-host disease (GVHD) prophylaxis in allogeneic stem cell transplantation (HSCT) from matched sibling donors (MSD) or unrelated donors (UD) is limited and with controversial results. The study aim was to evaluate PT-Cy as GVHD prophylaxis post-HSCT from MSD and UD transplants. We analyzed 423 patients with acute leukemia who received PT-Cy alone or in combination with other immunosuppressive (IS) drugs as GVHD prophylaxis. Seventy-eight patients received PT-Cy alone (group 1); 204 received PT-Cy in combination with one IS drug—cyclosporine-A (CSA) or methotrexate (MTX) or mycophenolate-mofetil (MMF) (group 2), while 141 patients received PT-Cy in combination with two IS drugs—CSA + MTX or CSA + MMF (group 3). Transplants were performed from 2007 to 2015 and median follow-up was 20 months. Results: Probability of overall survival (OS) at 2 years was 50, 52.2, and 62.4%, for the three groups, respectively, p = 0.06. In multivariate analysis, in comparison to PT-Cy alone, the addition of two IS drugs was associated with reduced risk of extensive cGVHD (HR 0.25, p = 0.02). Use of bone marrow (BM) and anti-thymocyte globulin were independently associated with reduced risk of extensive cGVHD. Prognostic factors for non-relapse mortality (NRM) were the addition of two IS drugs to PT-Cy (HR 0.35, p = 0.04), diagnosis of AML, disease status at transplant, and patient CMV serology. Factors associated with increased OS were the use of PT-Cy with two IS drugs (HR 0.49, p = 0.02), AML, and disease status at transplant. Conclusion: For GVHD prophylaxis in MSD and UD HSCT, the addition of IS drugs to PT-Cy enhances its effect and reduces the risk of severe cGVHD, reducing mortality and improving survival. [ABSTRACT FROM AUTHOR]

The author comments on the effect of amino acid substitutions (AASs) at particular peptide positions of class I antigens. The author states that the functional and biologic role of AASs in main positions of the human leukocyte antigen (HLA) class I molecule. He also mentions that the increased risk of graft-versus-host disease (GVHD) was discovered in univariate analysis.

In this article, the author discusses aspects of the superiority of bone marrow (BM) in the unrelated transplantations for patients with aplastic anemia (AA) as it is used as the stem cell source compared with peripheral blood (PB). He notes that PB grafts did increase chronic graft-versus-host disease (cGVHD) which is the cause of the superiority of BM in the HLA identical sibling transplant. He adds that PB grafts are considered as a default stem cell source by international registries.

We studied adults with acute myeloid leukemia (AML) after haploidentical (n=192) and 8/8 HLA-matched unrelated donor (n=1982), transplantation. Data were obtained from the Center for International Blood and Marrow Transplant Research. Haploidentical recipients received calcineurin inhibitor (CNI), mycophenolate and post-transplant cyclophosphamide for graft-versus-host disease (GVHD) prophylaxis; 104 patients received myeloablative and 88, reduced intensity conditioning regimens. Matched unrelated donor transplant recipients received CNI with mycophenolate or methotrexate for GVHD prophylaxis; 1245 patients received myeloablative and 737, reduced intensity conditioning regimens. In the myeloablative setting, day-30 neutrophil recovery was lower after haploidentical compared to matched unrelated donor transplants (90% versus 97%, p=0.02). Corresponding rates after reduced intensity conditioning transplants were 93% and 96%, (p=0.25). In the myeloablative setting, 3-month acute grade 2-4 (16% versus 33%, p<0.0001) and 3-year chronic GVHD (30% versus 53%, p<0.0001) were lower after haploidentical compared to matched unrelated donor transplants. Similar differences were observed after reduced intensity conditioning transplants, 19% versus 28%, (p=0.05) and 34% versus 52%, (p=0.002). Among patients receiving myeloablative regimens, 3-year probabilities of overall survival were 45% (95% CI 36-54) and 50% (95% CI 47-53) after haploidentical and matched unrelated donor transplants (p=0.38). Corresponding rates after reduced intensity conditioning transplants were 46% (95% CI 35-56) and 44% (95% CI 0.40-47) (p=0.71). Although statistical power is limited, these data suggests that survival for patients with AML after haploidentical transplantation with posttransplant cyclophosphamide is comparable with matched unrelated donor transplantation. [ABSTRACT FROM AUTHOR]

Summary: Background: Most allogeneic haematopoietic stem cell transplants now use peripheral blood progenitor cell transplantation (PBPCT) instead of bone-marrow transplantation (BMT). Long-term data on outcome and late effects of PBPCT compared with BMT are scarce. Here we present long-term data from a randomised study comparing PBPCT with BMT. Methods: Between February, 1995, and September, 1999, 329 patients with leukaemia received either PBPCT (n=163) or BMT (n=166) from HLA-identical sibling donors after central randomisation accounting for stratification criteria. Follow-up data were collected via questionnaires from 87% (176 of 202; 84 PBPCT, 92 BMT) patients who survived for more than 3 years (median of 9·3 years) after transplantation. Efficacy analyses included all patients who received treatment. This study is registered with ClinicalTrials.gov, number NCT01020175. Findings: 10-year overall survival was 49·1% for patients who underwent PBPCT and 56·5% for patients who underwent BMT (HR 0·83, 95% CI 0·60–1·15; p=0·27). Leukaemia-free survival was 28·3% with BMT versus 13·0% with PBPCT (0·61, CI 0·32–1·16; p=0·12) for acute lymphoblastic leukaemia; 62·3% with BMT versus 47·1% with PBPCT for acute myeloid leukaemia (0·67, 0·39–1·16; p=0·16); and 40·2% with BMT versus 48·5% with PBPCT for chronic myeloid leukaemia (1·12, 0·73–1·74; p=0·60). More patients developed chronic graft-versus-host disease after PBPCT (n=56, 73%) than after BMT (n=46, 56%; p=0·021), with more frequent involvement of skin, liver, and oral mucosa, and more patients who underwent PBPCT needed immunosuppressive treatment 5 years after transplantation (n=20, 26%) than patients who had BMT (n=10, 12%; p=0·024). Nonetheless, there was no difference in performance status, return to work, incidence of bronchiolitis obliterans, and haematopoietic function between the two groups. 14 cases of secondary malignancies occurred (five after BMT, nine after PBPCT), resulting in a cumulative incidence of 3% and 7% after BMT and PBPCT (p=0·17), respectively. Interpretation: More than 9 years after transplantation, overall and leukaemia-free survival remain similar in patients who underwent BMT and PBPCT. Differences in the incidence of chronic graft-versus-host disease and the duration of immunosuppression exist, but do not affect survival, general health status, or late events. Funding: No external funding was received. [Copyright &y& Elsevier]

• The combination of thiotepa and busulfan fludarabine reduces the risk of relapse in patients with remission acute myeloid leukemia compared with myeloablative busulfan fludarabine. • The effect is independent of donor type and graft-versus-host disease prophylaxis. This is a multicenter retrospective comparison of 2 myeloablative conditioning regimens in 454 patients with acute myeloid leukemia (AML) in remission: busulfan (4 days) and fludarabine (BUFLU) versus thiotepa, busulfan, and fludarabine (TBF). Eligible for this study were patients allografted between January 2008 and December 2018 in 10 transplant centers, with AML in first or second remission: 201 patients received BUFLU, whereas 253 received TBF. The 2 groups (BUFLU and TBF) were comparable for age (P =.13) and adverse AML risk factors (P =.3). The TBF group had more second remissions and more haploidentical grafts. The donor type included HLA-identical siblings, unrelated donors, and family haploidentical donors. The 5-year cumulative incidence of nonrelapse mortality (NRM) was 19% for BUFLU and 22% for TBF (P =.8), and the 5-year cumulative incidence of relapse was 30% and 15%, respectively (P =.0004). The 5-year actuarial survival was 51% for BUFLU and 68% for TBF (P =.002). In a multivariate Cox analysis, after correcting for confounding factors, the use of TBF reduced the risk of relapse compared with BUFLU (P =.03) and the risk of death (P =.03). In a matched pair analysis of 108 BUFLU patients matched with 108 TBF patients, with the exclusion of haploidentical grafts, TBF reduced the risk of relapse (P =.006) and there was a trend for improved survival (P =.07). Superior survival of patients receiving TBF as compared with BUFLU is due to a reduced risk of relapse, with comparable NRM. The survival advantage is independent of donor type and AML risk factors. [ABSTRACT FROM AUTHOR]

We analyzed data relative to cell content in 88 consecutive patients receiving HLA haploidentical bone marrow (BM) transplants with post-transplantation cyclophosphamide (PT-CY). Median age was 54.5 (range, 17–72); diagnoses were acute leukemia (n = 46), lymphoproliferative disorders (n = 24), myelofibrosis (n = 11) and myelodysplastic syndromes (n = 5). Total nucleated cell (TNC) and CD34+, CD3+, CD4+ and CD8+ cell doses were stratified as higher than first, second and third quartile and the dose effect on various clinical outcomes was assessed. Median time to engraftment was 17 days for neutrophils and 24 days for platelets. To receive a dose of TNC ≥3.2 x 106/kg or CD34+ cells ≥2.7 x 106/kg significantly shortened the time to neutrophil and platelet engraftment and reduced the blood product requirements in the 30-day period after transplantation. Overall, TNC and CD34+ cell doses had no effect on acute graft-versus-host disease (GVHD) incidence, whereas patients receiving higher CD3+ and CD8+ cell doses seemed to have less chronic GVHD. No effect on non-relapse mortality, progression-free survival and overall survival was observed at different cell dose thresholds. These data suggest that in HLA haploidentical BM transplant with PT-CY, appropriate cell doses are relevant to the engraftment. The association between low CD3+/CD8+ cells and chronic GVHD deserves further investigation. [ABSTRACT FROM AUTHOR]

Highlights • Allogeneic transplantation is a valid approach for advanced Hodgkin lymphoma. • Pretransplant comorbidity has a great impact on transplant outcomes. • Pretransplant functional imaging analysis predicts post-transplant relapse rate. • Long lasting Hodgkin remissions have been observed in post-transplant relapses. Abstract Disease relapse remains an unmet medical need for patients with Hodgkin lymphoma (HL) receiving an allogeneic hematopoietic cell transplantation (HCT). With the aim of identifying patients at high risk for post-transplant relapse, we retrospectively reviewed 41 HL patients who had received haploidentical (haplo) nonmyeloablative (NMA) HCT with high dose post-transplant cyclophosphamide (PT-Cy) for graft-versus-host (GVHD) prophylaxis. Primary refractory disease, relapse within 6 months from autologous stem cell transplantation, age, pretransplant chemotherapy, HCT comorbidity index (HCT-CI), sex mismatch, tumor burden and pretransplant fluorodeoxyglucose positron emission tomography (FDG-PET) status, assessed by Deauville score, were analyzed as variables influencing outcomes. All but 1 patient engrafted: median time to neutrophil and platelet recovery was 15 (interquartile range, 13 to 23) days and 19 (interquartile range, 12 to 28) days, respectively. Cumulative incidence of severe (grade III to IV) acute graft-versus-host disease (GVHD) and 3-year moderate-severe chronic GVHD was 2.4% and 11.8%, respectively. The 3-year overall (OS), progression free (PFS), and graft relapse-free survival (GRFS) were 75.6%, 43.9%, and 39%, respectively. On multivariate analysis, 3-year OS was significantly worse in patients with HCT-CI ≥3 (hazard ratio [HR], 5.0; 95% confidence interval [CI], 1.1 to 21.8; P =.03). Three-year relapse rate, 3-year PFS, and 3-year GRFS were significantly worse in patients with HCT-CI ≥3 (HR, 3.5; 95% CI, 1.3 to 9.3; P =.01; HR, 3.3; 95% CI, 1.2 to 9.0; P =. 02; and HR, 4.2; 95% CI, 1.7 to 9.9; P =. 001, respectively) and in patients with a Deauville score ≥4 on pretransplant FDG-PET (HR, 4.4; 95% CI, 1.6-12.4; P =. 005, HR, 3.8; 95% CI, 1.5 to 9.7; P =. 005; and 3.2; 95% CI, 1.3 to 7.9; P =. 01, respectively). On univariate analysis, 3-year NRM was significantly worse only in patients with a HCT-CI ≥3 (HR, 17.6; 95% CI, 1.4 to 221.0). Among relapsed or refractory HL patients undergoing haplo NMA HCT with PT-Cy, pretransplant FDG-PET with a Deauville score ≥4 and HCT-CI ≥3 identified patients at high risk of relapse. Moreover, an HCT-CI ≥3 was associated with higher NRM and lower OS. [ABSTRACT FROM AUTHOR]

The current COVID-19 pandemic has placed unprecedented stress on the healthcare system, including HSCT. Several international organizations have created guidelines for managing different aspects of HSCT in the context of the pandemic. Comparing 2019 and 2020, our transplant center performed the same number of transplants. In both periods, transplants were mainly for patients with acute leukemia; thus, the urgency criteria was respected in light of pandemic restraints. Transplants by sibling donors and cord blood units remained the same, while transplants by unrelated donors were increased, in particular from European registries, and transplants by haploidentical donors were decreased. This change was made in light of the necessity of cryopreserving all apheresis products. We decided against cryopreserving bone marrow products due to the greater risk of drastic reduction in CD34 + cell count during the process. For urgent cases with only a haploidentical donor available, we opted for the use of PBSC following stimulation with G-CSF. GvHD prophylaxis was performed with PTCY on days + 3 + 5, cyclosporine with tapering from day + 100, and mycophenolic acid until day + 90 post-HSCT. Post-transplant outcomes such as graft failure, sepsis, and GVHD were not affected by the changes implemented. As a result of logistic difficulties, we halted our Car-T program from the start of the lockdown in March 2020 until September 2020. In accord with international guidelines, we were able to continue our HSCT program in the order to ensure a lifesaving treatment for patients with hematologic diseases for whom this procedure cannot be postponed. ● During the Covid19 pandemic, international organizations produced guidelines for the management of different aspects of HSCT. ● The principal change was the mandatory indication to cryopreserve for all the apheresis products. ● The main indication for transplant was acute leukemia to respect the urgency criteria. ● For urgent patients with only haploidentical donors, we use PBSC after G-CSF stimulation and modify the GVHD prophylaxis. ● We continued HSCT activities in the order to ensure a lifesaving treatment for patients for whom this procedure cannot be postponed [ABSTRACT FROM AUTHOR]

To investigate rates and outcomes of antibiotic de-escalation during pre-engraftment neutropenia in allogeneic hematopoietic stem cell transplantation (HSCT) recipients. 110 consecutive HSCTs performed between January 2013 and March 2014 were analyzed. De-escalation was defined as narrowing the spectrum of antibiotic treatment either within (early) or after 96 hours (late) from starting antibiotics. Discontinuation, considered a form of de-escalation, was defined as stopping antibiotics before engraftment. De-escalation failure was defined as restarting/escalating antibiotics within 96 hours after de-escalation. Predictors of de-escalation were analyzed. Among 102 patients who started antibiotics and were included, 68 (67%) received monotherapy (mainly piperacillin-tazobactam, n = 58), whereas 34 (33%) received combination therapy (mainly meropenem plus glycopeptide, n = 24). Median duration of neutropenia was 17 days. Bloodstream infections (BSIs) were diagnosed in 28 patients (20%). Early de-escalation rate was 25.5% (n = 26) and mostly consisted of reducing the spectrum of β-lactams (n = 11, 42%). In comparison with theoretical scenario of continuing therapy until engraftment, the median savings in terms of antibiotic days were 10 for meropenem, 8 for piperacillin-tazobactam, and 7 for vancomycin. Failure rate of early de-escalation was 15% (4/26). Late de-escalation rate was 30.4% (n = 31) and failure rate 19% (6/31). The rate of de-escalation any time before engraftment was 55.9% (n = 57), including discontinuation in 33 patients (32%). Death at day 60 after HSCT occurred in 3 patients who never underwent de-escalation. Acute myeloid disease and BSIs were independent predictors of early de-escalation. De-escalation, including discontinuation, is feasible and safe in pre-engraftment neutropenia after allogeneic HSCT. [ABSTRACT FROM AUTHOR]

Minimal residual disease (MRD) was monitored by Wilms tumor 1 ( WT1 ) expression in 207 patients with acute myeloid leukemia (AML) after an allogeneic hemopoietic stem cell transplantation (HSCT) as a trigger to initiate pre-emptive immunotherapy (IT) with cyclosporin discontinuation and/or donor lymphocyte infusion. The trigger for IT was WT1 ≥ 180 copies/10 4 Abelson cells in marrow cells in the first group of 122 patients (WT1-180) and ≥ 100 copies in a subsequent group of 85 patients (WT1-100). Forty patients received IT. The cumulative incidence (CI) of relapse was 76% in WT1-180 (n = 17) versus 29% in WT1-100 patients (n = 23) receiving IT ( P = .006); the leukemia-free survival from MRD positivity was 23% versus 74%, respectively ( P = .003). We then looked at the entire AML patient population (n = 207). WT1-180 and WT1-100 patients were comparable for disease phase and age. The overall 4-year CI of transplantation-related mortality was 13% in both groups; the CI of leukemia relapse was 38% in the WT1-180 and 28% in the WT1-100 patients ( P = .05) and leukemia-free survival was 56% versus 48%, respectively ( P = .07). In conclusion, we suggests that WT1-based pre-emptive immunotherapy is feasible in patients with undergoing an allogeneic HSCT. The protective effect on relapse is greater when IT is triggered at lower levels of WT1. [ABSTRACT FROM AUTHOR]

Mechanisms of hematopoietic reconstitution after bone marrow (BM) transplantation remain largely unknown. We applied a computational quantification software application to hybrid 18F-fluorodeoxyglucose positron emission tomography (PET)/computed tomography (CT) images to assess activity and distribution of the hematopoietic system throughout the whole skeleton of recently transplanted patients. Thirty-four patients underwent PET/CT 30 days after either adult stem cell transplantation (allogeneic cell transplantation [ACT]; n = 18) or cord blood transplantation (CBT; n = 16). Our software automatically recognized compact bone volume and trabecular bone volume (IBV) in CT slices. Within IBV, coregistered PET data were extracted to identify the active BM (ABM) from the inactive tissue. Patients were compared with 34 matched controls chosen among a published normalcy database. Whole body ABM increased in ACT and CBT when compared with controls (12.4 ± 3 and 12.8 ± 6.8 vs 8.1 ± 2.6 mL/kg of ideal body weight [IBW], P< .001). In long bones, ABM increased three-and sixfold in CBT and ACT, respectively, compared with controls (0.9 ± 0.9 and 1.7 ± 2.5 vs 0.3 ± 0.3 mL/kg IBW, P< .01). These data document an unexpected distribution of transplanted BM into previously abandoned BM sites. [ABSTRACT FROM AUTHOR]

Although transplant practices have changed over the last decades, no information is available on trends in incidence and outcome of chronic graft-versus-host disease (cGVHD) over time. This study used the central database of the Center for International Blood and Marrow Transplant Research (CIBMTR) to describe time trends for cGVHD incidence, nonrelapse mortality, and risk factors for cGVHD. The 12-year period was divided into 3 intervals, 1995 to 1999, 2000 to 2003, and 2004 to 2007, and included 26,563 patients with acute leukemia, chronic myeloid leukemia, and myelodysplastic syndrome. Multivariate analysis showed an increased incidence of cGVHD in more recent years (odds ratio = 1.19, P < .0001), and this trend was still seen when adjusting for donor type, graft type, or conditioning intensity. In patients with cGVHD, nonrelapse mortality has decreased over time, but at 5 years there were no significant differences among different time periods. Risk factors for cGVHD were in line with previous studies. This is the first comprehensive characterization of the trends in cGVHD incidence and underscores the mounting need for addressing this major late complication of transplantation in future research. [ABSTRACT FROM AUTHOR]

We studied 459 consecutive patients with hematologic malignancies, median age 44 years (range, 15 to 71 years), who underwent transplantation with grafts from identical sibling donors (SIB; n = 176), matched unrelated donors (MUD; n = 43), mismatched unrelated donors (mmUD; n = 43), unrelated cord blood (UCB; n = 105) or HLA-haploidentical family donors (HAPLO; n = 92). Graft-versus-host disease (GVHD) prophylaxis consisted of cyclosporine and methotrexate in the SIB recipients; antithymocyte globulin for the MUD, mmUD, and UCB recipients; and post-transplantation cyclophosphamide, cyclosporine, and mycophenolate in the HAPLO recipients. Conditioning regimens were mostly myeloablative (69%). Advanced disease phase was more frequent, but not significantly so, in the HAPLO and mmUD groups ( P = .08). Acute GVHD grade II-IV was significantly less frequent in the HAPLO, UCB, and MUD groups (14% to 21%) compared with the SIB (31%) and mmUD (42%) groups ( P < .001), and there was a trend toward less moderate-severe chronic GVHD in the HAPLO and UCB groups ( P = .053). The proportion of patients off cyclosporine at 1 year ranged from 55% for the SIB group to 81% for the HAPLO group ( P < .001). Transplantation-related mortality at 2 years was lower in the HAPLO and SIB groups (18% to 24%) compared with the MUD, mmUD, and UCB groups (33% to 35%; P = .10). Relapse rate was comparable in the 5 groups ( P = .80). The 4-year actuarial survival was 45% in the SIB group, 43% in the MUD group, 40% in the mmUD group, 34% in the UCB group, and 52% in the HAPLO group ( P = .10). In multivariate analysis, advanced disease was a negative predictor of survival (hazard ratio [HR], 2.4; P < .0001), together with a diagnosis of acute leukemia (HR, 1.8; P = .0001); HAPLO grafts were comparable to SIB ( P = .80), whereas UCB had inferior survival ( P = .03). In conclusion, unmanipulated haploidentical family donor transplants are an additional option for patients lacking a matched sibling donor. [ABSTRACT FROM AUTHOR]

Poor graft function (PGF) is characterized by pancytopenia and a hypoplastic marrow, with complete donor chimerism, usually without severe graft-versus-host disease (GVHD). We report 41 patients with PGF, treated with granulocyte colony-stimulating factor-mobilized CD34 selected cells, at a median interval from transplant of 140 days, without conditioning and without GVHD prophylaxis. Donors were HLA matched siblings (n = 12), unrelated donors (n = 18), or mismatched family members (n = 11). The median number of infused CD34+ cells was 3.4 × 106/kg. The rate of trilineage recovery was 75%: 83% for HLA matched siblings and 72% for unrelated and mismatched family members (P = .3). The cumulative incidence of acute grade II GVHD was 15%, and no patient developed de novo chronic GVHD. The actuarial 3-year survival is 63%: 76% and 25% for patients with or without trilineage recovery. These data confirm the role of CD34+ selected cells from the same donor in the treatment of PGF and warrant the request for a second donation also when the donor is unrelated. [ABSTRACT FROM AUTHOR]

Although allogeneic hematopoietic stem cell transplantation (HSCT) remains the only curative treatment for patients with Fanconi anemia (FA), published series mostly refer to single-center experience with limited numbers of patients. We analyzed results in 795 patients with FA who underwent first HSCT between May 1972 and January 2010. With a 6-year median follow-up, overall survival was 49% at 20 years (95% confidence interval, 38-65 years). Better outcome was observed for patients transplanted before the age of 10 years, before clonal evolution (ie, myelodysplastic syndrome or acute myeloid leukemia), from a matched family donor, after a conditioning regimen without irradiation, the latter including fludarabine. Chronic graft-versus-host disease and secondary malignancy were deleterious when considered as time-dependent covariates. Age more than 10 years at time of HSCT, clonal evolution as an indication for transplantation, peripheral blood as source of stem cells, and chronic graft-versus-host disease were found to be independently associated with the risk for secondary malignancy. Changes in transplant protocols have significantly improved the outcome of patients with FA, who should be transplanted at a young age, with bone marrow as the source of stem cells. [ABSTRACT FROM AUTHOR]

Abstract: Fifty patients with high-risk hematologic malignancies, underwent an unmanipulated haploidentical bone marrow transplantation (BMT), followed by posttransplantation high-dose cyclophosphamide (PT-CY): the myeloablative (MA) conditioning consisted of thiotepa, busulfan, fludarabine (n = 35), or total body irradiation (TBI), fludarabine (n = 15). The median age was 42 years (range, 18-66 years); 23 patients were in remission, 27 had active disease, and 10 patients were receiving a second allograft. Graft-versus-host disease (GVHD) prophylaxis consisted in PT-CY on day +3 and +5, cyclosporine (from day 0), and mycophenolate (from day +1). Three patients died before engraftment, and 2 patients had autologous recovery: 45 patients (90%) had full-donor chimerism on day +30. The median day for neutrophil engraftment was day +18 (range, 13-30 days). The cumulative incidence of grade II-III acute GVHD (aGVHD) was 12%, and of moderate chronic GVHD (cGVHD) 10%. With a median follow-up for surviving patients of 333 days (range, 149-623 days), the cumulative incidence of transplantation-related mortality (TRM) was 18%, and the rate of relapse was 26%. The actuarial 22-month disease-free survival (DFS) rate was 68% for patients in remission and 37% for patients with active disease (P < .001). Causes of death were pneumonia (n = 3), hemorrhage (n = 3), sepsis (n = 3), and relapse (n = 7). In conclusion, an MA conditioning regimen followed by haploidentical BMT with PT-CY results in a low risk of aGVHD and cGVHD and encouraging rates of TRM and DFS. [Copyright &y& Elsevier]

Abstract: We have reported a lower incidence of acute graft-versus-host disease (aGVHD) with a novel conditioning regimen using low-dose rabbit antithymocyte globulin (ATG; Thymoglobulin [TG]) with fludarabine and intravenous busulfan (FluBuTG). To assess further this single-center experience, we performed a retrospective matched-pair analysis comparing outcomes of adult patients transplanted using the FluBuTG conditioning regimen with matched controls from patients reported to the CIBMTR receiving a first allogeneic hematopoietic stem cell transplant (HCT) after standard oral busulfan and cyclophosphamide (BuCy). One hundred twenty cases and 215 matched controls were available for comparison. Patients receiving FluBuTG had significantly less treatment related mortality (TRM; 12% versus 34%, P < .001) and grades II-IV aGVHD (15% versus 34%, P < .001) compared to BuCy patients. The risk of relapse was higher in the FluBuTG patients (42% versus 20%, P < .001). The risks of chronic GVHD (cGVHD) and disease free survival (DFS) were similar in the cases and controls. These results suggest that the novel regimen FluBuTG decreases the risk of aGVHD and TRM after HLA-identical sibling HSCT, but is associated with an increased risk of relapse, resulting in similar DFS. Whether these conditioning regimens may be more suitable for specific patient populations based on relapse risk requires testing in prospective randomized trials. [Copyright &y& Elsevier]

The article presents a study to determine if mesenchymal stem cells could ameliorate severe graft-versus-host disease (GVHD) after haemopoietic-stem-cell transplantation. GVHD patients treated with mesenchymal stem cells were observed for adverse effects for 60 months. Patients were found to have a higher overall survival rate 2 years after the stem cell treatment. The findings suggest that mesenchymal stem cell infusion may be an effective treatment for patients with steroid-resistant, acute GVHD.

Abstract: Mesenchymal stem cells (MSCs) are found in a variety of tissues, including human bone marrow; secrete hematopoietic cytokines; support hematopoietic progenitors in vitro; and possess potent immunosuppressive properties. We hypothesized that cotransplantation of culture-expanded MSCs and hematopoietic stem cells (HSCs) from HLA-identical sibling donors after myeloablative therapy could facilitate engraftment and lessen graft-versus-host disease (GVHD); however, the safety and feasibility of this approach needed to be established. In an open-label, multicenter trial, we coadministered culture-expanded MSCs with HLA-identical sibling-matched HSCs in hematologic malignancy patients. Patients received either bone marrow or peripheral blood stem cells as the HSC source. Patients received 1 of 4 study-specified transplant conditioning regimens and methotrexate (days 1, 3, and 6) and cyclosporine as GVHD prophylaxis. On day 0, patients were given culture-expanded MSCs intravenously (1.0¿5.0 × 106/kg) 4 hours before infusion of either bone marrow or peripheral blood stem cells. Forty-six patients (median age, 44.5 years; range, 19¿61 years) received MSCs and HLA-matched sibling allografts. MSC infusions were well tolerated, without any infusion-related adverse events. The median times to neutrophil (absolute neutrophil count ¿0.500 × 109/L) and platelet (platelet count ¿20 × 109/L) engraftment were 14.0 days (range, 11.0¿26.0 days) and 20 days (range, 15.0¿36.0 days), respectively. Grade II to IV acute GVHD was observed in 13 (28%) of 46 patients. Chronic GVHD was observed in 22 (61%) of 36 patients who survived at least 90 days; it was extensive in 8 patients. Eleven patients (24%) experienced relapse at a median time to progression of 213.5 days (range, 14¿688 days). The probability of patients attaining disease- or progression-free survival at 2 years after MSC infusion was 53%. Cotransplantation of HLA-identical sibling culture-expanded MSCs with an HLA-identical sibling HSC transplant is feasible and seems to be safe, without immediate infusional or late MSC-associated toxicities. The optimal MSC dose and frequency of administration to prevent or treat GVHD during allogeneic HSC transplantation should be evaluated further in phase II clinical trials. [Copyright &y& Elsevier]