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Background Intensified immunochemotherapy with rituximab, doxorubicin, cyclophosphamide, vindesine, bleomycin, and prednisone (R-ACVBP) improves outcomes in younger adults with diffuse large B-cell lymphomas (DLBCL) compared with R-CHOP. Due to vindesine unavailability, we assessed the safety and efficacy of replacing vindesine with vincristine in a modified R-ACVBP protocol (mR-ACVBP). Methods This is a retrospective study including all consecutive adult patients with newly diagnosed DLBCL who received first-line mR-ACVBP. Vindesine was replaced with vincristine 1.5 mg on days 1 and 5 of each cycle. Responders continued with published R-ACVBP consolidation. Patients with inadequate response on interim imaging were offered consolidative autologous stem cell transplantation. Results We identified 56 patients with DLBCL, with a median age of 41 years (range, 21-67). Thirty-seven (66%) patients had an age-adjusted International Prognostic Index of ≥ 2. Complete response was achieved in 41 (80%) patients and partial response in 6 (12%). The most common adverse events during induction were anemia (91%), febrile neutropenia (64%; grade 4 in 46%), thrombocytopenia (39%), and mucositis (21%). Peripheral neuropathy was encountered in 7 (12%) patients (grade 3; n = 1). Two deaths from septic shock were reported in patients with initial poor performance status. After a median follow-up of 17 months, the 2-year progression-free survival and overall survival rates were 86% and 87%, respectively. Conclusion The replacement of vindesine with vincristine in mR-ACVBP seems feasible, with manageable adverse events and excellent 2-year progression-free survival. These data need validation in larger prospective trials.

Bone marrow transplantation is a breakthrough in the world of hematology and oncology. In our region, there is scarce literature studying emergency department visits among BMT patients, as well as their predictors of mortality.This study aimed to assess the frequency, reasons, clinical characteristics and outcomes of patients presenting to the ED after a BMT, and to study the predictors of mortality in those patients. This study also compares those variables among the different types of BMT.This was a retrospective cohort study conducted on all adult patients who have completed a successful BMT and visited the ED.Our study included 115 BMT patients, of whom 17.4% died. Those who died had a higher median number of ED visits than those who did not die. Around 36.5% presented with fever/chills with 29.6% diagnosed with pneumonia on discharge. We found that the odds of mortality were significantly higher among those who presented with dyspnea (p .0005) and AMS (p = .023), among septic patients (p = .001), those who have undergone allogeneic BMT (p = .037), and those who were admitted to the ICU (p = .002). Moreover, the odds of mortality were significantly higher among hypotensive (p ≤0005) and tachycardic patients (p = .015).In our study, we have shown that BMT patients visit the ED very frequently and have high risk of in-hospital mortality. Moreover, our study showed a significant association between mortality and patients with dyspnea, AMS, sepsis, allogeneic BMT type, ICU admission, hypotension and tachycardia.

Background Despite the advantages of bone marrow transplantation (BMT), patients receiving this intervention visit the emergency department (ED) frequently and for various reasons. Many of those ED visits result in hospitalization, and the length of stay varies. Objectives The objective of our study was to identify the patients who were only briefly hospitalized and were thus eligible for safe discharge from the ED. Methods This was a retrospective cohort study conducted on all adult patients who have completed a successful BMT and had an ED visit that resulted in hospitalization. Results Our study included 115 unique BMT with a total number of 357 ED visits. Around half of those visits resulted in a short hospitalization. We found higher odds of a short hospitalization among those who have undergone autologous BMT (95%CI [1.14–2.65]). Analysis of the discharge diagnoses showed that patients with gastroenteritis were more likely to have a shorter hospitalization in comparison to those diagnosed with others (95%CI [1.10–3.81]). Furthermore, we showed that patients who presented after a month from their procedure were more likely to have a short hospitalization (95%CI [1.04–4.87]). Another significant predictor of a short of hospitalization was the absence of Graft versus Host Disease (GvHD) (95%CI [2.53–12.28]). Additionally, patients with normal and high systolic blood pressure (95%CI [2.22–6.73] and 95%CI [2.81–13.05]; respectively), normal respiratory rate (95%CI [2.79–10.17]) and temperature (95%CI [2.91–7.44]) were more likely to have a shorter hospitalization, compared to those presenting with abnormal vitals. Likewise, we proved higher odds of a short hospitalization in patients with a quick Sepsis Related Organ Failure Assessment score of 1–2 (95%CI [1.29–5.20]). Moreover, we demonstrated higher odds of a short hospitalization in patients with a normal platelet count (95%CI [1.39–3.36]) and creatinine level (95%CI [1.30–6.18]). Conclusion In our study, we have shown that BMT patients visit the ED frequently and many of those visits result in a short hospitalization. Our study showed that patients presenting with fever/chills are less likely to have a short hospitalization. We also showed a significant association between a short hospitalization and BMT patients without GvHD, with normal RR, normal T °C and a normal platelet count.

Background Graft-versus-host disease (GVHD) is a major cause of mortality after allogeneic stem-cell transplantation. Posttransplantation cyclophosphamide (PT/CY) has become standard prophylaxis of GVHD in T-replete haploidentical transplantation. The question is whether adding antithymocyte globulin (ATG) to PT/CY may further reduce the incidence of GVHD compared to PT/CY only. Patients and Methods We retrospectively studied 268 patients undergoing myeloablative haploidentical transplantation with thiotepa, busulfan, and fludarabine (TBF) conditioning. Sixty-nine patients (26%) received ATG. Results In the ATG group, 3% died due to GVHD versus 8% in the no ATG group. The 100-day and 1-year nonrelapse mortality (NRM) was 0% and 19%, respectively, in the whole cohort. On univariate analysis, the 1-year NRM was 8% versus 23% in patients receiving ATG and no ATG, respectively (P = .005). The no ATG group had a higher incidence of acute GVHD at 12 months compared to the ATG group (22% vs. 12%, respectively, P = .029). The ATG group had better overall survival at 12 months compared to the no ATG group (79% vs. 69%, P = .029). On multivariate analysis, adding ATG to PT/CY had no significant impact on any of the outcomes. A low disease risk index was associated with better overall survival and lower NRM, while Hematopoietic Cell Transplantation-Specific Comorbidity Index (HCT-CI) score ≥ 3 was associated with higher NRM. Conclusion ATG can be safely used as part of the pretransplantation conditioning and does not increase the incidence of relapse or complications after transplantation.

To evaluate polymorphisms in genes of drug metabolizing enzymes and transporters involved in cyclosporine and/or voriconazole disposition among patients undergoing allogeneic hematopoietic cell transplantation (allo-HCT).DNA from forty patients was genotyped using the DMETPlus array. The average ratio of cyclosporine concentration/dose (C/D in (ng/mL)/(mg/kg)) per participant's weight was computed using available trough levels and daily doses.The C/D cyclosporine ratio was significantly higher when it was administered with voriconazole as compared to when it was administered alone: median: 116.75 vs. 25.40 (ng/mL)/(mg/kg) with and without voriconazole respectively, (P 0.001). There was also a significant association between the C/D cyclosporine ratio combined with voriconazole and the ABCB1 2677 G T A (rs2032582) genetic polymorphism (P = 0.05). In parallel, ABCB1 variant allele carriers had higher creatinine in combination therapy with a median creatinine (mg/dL) of 0.74 vs. 0.56 for variant allele carriers vs. reference; P = 0.003. Interestingly, CYP2C9, CYP2C19, and CYP3A5 extensive metabolizers tended to be associated with lower cyclosporine C/D ratio when combined with voriconazole, but the results were not statistically significant.To the best of our knowledge, this is the first pharmacogenetic study on the interaction between voriconazole and cyclosporine in patients undergoing allo-HCT. Results suggest that the ABCB1 2677 G T A genetic polymorphism plays a role in this interaction with cyclosporine related nephrotoxicity. Pre-emptive genotyping for this genetic variant may be warranted for cyclosporine dose optimization. Larger studies are needed to potentially show significant associations with more candidate genes such as CYP3A4/5, CYP2C9, and CYP2C19, among others.

Given the absence of consensus on oral feeding of patients undergoing allogeneic hematopoietic transplantation, the ninth workshops of practice harmonization of the Francophone Society of Bone Marrow Transplantation and Cellular Therapy (SFGM-TC) allocated one session to address this topic, especially during the hospitalization. A questionnaire was sent to all SFGM-TC pediatric and adult centers in order to investigate oral feeding practices. The results demonstrated a large disparity among centers regarding oral feeding. Here, we report our recommendations regarding the oral feeding after allogeneic hematopoietic cell transplantation in terms of quality, quantity and bacterial authorized load.

This prospective, observational, multicenter study evaluated the real-world incidence of invasive fungal infection (IFI) during and after micafungin prophylaxis in France. Patients with a hematological malignancy/solid tumor received micafungin prophylaxis according to usual clinical practice and were followed for 3 months. Primary endpoint was breakthrough IFI incidence during prophylaxis. Secondary endpoints included the identification of IFI risk factors, IFI incidence during follow-up, and adverse events (AEs). One hundred and fifty patients (55 children, 95 adults) were enrolled. Micafungin prophylaxis was initiated at 50 mg in adults and at a median 1.01 mg/kg (range: 0.6–2.2) in children. Fifteen patients (10%) experienced an IFI during prophylaxis. IFI breakthrough occurred in 15% children, 7% adults, 3.1% allogeneic transplant patients, 8.7% acute myeloid leukemia (AML)/myelodysplastic syndrome (MDS) patients, 7.0% other patients (never allotransplanted/non-AML/MDS). Nineteen patients (12.7%) experienced an IFI during 3-month follow-up. Micafungin was well tolerated with few treatment-related AEs, supporting its use in this patient population in France.

Severe aplastic anemia (SAA) is a hematological disease resulting in pancytopenia due to bone marrow failure. Treatment consists of immunosppressive therapy, or allo-SCT. Patients with aplastic anemia are predisposed to invasive fungal infections due to mucormycosis. Till now, syngeneic SCT in the context of active mucormycosis infection for patients with severe aplastic anemia is lacking in the literature.Here, we report a case of severe aplastic anemia with disseminated mucormycosis infection undergoing syngeneic transplant. Keywords: Mucormycosis, Severe aplastic anemia, Syngeneic transplantation

Background Gastrointestinal (GI) graft versus host disease (GVHD) occurs in up to 40% of patients undergoing allogenic hematopoietic stem cell transplantation (HSCT). However, the optimal endoscopic approach is still unclear and the area of the GI tract with the highest diagnostic yield is still a topic of debate. Objective We compared the diagnostic yield of different anatomic site biopsies in the diagnosis of GI GVHD and assessed the correlation of endoscopic findings with histopathology. Methods All cases of biopsy proven GI GVHD were obtained from pathology database AUBMC between 1/1/2005 and 31/8/2017. We retrospectively analyzed the demographical, clinical and endoscopic data. Results Nineteen patients were diagnosed with GI GVHD over 17.6 years. The most common presenting symptom was severe diarrhea (18 patients, 94.7%). Combining upper endoscopy and sigmoidoscopy with biopsies had the highest diagnostic yield of 90% in diagnosing GI GVHD compared to 63.6%, 78.6% and 77.8% for upper endoscopy, sigmoidoscopy and colonoscopy respectively. In macroscopically normal mucosa, the recto-sigmoid and duodenal biopsies had the highest diagnostic yield (75%). As for the macroscopically abnormal mucosa, the highest yield was for the recto-sigmoid biopsies (100%) in lower endoscopy and duodenal biopsies in the upper endoscopy (60%). Conclusion In a patient suspected to have GI GVHD, the best endoscopic approach is the combination of upper endoscopy and flexible sigmoidoscopy with biopsies of normal as well as abnormal mucosa. It should be emphasized that normal mucosa be biopsied especially in the duodenum and recto-sigmoid for a better diagnostic yield.

JACIE (Joint Accreditation Committee ISTC EBMT) regulations and standards impose a quality and safety requirement for graft reinjection by nurses. However, the standards do not provide a step-by-step graft reinjection procedure. Because of high medical team turnover, the opening of new transplant centers, and continual questions from colleagues trying to decipher the JACIE standards, the need for a specific procedure goes without saying. We collected graft reinjection procedures from each SFGM-TC center that participated in our survey, thus creating an inventory of the different steps that make up graft reinjection. In addition to reviewing the main regulatory texts and JACIE standards, we sought advice from medical and cellular therapy experts. We observed that most centers use a mix of practices and some unjustified practices. In some transplant units, it is still standard practice to defrost cell therapy products in the transplant unit. Caregivers are aware of the need for a rigorous application of the regulatory requirements and are willing to administer a procedure that provides specific steps for each stage of the process. In this workshop, we questioned each stage of the graft reinjection procedure, which helped us define clear methods of implementation. In the form of a checklist, we offer bone marrow and stem cell transplant units a step-by-step procedure.

Context Autologous hematopoietic stem cell transplant (ASCT) has become the mainstay treatment for many hematological malignancies and solid tumors. An adequate number of stem cells must be collected for better ASCT outcomes, which is challenging in 5%–30% of patients. To improve mobilization, plerixafor is used, along with granulocyte colony-stimulating factor. Objective To evaluate the real-life efficacy of plerixafor and to identify factors associated with poor mobilization. Design and Setting This is a retrospective, single-center study involving patients who received plerixafor pre-ASCT between January 2013 and December 2020 at a tertiary care center in Lebanon. Patients We identified a total of 72 consecutive adult patients. Patients who received plerixafor were divided into two groups: poor mobilizers with pre-emptive use before first apheresis for those with peripheral CD34+ stem cells (PSC) 20 cells/µL. Main Outcome Measures The main endpoints were to evaluate characteristics of poor mobilizers, stem cell yields pre- and post-plerixafor, as well as the time to neutrophil and platelet engraftment. Results The median age at diagnosis was 54 years (12–73). 60% were males. 50 (70%) patients had multiple myeloma (MM), 12 (15%) had non-Hodgkin lymphoma, 7 (10%) had Hodgkin lymphoma, and 3 (4%) had solid tumors and Waldenstrom macroglobulinemia. The median follow-up was 9 months (1–59). 59 (82%) patients had low PSCs, requiring pre-emptive plerixafor prior to apheresis. 62% of MM and 54.5% of non-MM patients needed >1 collection. 97% of all patients collected CD34+ >2×106cells/kg post-plerixafor. The median collected final CD34+ cells post-plerixafor was 4.4×106/kg (1.84–18.62). Factors associated with poor mobilization were male gender, age at diagnosis >55 years, MM, and bone marrow involvement (p=0.041, p=0.031, p=0.04, and p=0.012, respectively). Median times to absolute neutrophil count (ANC) and platelet engraftment were 11 (4–26) and 17 (4–28) days, respectively. A longer ANC engraftment (>2 weeks) was observed in patients who were infused Conclusion These results can guide us to use plerixafor early in selected patients who are predicted to fail mobilization.

Context: The frontline treatment of chronic phase (CP) chronic myeloid leukemia (CML) with nilotinib has resulted in a higher rate of major molecular response (MMR) and complete cytogenetic response (CCyR) at 12 months compared to imatinib but at a higher cumulative cost and increased risk of serious adverse events. A treatment strategy aimed at maintaining long-term efficacy while minimizing both toxicities and costs is needed. Objective: The aim of the study is to evaluate the efficacy and safety of a response-directed switch from nilotinib to imatinib in patients newly diagnosed with CP-CML. Design: This is a single-center, prospective, pilot phase 2 open-label study including adult patients newly diagnosed with CP-CML screened and treated at the American University of Beirut Medical Center in Lebanon. Interventions: Patients were treated with nilotinib 300 mg orally twice daily for 12 months, and those who achieved CCyR were shifted to imatinib 400 mg orally daily, with regular follow-ups at 3, 6, 12 months, and then every 6 months thereafter. Main Outcome Measures: The primary endpoint was to evaluate the efficacy of imatinib in maintaining cytogenetic and molecular responses achieved at 12 months after nilotinib treatment in at least 85% of patients. Results: Thirteen patients were enrolled in the study. Eleven patients completed one year of nilotinib and switched to imatinib 400 mg daily as per protocol. At 3 months, all patients achieved complete hematologic response, with 7 (54%) patients having early molecular response. At 12 months, all patients achieved CCyR, of whom 5 (45%) and 4 (36%) patients achieved MMR and MR4.5, respectively. Three (27%) patients switched back to nilotinib after 18, 24, and 51 months, respectively: one patient lost CCyR after 18 months, and two patients were imatinib-intolerant. After a median follow-up of 60 months, all patients (n=12) were alive and in MMR, 6 (50%) of them in continuous MR4.5. No new safety concerns emerged in the study. Conclusions: These findings suggest that a response-directed switch from nilotinib to imatinib at 12 months is capable of maintaining long-term CCyR, with manageable side effects. This approach warrants further exploration with larger prospective trials.

Introduction The optimal intensity of myeloablation with a reduced-toxicity conditioning regimen to decrease relapse rate after allogeneic stem-cell transplantation without increasing transplant-related mortality (TRM) has not been well established. Materials and Methods We compared outcomes between 5 mg/kg (T5) and 10 mg/kg (T10) thiotepa-based conditioning regimens in 29 adults who underwent allogeneic stem-cell transplantation for hematologic malignancies. Results After a median follow-up of 11 months, TRM was 0% and 14% at 100 days and 1 year, respectively, with TRM observed only in the T5 group ( P = .016). The relapse incidence at 1 year was 20%. No patient had disease in first complete remission at the time of transplantation. At 1 year, progression-free and overall survival were 30% versus 87% ( P = .012) and 46% versus 87% ( P = .008) in the T5 and T10 groups, respectively. In univariate and multivariate analysis, only age at transplantation and total dose of thiotepa had a significant impact on TRM, overall, and progression-free survival. Conclusion Patients deemed fit to receive T10-based conditioning for allogeneic stem-cell transplantation to treat high-risk hematologic malignancies had better overall and progression-free survival than those who received T5 with no additional toxicities. Patients should be stratified before conditioning, and those judged fit should receive T10, while the others should consider alternative reduced-intensity conditioning regimens.

Context: Relapsed/refractory (R/R) acute myeloid leukemia (AML) patients have very poor prognosis. Myeloablative conditioning followed by allogeneic hematopoietic cell transplantation (allo-HCT) remains the only option to achieve disease control in such high-risk patients. Objective: The aim of this study is to evaluate the efficacy and safety of myeloablative conditioning followed by allo-HCT in patients with R/R AML in active disease. Design: This is a single center, observational, retrospective study of patients diagnosed with R/R AML (2016-2020) and treated at the American University of Beirut Medical Center in Lebanon. Main Outcome Measures: Data regarding patient baseline characteristics, disease-related factors, transplant outcomes, and complications were collected. Results: We identified 16 patients with R/R AML who underwent allo-HCT in active disease, with median three lines of treatments. The median age at transplant was 49 years (range 33-75). Of them, 8 (50%) were males, 9 (56%) had high-risk ELN, 12 (75%) had haploidentical donors and 4 (25%) had full matched related donors. Thirteen (81%) patients received sequential conditioning, two (13%) received clofarabine with total body irradiation, and one (6%) received fludarabine and busulfan. Fourteen (87%) patients received anti-thymocyte globulin. Neutrophil and platelet engraftment were seen in 14 (88%) and 9 (56%) patients, respectively. At day 30 post-allo-HCT, 11 (68%) patients had complete remission (CR). At day 100, 10 (63%) patients were alive, 7 out of them (44%) were disease free with full donor chimerism. After a median follow-up of 5.3 months (range 0.2 – 27.5) post-allo-HCT, the median overall survival was 2.9 months (range 0.3-27.5), with active leukemia being the primary cause of death (62%), only four patients (25%) died from transplant related complications. Univariate analysis of factors affecting OS showed improved survival in patients receiving post-allo HCT 5-azacitidine and donor lymphocyte infusion (p= 0.035 and p= 0.0341, respectively). Three patients (19%) developed acute GVHD and one of them died due to its complications. CMV and EBV reactivations were seen in 38% and 6% of cases. Conclusion: Myeloablative conditioning followed by allo-HCT for patients with R/R AML in active disease can confer a disease control in a subset of patients, with acceptable rate of transplant-related mortality.

Context: Numerous factors may affect the survival outcomes of patients with acute myeloid leukemia (AML), mainly disease-related and treatment-related factors. The impacts of other factors, such as the insurance status and the distance to healthcare facilities, are still unclear and may differ between different healthcare systems. Objective: The aim of this study is to investigate the effects of insurance status and distance to the treatment center on the survival of AML patients. Design: This is a single-center, observational, retrospective study of patients diagnosed with AML (2015–2020) and treated at the American University of Beirut Medical Center in Lebanon. Main Outcome Measures: Data regarding patient baseline characteristics, disease-related factors, insurance status, and area of residence were collected. Multivariate Cox regression analysis was used to identify main independent predictors of overall survival (OS). Results: We identified 142 AML patients with a median age of 52 years (range 18–86). Of them, 91 (64%) were males, 75 (53%) had ELN intermediate risk, and 88 (62%) patients received intensive chemotherapy. After a median follow-up of 22.4 months, the 2-year RFS and OS were 65% and 71%, respectively. The median RFS and OS were 63 months and not reached, respectively. A Cox regression model for OS was done using the following variables: age, gender, body mass index, ACE-27 comorbidity score, smoking status, insurance status, distance from the center, ELN classification, treatment used, and allotransplant. A higher risk of death was seen among the uninsured patients and those living beyond 40 km from the treatment center compared with fully insured patients and those living in proximity to the center (hazard ratio [HR]: 3.65; 95% CI [1.79, 7.45], p-value Conclusions: The outcome of patients with AML does not depend only on disease-related factors, as the insurance status and the distance from the area of residence to the treatment center were found to be independent predictors of survival in AML patients.

John Cunningham virus (JCV) reactivation, occurring mainly in immunocompromised patients, leads to progressive multifocal leukoencephalopathy, an uncommon but lethal disease. JCV reactivation after T-cell replete haploidentical stem cell transplantation, in the pre-cyclophosphamide era, is poorly represented in the literature. We therefore describe two cases of acute myeloid leukemia who developed JCV reactivation after receiving cyclophosphamide and rituximab post haploidentical stem cell transplantation, and review the literature, aiming to a better understanding of the disease course and its risk factors.

Despite advances in the treatment of acute myeloid leukemia (AML), cytotoxic chemotherapy remains the standard induction regimen.In this single center retrospective study, we assessed outcomes of 99 consecutive adult AML patients treated with a risk-adapted strategy with a median follow-up of 35.5 months.We identified 24 (24 %), 55 (56 %) and 20 (20 %) patients classified as favorable-, intermediate-, and adverse- risk group respectively, according to the European LeukemiaNet (ELN) 2017 classification. Patients either received idarubicin and cytarabine induction chemotherapy with or without FLT3 inhibitors or hypomethylating agents based on age and comorbidity. The complete response (CR) rate was 76 % (82 % and 61 % in patients aged60 and ≥ 60, respectively). For the whole cohort, the 3-year overall survival (OS) was 53 %, being 62 % and 30 % in patients aged60 and ≥ 60, respectively. The 3-year leukemia-free survival (LFS) was 54 %, with 56 % and 45 % in patients aged60 and ≥ 60, respectively. The 3-year LFS were 58 %, 62 % and 25 % for patients within ELN favorable-, intermediate-, and adverse-risk groups respectively. Twenty-seven (36 %) out of 75 patients with intermediate- and adverse-risk disease underwent allogeneic hematopoietic cell transplantation (allo-HCT) in first CR with 92 % of them receiving post-transplant maintenance consisting of azacitidine in 19 (76 %) patients or sorafenib in 6 (24 %) patients. Of these patients younger than 60 years, the 3-year OS and LFS were 85 % and 69 %, respectively.These results indicate an improved OS for AML patients especially in intermediate-risk category who were treated with a total therapy consisting of induction chemotherapy followed by allo-HCT and post-transplant maintenance.

To find out prognostic factors and to investigate different therapeutic approaches, we report on 147 consecutive patients who relapsed after allogeneic hematopoietic stem cell transplantation (allo-HSCT) for myelodysplastic syndrome (MDS). Sixty-two patients underwent immunotherapy (IT group, second allo-HSCT or donor lymphocyte infusion), 39 received cytoreductive treatment alone (CRT group) and 46 were managed with palliative/supportive cares (PSC group). Two-year rates of overall survival (OS) were 32%, 6%, and 2% in the IT, CRT, and PSC groups, respectively (P.001). In multivariate analysis, 4 factors adversely influenced 2-year rates of OS: history of acute graft-versus-host disease (hazard ratio [HR], 1.83; 95% confidence interval [CI], 1.26 to 2.67; P = .002), relapse within 6 months (HR, 2.69; 95% CI, .82 to 3.98; P.001), progression to acute myeloid leukemia (HR, 2.59; 95% CI, 1.75 to 3.83; P.001), and platelet count50 G/L at relapse (HR, 1.68; 95% CI, 1.15 to 2.44; P = .007). A prognostic score based on those factors discriminated 2 risk groups with median OSs of 13.2 versus 2.4 months, respectively (P.001). When propensity score, prognostic score, and treatment strategy were included in Cox model, immunotherapy was found to be an independent factor that favorably impacts OS (HR, .40; 95% CI, .26 to .63; P.001). In conclusion, immunotherapy should be considered when possible for MDS patients relapsing after allo-HSCT.

Context Outcomes of haplo-identical hematopoietic stem cell transplantation (haploSCT) have recently improved due to better control of allo-reactive reactions related to the major HLA mismatch between the recipient and the donor. Presence of pretransplant donor-specific anti-HLA antibodies (DSA) is associated with higher risk of graft failure. However, little is known regarding the association between the presence of these antibodies and platelet transfusion refractoriness (PTR) post-haploSCT that could predict poor transplant outcomes. Objective The aim of this study is to evaluate the association between DSA status of the recipient and the corrected platelet count increment (CCI) from day 0-100 post-haploSCT as an objective measure of PTR. Design This is a retrospective study that comprises chart review of patients who underwent haplo-SCT between June 2015 and January 2020 at the American University of Beirut medical center in Lebanon. Main outcome measures Pretransplant panel reactive antibodies (PRA) and DSA status at the time of transplant were collected, and the 24-hour CCI was calculated for every platelet donor transfusion. Results We identified 69 patients with a median age of 36 years (range: 16-77). 44 patients (64%) were males and 52 patients (75%) had myelodysplastic syndrome or acute leukemia. Median time from diagnosis to transplant was 13.8 months (range: 2.5-91.7), and 43 patients (62%) were in complete remission at transplant. Of all patients, only 6 patients (8.7%) were DSA+ at time of transplant, 14 (20.3%) were PRA+/DSA-, and the remaining 49 (71%) were PRA-. All 6 patients with DSAs underwent desensitization with a median MFI decrease of 375 (range: -541-1603). One of these 6 did not reach platelet nor leukocyte engraftment. Patients with persistent DSAs had lower mean CCI (9.27, range: 4.58-12.37) compared to those without DSAs (mean CCI: 11.93, range: 1.34-29.71; p=0.017). Statistical significance was maintained upon comparing PRA+DSA+ patients to PRA+DSA- and to PRA- patients with mean CCI of 14.04 (range: 1.39-29.71; p=0.005) and 11.38 (range: 1.34-28.00, p=0.024), respectively. Conclusions Presence of anti-HLA DSAs in haploSCT recipients, even at MFI lower than 1500, was associated with increased PTR. Larger number of patients is needed to evaluate its impact on survival outcomes.

We investigated the impact of rabbit antithymocyte globulins (ATG) on patient outcomes after allogeneic stem cell transplantation (allo-SCT) for progressive myelodysplastic syndrome (MDS). Of the 242 consecutive patients who underwent allo-SCT for progressive MDS between October 1999 and December 2009, 93 received ATG (ATG group) at the median dose of 5 mg/kg, whereas 149 patients did not (no-ATG group). Donors were sibling (n = 153) or HLA-matched unrelated (n = 89). Patients received blood (n = 90) or marrow (n = 152) grafts after either myeloablative (n = 109) or reduced-intensity (n = 133) conditioning. Three-year overall and event-free survival, nonrelapse mortality, relapse, and chronic graft-versus-host disease (GVHD) development were not significantly different between the 2 groups. In contrast, acute grade II to IV GVHD occurred more often in the no-ATG group (55% of the patients) than in the ATG group (27%, P

Nonmyeloablative (NMA) regimens allow the use of allogeneic hematopoietic stem cell transplantation (allo-HSCT) in patients considered unfit for standard myeloablative conditioning (MAC) regimens using high-dose alkylating agents with or without total body irradiation (TBI). Reduced-intensity conditioning (RIC) regimens, based on fludarabine (Flu), busulfan (Bu), and rabbit antithymocyte globulin (r-ATG), represent an intermediate alternative between NMA and MAC regimens. This platform was subsequently optimized by the introduction of i.v. Bu and the use of 5 mg/kg r-ATG, based on the hypothesis that these modifications would improve the safety of RIC allo-HSCT. Here we report a study conducted at our institution on 206 patients, median age 59 years, who underwent allo-HSCT after conditioning with Flu, 2 days of i.v. Bu, and 5 mg/kg r-ATG (FBx-ATG) between 2005 and 2012. The prevalence of grade III-IV acute graft-versus-host disease (GVHD) was 9%, and that of extensive chronic GVHD was 22%. Four-year nonrelapse mortality (NRM), relapse, and overall survival (OS) rates were 22%, 36%, and 54%, respectively. NRM tended to be influenced by comorbidities (hematopoietic cell transplantation–specific comorbidity index [HCT-CI]

We retrospectively analyzed outcomes of a CD34(+)-selected stem cell boost (SCB) without prior conditioning in 32 patients (male/22; median age of 54 years; range, 20 to 69) with poor graft function, defined as neutrophils ≤1.5 x 10(9)/L, and/or platelets ≤30 x 10(9)/L, and/or hemoglobin ≤8.5 g/dL). The median interval between stem cell transplantation and SCB was 5 months (range, 2 to 228). The median number of CD34(+) and CD3(+) cells were 3.4 x 10(6)/kg (.96 to 8.30) and 9 x 10(3)/kg body weight (range, 2 to 70), respectively. Hematological improvement was observed in 81% of patients and noted after a median of 30 days (range, 14 to 120) after SCB. The recipients of related grafts responded faster than recipients of unrelated grafts (20 versus 30 days, P = .04). The cumulative incidence of acute (grade II to IV) and chronic graft-versus-host disease (GVHD) after SCB was 17% and 26%, respectively. Patients with acute GVHD received a higher median CD3(+) cell dose. The 2-year probability of overall survival was 45%. We suggest that SCB represents an effective approach to improve poor graft function post transplantation, but optimal timing of SCB administration, anti-infective, and GVHD prophylaxis needs further evaluation.

We prospectively evaluated in high-risk myeloma patients the efficacy and toxicity of tandem autologous hematopoietic stem cell transplantation (auto-HSCT) followed by reduced-intensity conditioning (RIC) and allogeneic (allo)-HSCT with bortezomib and donor lymphocyte infusions introduction after allo-HSCT (group 1). Results were compared with results from tandem auto-RIC-allo-HSCT without bortezomib (group 2). Groups 1 and 2 were compared to matched patients not receiving allo-HSCT from the Intergroupe Francophone du Myelome prospective studies. Allo-HSCT groups included 25 patients (12 in group 1, 13 in group 2). All patients engrafted. There were 8 acute GVHD (7 grade II [3 in group 1], 1 grade III in group 1)] and 11 chronic GVHD (3 limited [in group 1], 8 extensive [1 in group 1]). Matched population included 36 controls for group 1 and 39 for group 2. After a median follow-up of 55 months (range, 3–142 months), median overall survival was not reached in group 1 versus 65 months (51-not reached [NR]) in its matched group ( p = 0.027); it was 96 months (49-NR) in group 2 versus 91 months (32-NR) in its matched group ( p = 0.77). Median progression-free survival was 49 months (29-NR) in group 1 and was 25 months (range, 21–35 months) in its matched group ( p = 0.0045); it was 31 months (22-NR) in group 2 and 28 months (range, 21–40 months) in its matched group ( p = 0.0776). Tandem auto-RIC–allo-HSCT including new molecules and immunomodulation after transplantation could be used as a first-line treatment for high-risk myeloma patients.

To evaluate the efficacy and toxicity of reduced-intensity conditioning (RIC) combining fludarabine, low-dose total body irradiation (TBI) and rituximab before allogeneic hematopoietic stem cell transplantation (allo-HSCT) from human leucocyte antigen (HLA) identical siblings, we conducted a prospective study in patients ≤65 years old with advanced chronic lymphocytic leukemia (CLL) stage B or C in response after a salvage treatment. Conditioning included rituximab (375 mg/m² on day 5), fludarabine (30 mg/m² from day 4 to day 2), TBI (2 Gy on day 0), and rituximab (500 mg/m² on days 1 and 8). Forty patients were included, 34 (85%) were male with a median age of 54 years (range, 35–65 years), 38 (95%) were in B stage, and 2 were in stage C; only 7 patients (17%) were in complete response. Seven (17%) patients did not receive rituximab. Thirty-nine (98%) patients engrafted, 17 patients developed acute graft-versus-host disease (GVHD) grade ≥II with a cumulative incidence at 3 months of 44% (36–52) with a significant protective effect of rituximab ( p = 0.02). The cumulative incidence of chronic GVHD was 29% (21–36) at 12 months for both limited and extensive forms. The median overall survival was not reached with 5-years probability of 55% (41–74). The multivariate analysis showed a positive effect of rituximab on overall survival and event-free survival (hazard ratio [HR] = 0.1 [0–0.6], p = 0.02; and HR = 0.1 [0–0.4], p = 0.035, respectively). The association of fludarabine, TBI, and rituximab is feasible, well tolerated, and allows better outcomes in advanced CLL.

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