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The aim of our study was to evaluate the feasibility and the safety of the use of peripherally inserted central catheters (PICCs) during autologous peripheral blood stem cell transplantation. Sixty PICCs were inserted in 57 patients (23 females and 34 males; mean age 48, range 19-68 years) and remained in place for an overall period of 1,276 days. All PICCs were positioned by a team of specifically trained physicians and nurses and utilized by specifically trained nurses of our hematology unit. No major insertion-related complications were observed; the only complication during insertion was one local hematoma (1.6 %) due to accidental arterial puncture. Late complications were accidental catheter removal (5 %, 2.3 per 1,000 PICC days), symptomatic catheter-related venous thrombosis (5 %, 2.3 per 1,000 PICC days), and catheter-related bloodstream infection (CRBSI; 3.3 %, 1.5 CRBSI per 1,000 PICC days). The reasons for catheter removal were completion of therapy (42 patients, 70 %), fever of unknown origin (9 patients, 15 %), catheter-related thrombosis (2 patients, 3.3 %), CRBSI (2 patients, 3.3 %), accidental removal (3 patients, 5 %), lumen occlusion (1 patient, 1.6 %), positive culture from peripheral blood (1 patient, 1.6 %), and death (1 patient, 1.6 %). Our data suggest that PICCs are a safe and effective alternative to conventional central venous catheters even in patients particularly prone to infective and hemorrhagic complications such as patients receiving autologous stem cell transplantation.

Epstein-Barr Virus (EBV) reactivation and EBV-related post-transplant lymphoproliferative disease (PTLD) have emerged as a severe complication after stem cell transplantation (SCT). We prospectively evaluated 104 consecutive patients receiving SCT either autologous or allogeneic. Fifty-two patients (50%) presented EBV DNA-emia and five of them developed PTLD proven or probable. PTLD rate was 9.6% among patients with EBV DNA-emia. One patient developed PTLD without EBV DNA-emia (0.96%). Overall PTLD incidence was 5.7%. No PTLD developed after autologous SCT. EBV DNA-emia was significantly more frequent after allogeneic than autologous SCT (60.7% vs 17.4%, p = 0.0002). At EBV reactivation, serum protein electrophoresis and immunofixation were assessed. Global incidence of γ-peak after allogeneic SCT with EBV reactivation was 65.3% (32/49 patients) and monoclonal gammopathy (MG) was identified in 23/28 evaluable patients (82%). All patients with PTLD developed γ-peak and in five of them MG was identified. MG is consistently associated with EBV DNA-emia and may help identification of progression to PTLD after allogeneic SCT.

Objective: To evaluate HRT compliance and efficacy in the treatment of symptomatic ovarian failure in pre-menopausal women after stem cell transplantation (SCT) for malignancies., Methods: Thirty-one females were selected and prospectively followed in a university bone marrow transplantation unit and gynecologic outpatient clinic in a university teaching hospital. The patients received regular gynecological examinations, hormonal assessment every 6 months including plasma levels of luteinizing hormone (LH), follicle stimulating hormone (FSH), 17-beta estradiol (E2), and transvaginal pelvic ultrasonography, mammography, and computerized bone mineralometry every 12 months. Self-assessment form of menopausal symptoms perception was filled in by all patients before HRT and during the observation period., Results: All patients developed gonadal failure after SCT. The menopausal symptoms more frequently reported were: vasomotor (90%), muscleskeletal symptoms (61%), vulvo-vaginal atrophy (54%), and mood changes (54%). Fifteen premenopausal women out of 31 (51.6%) received systemic HRT on the basis of age (<45 years), absence of medical contraindication or subjective refusal, and complete remission of underlying malignancies post-SCT. The remaining patients (48.4%) did not receive HRT mainly for patient's refusal (29%), relapse of malignancy (13%) or liver toxicity (9.6%). HRT was effective in HRT treated patients promptly relieving unpleasant symptoms of gonadal failure. HRT was tolerated without minimal complications or serious side effects., Conclusions: Dramatic improvement in menopausal symptoms was observed in women on HRT although treatment was feasible only in nearly half of the patients. HRT alleviates unnecessary discomfort and improves the well-being of female patients post-transplant also by preventing menopause related complications. Feasibility and patients' compliance of HRT should be carefully evaluated in long-term survivors after stem cell transplantation.

Introduction: Donor-specific antibodies (DSAs) correspond to anti-HLA antibodies of the recipient that are specifically directed to a mismatched antigen of the donor. In the setting of solid organ transplantation DSAs are associated with rejection. Their role is still debated in allogeneic cell transplantation. International guidelines recommend testing patients for DSA before transplant, and if possible, choosing a donor with negative screening. Methods: We collected clinical data of 236 recipients of alloSCT, performed at our institution from March 2019 to October 2023, to evaluate their impact on engraftment. Serum from all patients was tested for DSA. Results: 186 patients (79%) achieved sustained myeloid engraftment within day 30 post alloSCT. Thirty-two out 236 (13%) patients engrafted after day 30 post alloSCT. The median times to neutrophil engraftment and platelet engraftment were respectively 21 days (range 11-121 days) and 19 days (range 10-203 days). Fourteen out 236 patients (6%) experienced PrGF. .Twenty-nine patients (12 %) were DSA-positive. Among 29 patients with DSA positivity, 17 had a haploidentical donor and 12 had a UD donor. DSA positivity directly correlates respectively with neutrophil and platelets engraftment failure at 30 days after alloSCT (p=0.01 and p= 0.0004). Univariate Cox analysis showed that factors, including DSAs positivity, disease type, disease status, donor type, conditioning regimen, patient's age, and CD34+ were correlated with neutrophil and platelet engraftment failure at 30 days after alloSCT. Younger patients with DSA negativity, with acute leukemia, in complete response at the time of transplant, who received a higher dose of CD34+ cells from a sibling donor after a myeloablative conditioning regimen, have a reduced risk of neutrophil and platelet engraftment failure at day +30 post alloSCT.Multivariate analysis confirmed the impact of the presence of DSA only for platelet engraftment, confirming the role of type and status disease, donor type, recipient age, and CD34+ cells infused on engraftment. DSA presence has no impact on TRM, DFS, and OS. Discussion: PrGF has a multifactorial pathogenesis, where DSA is not the only player, but its impact could vary depending on the transplant platform. Thus patient screening may be helpful to choose the best donor and transplant strategy. [ABSTRACT FROM AUTHOR]

Background: Pure red cell aplasia (PRCA) is a possible complication after allogeneic hematopoietic stem cell transplantation (HSCT) with major ABO incompatibility. Patients experience delayed engraftment of the erythroid series, with prolonged transfusion-dependent anemia and iron overload. Methods: We performed a revision of the most recent literature about post-HSCT PRCA treatment procedures. Moreover, we conducted a retrospective study, over the last 13-years, which included all consecutive major ABO mismatched HSCT performed in our unit, with the aim to assess PRCA incidence, risk factors, and response to different treatments. Overall, 194 patients received a major ABO mismatched transplant from 2010 to 2022. For each patient, data about demographic and transplant characteristics, engraftment, blood transfusion, and possible treatment received were collected. Results: The literature review returned 23 eligible papers on PRCA treatment, with high success rate using plasma-exchange (PEX) and immunoadsorption procedures, daratumumab, and eltrombopag. Our study identified a total of 24 cases of PRCA. Among risk factors for PRCA development, we have found older recipient age (p=0.01), high pre-HSCT IgG and IgM IHA titer (p<0.0001), major rather than bidirectional ABO incompatibility (p=0.02), low T CD8 lymphocyte count in the graft (p=0.006), relative donor (p=0.02) and bone marrow as stem cell source (p=0.002). However, multivariate analysis confirmed only pre-HSCT IgG IHA titer as the unique risk factor for PRCA occurrence. The optimal cut-off value of pre-HSCT IgG IHA for PRCA development, resulted to be 1/64, with a 100% sensitivity and 68.8% specificity (p<0.0001). All patients with PRCA had received rhEPO and transfusion support and 20 patients received additional treatments like PEX, rituximab, and more recently daratumumab. Comprehensively, PEX and rituximab obtained a response in half of the cases, at a variable time, while the few cases of patients we treated with daratumumab suggest promising results. The overall response rate in our cohort was 75%, with significantly better survival (94.4% vs. 16.7%) and lower transplant-related mortality (6.3% vs. 80%) for PRCA responders. Conclusions: Standardized guidelines on when and how to treat PRCA are necessary because the current treatment is controversial among centers. [ABSTRACT FROM AUTHOR]

Introduction: Indications for HSCT are increasing worldwide, paralleled by a growing demand for donors of therapeutic cells. Methods: Herein, we report our real-world experience of adult HPC donor assessment during a 5-year study period (2018-2023): we have retrospectively revised data of 455 potential related stem cell donors, consecutively evaluated at our center. Donor medical history was assessed by a questionnaire and an interview with a trained physician experienced in donation procedures to evaluate donor fitness and medical history. Pre-existing health disorders were fully investigated. Behavioral risk factors for communicable infectious diseases were also routinely explored. Results and discussion: Overall, 351 donors were finally assessed as eligible for HPC donation, and 233 underwent stem cell collection, 158 through apheresis from mobilized peripheral blood, and 75 through bone marrow harvest. Among them, 27 donors were selected despite the presence of pre-existing health conditions, which would be potential exclusion criteria for unrelated donors: 16 suffered from well-controlled cardiovascular diseases (CVD) and 11 from allergic diathesis. Most of the selected donors with pre-existing disorders were candidates for apheresis HPC collection (21, 77.8%), while only six (22.2%) underwent BM harvest. We then analyzed the data relative to the corresponding 233 allogeneic HSCT to explore if the presence of pre-existing diseases in the donors could show any association with transplant characteristics. Transplants from CVD and allergy donors showed no significant disparities in comparison with those from healthy donors. A significant difference emerged regarding the disease severity, with a higher proportion of patients with high/very high disease risk index (DRI) among those receiving grafts from CVD donors (68.7% in transplants from CVD donors versus 36.0% in transplants from healthy donors, p=0.005). Multivariate analysis confirmed that high/very high DRI patients had an increased probability of receiving donations from CVD donors (OR, 4.89; 95%CI, 1.15-20.86; p=0.031). Among donors with well-controlled pre-existing conditions, no adverse events were recorded during stem cell collection or at follow-up. Our results suggest that in patients at high risk for relapse requiring a prompt allogeneic transplant, a familiar donor might be accepted for HPC apheresis donation on less strict criteria than unrelated donors, without risk for both donor and patient. [ABSTRACT FROM AUTHOR]

Introduction: Extracorporal Photophoresis (ECP) is in clinical use for steroidrefractory and steroid-dependent acute GVHD (SR-aGVHD). Based on recent Phase-III study results, ruxolitinib has become the new standard of care for SRaGVHD. Our aim was to collect comparative data between ruxolitinib and ECP in SR-aGVHD in order to improve the evidence base for clinical decision making. Methods: We asked EBMT centers if they were willing to participate in this study by completing a data form (Med-C) with detailed information on GVHD grading, -therapy, -dosing, -response and complications for each included patient. Results: 31 centers responded positively (14%) and we included all patients receiving alloSCT between 1/2017-7/2019 and treated with ECP or ruxolitinib for SR-aGVHD grades II-IV from these centers. We identified 53 and 40 patients with grades II-IV SR-aGVHD who were treated with ECP and ruxolitinib, respectively. We performed multivariate analyses adjusted on grading and type of SR-aGVHD (steroid dependent vs. refractory). At day+90 after initiation of treatment for SR-aGVHD we found no statistically significant differences in overall response. The odds ratio in the ruxolitinib group to achieve overall response vs. the ECP group was 1.13 (95% CI = [0.41; 3.22], p = 0.81). In line, we detected no statistically significant differences in overall survival, progressionfree survival, non-relapse mortality and relapse incidence. Discussion: The clinical significance is limited by the retrospective study design and the current data can’t replace prospective studies on ECP in SR-aGVHD. However, the present results contribute to the accumulating evidence on ECP as an effective treatment option in SR-aGVHD. [ABSTRACT FROM AUTHOR]

Microbiota changes during allogeneic hematopoietic stem cell transplantation has several known causes: conditioning chemotherapy and radiation, broad-spectrum antibiotic administration, modification in nutrition status and diet, and graft-versus-host disease. This article aims to review the current knowledge about the close link between microbiota and allogeneic stem cell transplantation setting. The PubMed search engine was used to perform this review. We analyzed data on microbiota dysbiosis related to the above-mentioned affecting factors. We also looked at treatments aimed at modifying gut dysbiosis and applications of fecal microbiota transplantation in the allogeneic stem cell transplant field, with particular interest in fecal microbiota transplantation for graft-versus-host disease (GvHD), multidrug-resistant and clostridium difficile infections, and microbiota restoration after chemotherapy and antibiotic therapy. [ABSTRACT FROM AUTHOR]

This letter published in the European Journal of Clinical Microbiology & Infectious Diseases discusses a case of a 49-year-old woman who experienced late-onset HBV reactivation after hematopoietic stem cell transplantation (HSCT), despite being on long-term prophylaxis with lamivudine. The patient had acute myeloid leukemia and received a bone marrow stem cell transplant from her haploidentical sister. The letter highlights the risk factors for HBV reactivation during HSCT and emphasizes the importance of close monitoring and appropriate antiviral therapy. The article also discusses the risk of HBV reactivation after HSCT, even in patients without traditional risk factors, and recommends routine monitoring and continued prophylactic therapy to prevent HBV reactivation. [Extracted from the article]

Patient N. 4 had moderate COVID-19 disease four months before cell therapy, requiring hospital admission and oxygen support because of interstitial pneumonia. Severe COVID-19 disease and COVID-19-related mortality were registered in 39% and 41% of patients, respectively. Starting from February 2021, the distribution of monoclonal antibody (MoA) casirivimab/imdevimab was authorized in Italy for the treatment of mild to moderate COVID-19 disease in patients at high risk for developing severe illness. COVID-19 infection has affected hematologic patients more severely than general population, probably due to underlying impaired immunity response, active chemotherapy and immunosuppressive treatment. [Extracted from the article]

Mixed-phenotype acute leukemia (MPAL) is a rare disease. Treatment is often similar to that of acute lymphoblastic leukemia (ALL), but the outcome in adults and the role of allogeneic stem cell transplantation (AlloSCT) are not well defined. We report on 77 adult patients diagnosed with MPAL over the last 10 years and treated with a curative intent. Median age was 49 years; 7.6% of cases had a BCR::ABL1 rearrangement. Thirty patients (39%) were treated with an acute myeloid leukemia (AML)–like induction and 47 (61%) with an ALL-like scheme. The complete remission (CR) rate was 67.6% and an ALL-like therapy was associated with a better CR rate (P = 0.048). The median OS was 41.9 months; age ≤ 60 years was associated with a better OS (67 vs 26 months, P = 0.014). An AlloSCT was performed in 50 patients (65%). The 5-year OS of transplanted patients was 54%. The OS post-AlloSCT was better in patients who were minimal residual disease (MRD)-negative prior to transplant (75.8% vs 45.2%, P = 0.06). This study shows that MPAL patients respond better to an ALL-like induction therapy; that consolidation therapy should include, whenever possible, an AlloSCT and that MRD negativity should be a primary endpoint of treatment. [ABSTRACT FROM AUTHOR]

Background: In the last decade, many steps forward have been made in acute myeloid leukemia prognostic stratification, adding next-generation sequencing techniques to the conventional molecular assays. This resulted in the revision of the current risk classification and the introduction of new target therapies. Aims and methods: We wanted to evaluate the prognostic impact of acute myeloid leukemia (AML) mutational pattern on relapse occurrence and survival after allogeneic stem cell transplantation. A specific next-generation sequencing (NGS) panel containing 26 genes was designed for the study. Ninety-six patients studied with NGS at diagnosis were included and retrospectively studied for post-transplant outcomes. Results: Only eight patients did not show any mutations. Multivariate Cox regression revealed FLT3 (HR, 3.36; p=0.02), NRAS (HR, 4.78; p=0.01), TP53 (HR, 4.34; p=0.03), and WT1 (HR 5.97; p=0.005) mutations as predictive variables for relapse occurrence after transplantation. Other independent variables for relapse recurrence were donor age (HR, 0.97; p=0.04), the presence of an adverse cytogenetic risk at diagnosis (HR, 3.03; p=0.04), and the obtainment of complete remission of the disease before transplantation (HR, 0.23; p=0.001). Overall survival appeared to be affected only by grade 2--4 acute GvHD occurrence (HR, 2.29; p=0.05) and relapse occurrence (HR, 4.33; p=0.0001) in multivariate analysis. Conclusions: The small number of patients and the retrospective design of the study might affect the resonance of our data. Although results on TP53, FLT3, and WT1 were comparable to previous reports, the interesting data on NRAS deserve attention. [ABSTRACT FROM AUTHOR]

COVID-19 disease has a strong impact on hematological patients; those receiving autologous hematopoietic stem cell transplantation (aHSCT) represent a particularly vulnerable group, in which the effectiveness of vaccination is very variable. Chiarucci et al. showed that patients affected by non-Hodgkin lymphoma (NHL) and treated with rituximab experienced a lower rate of immunization against SARS-CoV-2 (54%), as well as significantly lower IgG antibody titers. In our multicenter retrospective observational study, we included 82 patients who underwent aHSCT, divided into two groups: 58 patients vaccinated after aHSCT (group A) and 24 vaccinated before getting transplantation (group B). In group A, 39 (67%) patients had positive serology, and the rate of positivity increased with time after aHSCT. In the subgroup of patients with NHL, the administration of rituximab predicted negative serology, particularly when administered in the 6 months before vaccination (13% response rate). Patients affected by plasma cells had a higher rate of positivity (83% overall), independently of the time to aHSCT. In group B, no patient who initially showed positive serology became negative after transplantation, so the aHSCT did not affect the response to the vaccination. Our study confirmed the role of rituximab as a negative predictor of response to SARS-CoV-2 vaccination, whereas the conditioning and transplantation procedure itself seemed to be less important. [ABSTRACT FROM AUTHOR]

The aim of this study was to evaluate the role of WT1 expression after allogeneic stem cell transplantation (alloHSCT) in patients with acute myeloid leukemia (AML). We studied WT1 expression in bone marrow cells from 50 patients in complete remission on day +60 after transplant. WT1 was assessed on unfractionated bone marrow mononuclear cells (MNC) and on CD34+ selected cells (CD34+). A ROC curve analysis identified 800 WT1 copies on CD34+ selected cells, as the best cut-off predicting relapse (AUC 0.842, p=0.0006, 85.7% sensitivity and 81.6% specificity) and 100 copies in MNC (AUC 0.819, p=0.007, 83.3% sensitivity and 88.2% specificity). Using the 800 WT1 copy cut off in CD34+ cells, the 2 year cumulative incidence of relapse was 12% vs 38% (p=0.005), and 2 year survival 88% vs 55% (p=0.02). Using the 100 WT1 copy cut off in unfractionated MNC, the 2 year cumulative incidence of relapse 13% vs 44% (p=0.01) and the 2 year survival 88% vs 55% (p=0.08). In a multivariate Cox analysis WT1 expression in CD34 cells proved to highly predictive of relapse (p=0.004); also WT1 expression on unfractionated cells predicted relapse (p=0.03). In conclusion, day-60 WT1 expression after allogeneic HSCT is a significant predictor of relapse, particularly when tested on CD34+ selected bone marrow cells. [ABSTRACT FROM AUTHOR]

Autologous stem cell transplantation (ASCT) is a good option in fit young patients affected by POEMS syndrome. Few data are published on how to treat these patients in case of relapse. In this paper we described our two patients who underwent a second ASCT. From our experience, we can confirm that a second transplant is a real treatment option with good results and limited side effects. It provided excellent response and long-term disease-free survival in POEMS patients who relapsed after a first transplant, including late relapses. [ABSTRACT FROM AUTHOR]

Purpose: Prevention of chemotherapy-induced nausea and vomiting (CINV) is particularly challenging for patients receiving highly emetogenic preparative regimens before autologous stem cell transplantation (ASCT) due to the daily and continuous emetogenic stimulus of the multiple day chemotherapy. While studies have shown effective prevention of CINV during the conditioning phase with NK1 receptor antagonist (NK1RA)-containing regimens, there have been no studies evaluating antiemetic use during chemomobilization prior to ASCT. Methods: This multicenter, open-label, phase IIa study evaluated the efficacy of every-other-day dosing of NEPA administered during chemomobilization in patients with relapsed-refractory aggressive non-Hodgkin's lymphoma. Eighty-one patients participated. Results: Response rates were 77.8% for complete response (no emesis and no rescue use), 72.8% for complete control (complete response and no more than mild nausea), 86.4% for no emesis, and 82.7% for no rescue use during the overall phase (duration of chemomobilization through 48 h after). NEPA was well tolerated with no treatment-related adverse events reported. Conclusion: NEPA, administered with a simplified every-other-day schedule, show to be very effective in preventing CINV in patients at high risk of CINV undergoing to chemomobilization of hematopoietic stem cells prior to ASCT. [ABSTRACT FROM AUTHOR]

BACKGROUND: The use of haploidentical hematopoietic cell transplantation (haplo‐HCT) with posttransplantation cyclophosphamide prophylaxis is gaining traction in patients with acute lymphoblastic leukemia (ALL). METHODS: The Acute Leukemia Working Party/European Society for Blood and Marrow Transplantation registry was used to evaluate the outcomes of adult patients with ALL who underwent haplo‐HCT during 2011 through 2015 and compared them with the outcomes of those who underwent transplantation during 2016 through 2018. RESULTS: The analysis consisted of 195 patients, including 79 who underwent transplantation during 2011 through 2015 and 116 who underwent transplantation during 2016 through 2018. Overall, the 2‐year leukemia‐free survival and relapse incidence rates were 56.5% and 21%, respectively. The 100‐day incidence of grade 2 through 4 acute graft‐vs‐host disease (GVHD) was 34.5%. The rates of nonrelapse mortality (NRM) and overall survival (OS) were 22.5% and 64.7%, respectively. Patients who underwent transplantation during 2016 through 2018 experienced improved rates of leukemia‐free survival (64.9% vs 47.3%; P =.019) and OS (75.5% vs 53.5%; P =.006). Patients who underwent transplantation during 2016 through 2018 developed more grade 2 through 4 acute GVHD (42% vs 26.4%; P =.047). The incidence of relapse, GVHD‐free/relapse‐free survival, grade 3 and 4 acute GVHD, chronic GVHD, and extensive chronic GVHD did not differ significantly between groups. In multivariate analysis, more recently transplanted patients had a significantly reduced risk of NRM (hazard ratio, 0.44; 95% CI, 0.22‐0.89; P =.022) and improved OS (hazard ratio, 0.47; 95% CI, 0.26‐0.86; P =.014). A comparable analysis of patients who had acute myeloid leukemia during the same timeframes did not reveal any statistically significant differences in any outcomes. CONCLUSIONS: The outcome of adult patients with ALL who receive posttransplant cyclophosphamide has improved over time, with an impressive 2‐year OS of 75% and, most recently, an NRM rate of only 17%. In patients with acute lymphocytic leukemia who undergo haploidentical transplantation with posttransplantation cyclophosphamide prophylaxis, significant improvements in leukemia‐free survival and survival are observed in more recently transplanted patients. A nonrelapse mortality rate of 17% is reported in recently transplanted patients with acute lymphocytic leukemia who receive posttransplantation cyclophosphamide prophylaxis. [ABSTRACT FROM AUTHOR]

Background: The coronavirus disease 2019 (COVID-19) pandemic has deeply modified the complex logistical process underlying allogeneic hematopoietic stem cell transplant practices. Aim: In light of these changes, the authors compared data relative to allogeneic transplants carried out from 2018 at their center before (n = 167) and during the pandemic (n = 45). Methods: The authors examined patient characteristics, donor and graft types, cell doses and main transplant outcomes. Moreover, the authors evaluated the rise of costs attributable to additional COVID-19-related procedures as well as the risk of adverse events these procedures conveyed to grafts or recipients. Results: Overall, the number of transplants did not decrease during the pandemic, whereas patients at high relapse risk were prioritized. Transplants were mainly from matched unrelated donors, with a significant decrease in haploidentical related donors. Moreover, the use of bone marrow as a graft for haploidentical transplant was almost abandoned. Cryopreservation was introduced for all related and unrelated apheresis products, with a median storage time of 20 days. Notably, transplant outcomes (engraftment, acute graft-versus-host disease and non-relapse mortality) with cryopreserved products were comparable to those with fresh products. Conclusions: Considering that the emergency situation may persist for months, cryopreserving allogeneic grafts can offer a lifesaving opportunity for patients whose allogeneic transplant cannot be postponed until after the end of the COVID-19 pandemic. [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]

Classification of myeloproliferative neoplasms is based on hematologic, histopathologic, and molecular characteristics, including the BCR-ABL1 and JAK2 V617F or MPL and CALR. Although the different gene mutations ought to be mutually exclusive, several cases with cooccurring BCR-ABL1 and JAK2 V617F or CALR have been identified with a frequency of 0.2-2.5% in the European population. The tyrosine kinase abnormalities appeared to affect independent subclones because imatinib mesylate (IM) treatment induced Ph+-CML remission, whereas the JAK2V617F clone either persisted or clinically expanded after a major response of Ph+-clone. Allogeneic stem cell transplantation is at present the only potentially curative therapy for these patients after therapy with ruxolitinib and TKI inhibitor. We describe the case of 3 young people treated in our institution for the coexistence of BCR/ABL chronic myeloid leukemia and another Philadelphia chromosome-negative (Ph-) Chronic myeloproliferative disease. They received ruxolitinib, imatinib/nilotinib, and allogeneic transplantation with safe and efficient results. [ABSTRACT FROM AUTHOR]

The incidence, risk factors, and prognostic significance of extramedullary involvement (EMI) in adult patients with acute myeloid leukemia (AML) have not been established yet. This study analyzed clinical and biological characteristics, the impact on prognosis, and the cumulative incidence of EMI in a monocentric retrospective series. All adult patients diagnosed with AML observed in our institution between January 2010 and December 2017 were included in the analysis. Overall, 346 AMLs were analyzed. The incidence of EMI was 11% (38 patients). The involved sites were: skin (66%), central nervous system (CNS) (23%), pleura (7%), lymph nodes (5%), peritoneum (2%), spleen (2%), pancreas (2%), breasts (2%) and bones (2%). Most patients (91%) had only one EMI site, while 9% had multiple sites affected at the same time. Twenty-four (63%) patients showed signs of EMI at presentation, while extramedullary relapse occurred in 10 patients (26%); 4 patients had EMI both at presentation and relapse. EMI had a significantly higher frequency in patients with monocytic and myelo-monocytic leukemia subtypes (p<0,0001), CD117-negative (p=0,03) at flow cytometry analysis, MLL rearrangements (p=0.001), trisomy 8 (p=0,02). An analysis regarding treatment, overall survival (OS), and disease-free survival (DFS) was performed only on the 28 patients who experienced EMI at the onset of their disease; one EMI patient receiving best supportive care was excluded from OS analysis. The other 27 patients were treated with: conventional chemotherapy (21 patients), hypomethylating agents (5 patients), and low dose cytarabine (1 patient); 8 patients only (28.5%) received an allogeneic stem cell transplantation (allo-HSCT). After induction therapy, complete remission (CR) rate was 22%, with a median DFS of 7.4 months. The median OS of all 27 EMI patients was 11.6 months (range 2-79); this resulted significantly longer for the 8 EMI patients who undergone allo-HSCT than those (19 patients) who did not receive this procedure (16.7 vs. 8.2 months respectively, p=0.02). Univariate and multivariate analyses showed that undergoing allo-HSCT and achieving CR were the main positive prognostic factors for our population's survival (p<0,0001). This study confirms the poor prognosis for EMI patients. Allo-HSCT, applicable however only in some cases, seems to have a crucial role in these patients' therapeutic approach, being associated with a better prognosis. [ABSTRACT FROM AUTHOR]

Summary: Assessment of minimal residual disease (MRD) is being routinely used to assess response in patients with acute myeloid leukaemia (AML). While it is well established that pre‐transplant positive MRD studies predict for relapse in patients transplanted either from matched sibling donors or matched unrelated donors, it is currently unknown whether MRD has comparable prognostic value in haploidentical stem cell transplantation (haplo‐SCT). To this end we performed a retrospective analysis using the Acute Leukaemia Working Party/European Society of Blood and Marrow Transplantation multicentre registry. All adult AML patients with known MRD status at transplant who underwent a first T‐cell replete haplo‐SCT while in remission between 2006 and 2016 were included. Two hundred and sixty‐five MRD‐negative and 128 MRD‐positive patients were assessed. In multivariate analysis, MRD‐negative patients experienced lower relapse incidence and better leukaemia‐free survival (LFS) compared to MRD‐positive patients. Subset analysis for MRD‐positive patients revealed that patients with donors positive for cytomegalovirus experienced decreased relapse rates as well as increased survival. A 6‐month landmark analysis suggests that the clinical benefit of pre‐transplant MRD negativity in terms of relapse, overall survival and LFS is realized at this time point. Pre‐transplant MRD status is potentially a pivotal prognosticator of outcome in AML patients undergoing T‐cell replete haplo‐SCT. [ABSTRACT FROM AUTHOR]

We report a modified post-transplant cyclophosphamide (PT-CY) regimen, for unmanipulated haploidentical marrow transplants, in 150 patients with acute myeloid leukemia (AML). All patients received a myeloablative regimen, cyclosporine A (CsA) on day 0, mycophenolate on day +1, and PT-CY 50 mg/kg on days +3 and +5. The median age was 51 (range, 17–74) years, 51 (34%) patients had active disease at transplant, and the median follow-up of surviving patients 903 (range, 150-1955) days. The cumulative incidence (CI) of engraftment, acute graft-versus-host disease (GVHD) grade II to IV, and moderate/severe chronic GVHD was 92%, 17%, and 15%, respectively. The 4-year CI of transplant-related mortality (TRM) and relapse was 20% and 24%, respectively. Four-year survival for remission patients was 72% (74% versus 67% for <60 or ≥60 years of age) and 26% for advanced patients (17% versus 41% for <60 or ≥60 years of age). In a multivariate analysis, active disease at transplant was the only negative predictor of survival, TRM and relapse. The original PT-CY regimen can be modified with CsA on day 0, still providing protection against GVHD, low toxicity, and encouraging low relapse incidence in AML patients, also over 60 years of age. [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]

A letter to the editor related to a study on hematological malignancies is presented.

Few data are available to date on the dose of oral valganciclovir as cytomegalovirus (CMV) preemptive therapy in stem cell transplantation patients. This study aimed to evaluate the efficacy and safety of low-dose valganciclovir (900 mg/day) as preemptive treatment in allotransplanted recipients. Valganciclovir was used in 34 patients who underwent allogeneic stem cell transplantation for hematological malignancies at the dose of 900 mg oral administration/day (12 patients, group 1) or 1,800 mg oral administration/day (22 patients, group 2). Thirty-two out of 34 patients (94%) obtained negativization of polymerase chain reaction for CMV at a median of 12.5 days from the beginning of valganciclovir administration (10/12 patients of group 1, 22/22 patients of group 2). We conclude that oral administration of valganciclovir can induce clearance of CMV viral load in about 2 weeks; moreover, lower-dose oral valganciclovir (900 mg/day) has a comparable efficacy to the proposed standard dose (1,800 mg/day). Copyright © 2010 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

Veno-occlusive disease (VOD) of the liver is a severe complication of high-dose chemotherapy and allogeneic or autologous stem cell transplantation with potential fatal outcome. We report a case of severe VOD in a patient with a high-grade B-cell lymphoma. Liver-venule occlusion was confirmed by liver biopsy. Supportive care, fibrinolytic treatment with recombinant tissue plasminogen activator and defibrotide maintenance therapy led to complete resolution of VOD demonstrated at liver biopsy and with a follow-up of 44 months after autologous peripheral blood stem cell transplantation. The literature on VOD has been reviewed. [ABSTRACT FROM AUTHOR]

To evaluate the normalization of lymphocyte subsets several years after autologous peripheral blood stem cell transplantation (aPBSCT) and to detect any differences based on the underlying lymphoproliferative diseases, we analyzed the immunological recovery of 149 patients with Non Hodgkin's Lymphoma (NHL), Hodgkin's Disease (HD), Multiple Myeloma (MM). Lymphocyte recovery was assessed before the transplant, on days 15, 30, 60, 90, 120 and on years 1, 2, 4, 6. Analysis of a total of 709 lymphocytes, including total lymphocyte count, CD3 + , CD4 + , CD8 + , CD4 + /CD8 + ratio, CD19 + , CD3 + HLA-DR + , CD16 + 56 + , was performed. The normalization of total lymphocyte counts was achieved between days 14 to 22 following PBSCT. CD3 + cells count showed a normalization after 2 years in the HD and NHL groups and after 4 years in MM group. CD4 + subset achieved normalization during the sixth year in the 3 groups. The CD8 + and CD19 + lymphocytes subsets achieved normal values in the 3 groups at day 60 and at day 120 respectively. CD16 + 56 + and CD3 + /HLA-DR + lymphocytes showed median values above the normal range starting from day 30. Immunological recovery was similar in all 3 groups. Moreover, the recovery of all subsets evaluated was similarly demonstrated within 6 years after aPBSCT. [ABSTRACT FROM AUTHOR]

• 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]

A letter to the editor is presented in response to a study on the ability of fecal calprotectin as a biomarker of gastrointestinal graft-versus-host disease (GVHD) after transplantation of allogeneic stem cell.

• 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]

• 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]

Background: The standard busulfan-cyclophosphamide myeloablative conditioning regimen is associated with substantial non-relapse mortality in patients older than 40 years with acute myeloid leukaemia who are undergoing allogeneic stem-cell transplantation. Because the combination of busulfan plus fludarabine has been proposed to reduce non-relapse mortality, we aimed to compare this treatment with busulfan plus cyclophosphamide as a preparative regimen in these patients.Methods: We did an open-label, multicentre, randomised, phase 3 trial for patients with acute myeloid leukaemia at 25 hospital transplant centres in Italy and one in Israel. Eligible patients were aged 40-65 years, had an Eastern Cooperative Oncology Group performance status less than 3, and were in complete remission. Patients were randomly assigned 1:1 to receive intravenous busulfan plus cyclophosphamide or busulfan plus fludarabine. Treatment allocations were not masked to investigators or patients. Randomisation was done centrally via a dedicated web-based system using remote data entry, with patients stratified by donor type and complete remission status. Patients allocated to busulfan plus cyclophosphamide received intravenous busulfan 0·8 mg/kg four times per day during 2 h infusions for four consecutive days (16 doses from days -9 through -6; total dose 12·8 mg/kg) and cyclophosphamide at 60 mg/kg per day for two consecutive days (on days -4 and -3; total dose 120 mg/kg). Patients allocated to busulfan plus fludarabine received the same dose of intravenous busulfan (from days -6 through -3) and fludarabine at 40 mg/m(2) per day for four consecutive days (from days -6 through -3; total dose 160 mg/m(2)). The primary endpoint was 1-year non-relapse mortality, which was assessed on an intention-to-treat basis; safety outcomes were assessed in the per-protocol population. This trial has been completed and is registered with ClinicalTrials.gov, number NCT01191957.Findings: Between Jan 3, 2008, and Dec 20, 2012, we enrolled and randomly assigned 252 patients to receive busulfan plus cyclophosphamide (n=125) or busulfan plus fludarabine (n=127). Median follow-up was 27·5 months (IQR 9·8-44·3). 1-year non-relapse mortality was 17·2% (95% CI 11·6-25·4) in the busulfan plus cyclophosphamide group and 7·9% (4·3-14·3) in the busulfan plus fludarabine group (Gray's test p=0·026). The most frequently reported grade 3 or higher adverse events were gastrointestinal events (28 [23%] of 121 patients in the busulfan plus cyclophosphamide group and 26 [21%] of 124 patients in the busulfan plus fludarabine group) and infections (21 [17%] patients in the busulfan plus cyclophosphamide group and 13 [10%] patients in the busulfan plus fludarabine group had at least one such event).Interpretation: In older patients with acute myeloid leukaemia, the myeloablative busulfan plus fludarabine conditioning regimen is associated with lower transplant-related mortality than busulfan plus cyclophosphamide, but retains potent antileukaemic activity. Accordingly, this regimen should be regarded as standard of care during the planning of allogeneic transplants for such patients.Funding: Agenzia Italiana del Farmaco. [ABSTRACT FROM AUTHOR]

Abstract: Epidemiologic investigation of invasive fungal diseases (IFDs) in allogeneic hematopoietic stem cell transplantation (allo-HSCT) may be useful to identify subpopulations who might benefit from targeted treatment strategies. The Gruppo Italiano Trapianto Midollo Osseo (GITMO) prospectively registered data on 1858 consecutive patients undergoing allo-HSCT between 2008 and 2010. Logistic regression analysis was performed to identify risk factors for proven/probable IFD (PP-IFD) during the early (days 0 to 40), late (days 41 to 100), and very late (days 101 to 365) phases after allo-HSCT and to evaluate the impact of PP-IFDs on 1-year overall survival. The cumulative incidence of PP-IFDs was 5.1% at 40 days, 6.7% at 100 days, and 8.8% at 12 months post-transplantation. Multivariate analysis identified the following variables as associated with PP-IFDs: transplant from an unrelated volunteer donor or cord blood, active acute leukemia at the time of transplantation, and an IFD before transplantation in the early phase; transplant from an unrelated volunteer donor or cord blood and grade II-IV acute graft-versus-host disease (GVHD) in the late phase; and grade II-IV acute GVHD and extensive chronic GVHD in the very late phase. The risk for PP-IFD was significantly higher when acute GVHD was followed by chronic GVHD and when acute GVHD occurred in patients undergoing transplantation with grafts from other than matched related donors. The presence of PP-IFD was an independent factor in long-term survival (hazard ratio, 2.90; 95% confidence interval, 2.32 to 3.62; P < .0001). Our findings indicate that tailored prevention strategies may be useful in subpopulations at differing levels of risk for PP-IFDs. [Copyright &y& Elsevier]

Despite advances in graft-versus-host-disease (GVHD) treatment, it is estimated that overall survival (OS) at 2 years for hematopoietic cell transplantation (HCT) recipients who experience steroid-resistant GVHD is 10%. Among recent therapeutic approaches for GVHD treatment, mesenchymal stromal cells (MSCs) hold a key position. We describe a multicenter experience of 11 pediatric patients diagnosed with acute or chronic GVHD (aGVHD, cGVHD) treated for compassionate use with GMP-grade unrelated HLA-disparate donors'' bone marrow-derived MSCs, expanded in platelet-lysate (PL)-containing medium. Eleven patients (aged 4-15 years) received intravenous (i.v.) MSCs for aGVHD or cGVHD, which was resistant to multiple lines of immunosuppression. The median dose was 1.2 × 106/kg (range: 0.7-3.7 × 106/kg). No acute side effects were observed, and no late side effects were reported at a median follow-up of 8 months (range: 4-18 months). Overall response was obtained in 71.4% of patients, with complete response in 23.8% of cases. None of our patients presented GVHD progression upon MSC administration, but 4 patients presented GVHD recurrence 2 to 5 months after infusion. Two patients developed chronic limited GVHD. This study underlines the safety of PL-expanded MSC use in children. MSC efficacy seems to be greater in aGVHD than in cGVHD, even after failure of multiple lines of immunosuppression. [Copyright &y& Elsevier]

: ObjectiveTo evaluate the safety, feasibility, and efficacy of allogeneic stem cell transplantation (SCT) for acute myelogenous leukemia (AML) in a young female coinfected by HIV and HCV undergoing highly active antiretroviral therapy (HAART).: Patient and MethodsA 33-year-old female HIV+, HCV+ in complete remission after standard chemotherapy was submitted to CD34+ selected allogeneic transplantation from her HLA-identical HIV− brother after myeloablative regimen. HAART was started before transplantation, achieving a reduction of HIV load to undetectable levels. GVHD prophylaxis was carried out with cyclosporine A alone.: ResultsThe patient achieved prompt and durable engraftment with acute GVHD grade II easily managed with steroids; CMV prophylaxis was prolonged, no clinically relevant infectious complications developed early after transplantation and during follow-up. HIV viremia was controlled by HAART although medication adherence was reduced early after transplantation and required drug adjustment. There was a gradual recovery of immune cells with normal CD4-cell count 39 months after engraftment, a significantly higher level than before transplantation. At 39 months posttranplantation follow-up the patient is alive and in continuous complete remission with undetectable levels of plasma HIV RNA on HAART.: ConclusionThe introduction of HAART has recently changed the paradigm of AIDS, allowing the control of HIV replication, the reduction of opportunistic infections, and the overall improvement of survival. One may therefore reconsider the current exclusion of patients with AIDS and a concomitant lethal malignancy from programs of high-dose chemotherapy and stem cell transplation, as suggested by this report. [Copyright &y& Elsevier]