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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.

Relapse rates following allogeneic stem cell transplantation for acute myeloid leukemia remain unacceptably high and a major cause of death. Maintenance therapies post-transplant administered either to patients with impending relapse or at high risk of relapse could present a strategy to improve survival and overall outcomes. With the increasing use of molecular and genomic characterization of the disease, more novel therapies became available as maintenance strategies. These options were, however, hindered by excessive toxicities, mostly hematologic, especially with the use of myeloablative conditioning regimens. Several key questions have also emerged including the efficacy of these therapies, the duration of maintenance, as well as the potential modulation of the graft and the immune microenvironment. These issues are further complicated by the paucity of well-designed prospective randomized clinical trials evaluating these agents. Future directions in this field should include better risk stratification and patient selection based on assays of minimal residual disease, as well as the incorporation of novel targets and pathways of leukemogenesis. In this article, we highlight the current evidence behind the use of post-transplant maintenance therapy, the optimal patient and disease selection, as well as the challenges faced by these strategies in an area that remains quite controversial. We will focus on therapies targeting leukemia stem cells that directly or indirectly modulate the allografted immune microenvironment and augment the graft-versus-leukemia impact.

Micronutrient intake among hematopoietic stem cell transplant (HSCT) recipients is poorly studied. This randomized control trial (RCT) assessed the effect of nutritional counseling on micronutrient intake post HSCT. Patients with hematological malignancies receiving HSCT were randomized at hospital discharge into an intervention group (IG) and a control group (CG) between 2016 and 2017. IG received individualized nutritional counseling in the first 3 months post HSCT while CG received general qualitative education without reinforcement. At assessment points (hospital admission, discharge, 30, 60, and 100 days post HSCT termed T4), 24-h recalls were analyzed, and micronutrient intake was compared to patients' individual needs. Results were reported as percentages of dietary reference intake. Groups (IG, n = 22 and CG, n = 24) had similar characteristics pre HSCT. Copper and α-tocopherol intake at T4 were significantly better in IG. Many B vitamins, vitamin C, Manganese, Potassium, Zinc, and vitamin K improved in IG only at T4 compared to baseline intake. Median vitamin D intake remained low in both groups with

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.

Background: Invasive fungal infections (IFI) following allogeneic stem cell transplant (allo-HCT) are associated with high morbidity and mortality. Primary prophylaxis using voriconazole has been shown to decrease the incidence of IFI. Methods: We conducted a retrospective analysis at the Bone Marrow Transplant (BMT) unit of the American University of Beirut including 195 patients who underwent allo-HCT for hematological malignancies and received voriconazole as primary prophylaxis for IFI. The primary endpoints were based on the incidence of IFI at day 100 and day 180, and the secondary endpoint based on fungal-free survival. Results: For the study, 195 patients who underwent allo-HCT between January 2015 and March 2021 were included. The median age at transplant was 43 years. Of the patients, 63% were male, and the majority of patients were diagnosed with acute myeloid leukemia (AML) (60%). Voriconazole was given for a median of 90 days and was interrupted in 20 patients. The majority of IFI cases were probable invasive aspergillosis (8%). The incidence of IFI including proven, probable and possible IFI was 34%. The incidence of proven and probable IFI was 5% were 8%, respectively. The incidence of proven-probable (PP-IFI) was 5.1% at day 100 and 6.6% at day 180. The majority of PP-IFI cases were invasive aspergillosis (8%). A univariate analysis of patients, transplant characteristics and IFI showed a significant correlation between the type of donor, disease status before transplant, graft-versus-host disease prophylaxis used and incidence of IFI. Only disease status post-transplant showed a significant correlation with fungal-free survival in the multivariate analysis. Conclusion: Primary prophylaxis with voriconazole in allo-HCT is associated with a low incidence of IFI. More studies are required to compare various antifungal agents in this setting.

Vaccines against COVID-19 have demonstrated a remarkable efficacy in decreasing hospitalisations and deaths; however, clinical trials leading to vaccine approvals did not include immunocompromised individuals such as patients receiving antineoplastic therapies. Emerging data suggest that patients on active anti-cancer therapy may have a reduced immune response to COVID-19 vaccination compared to the general population and may be at greater risk of COVID-19 infection as measures to reduce transmission in the community are relaxed. We report preliminary data from the American University of Beirut Medical Center in Lebanon demonstrating relatively low seroconversion rates. Of 36 patients on active anti-cancer therapy who had received two doses of vaccine, 17% were negative for Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) anti-spike IgG. These results highlight the importance of maintaining strict precautionary measures against COVID-19 in patients on immunosuppressive treatment. There is an urgent need for active monitoring of immune response post-vaccination in prospective studies involving populations from diverse resource settings.

The World Health Organization-designated Eastern Mediterranean region (EMRO) consists of 22 countries in North Africa and Western Asia with a collective population of over 679 million. The area comprises some of the wealthiest countries per capita income and some of the poorest. The population structure is also unique and contrasts with western countries, with a much younger population. The region sits in the heart of the thalassemia belt. Many countries have a significant prevalence of sickle cell disease, and cancer is on the rise in the region. Therefore, the strategic priorities for the growth and development of hematopoietic stem cell transplantation (HSCT) differ from country to country based on resources, healthcare challenges, and prevalent infrastructure. Thirty-one reporting teams to the Eastern Mediterranean Blood and Marrow Transplantation Group have active HSCT programs in 12 countries; allogeneic transplants outnumber autologous transplants, and the proportion of allotransplants for non-malignant conditions is higher in the EMRO region than in Western Europe and North America. The vast majority (99%) of allotransplants are from matched related donors. Matched unrelated donors and other alternate donor transplants are underutilized. The chance of finding a matched related donor for allografts is higher, with a significant chance of finding matched donors among non-sibling related donors. Reasons for relatively lower rates of transplants compared with other countries are multifactorial. Capacity building, development of newer centers, innovative funding, and better utilization of information technology are required to make transplantation as an accessible modality to more patients. Cost-effectiveness and cost-containment, regulation, and ensuring quality will all be priorities in planning HSCT development in the region.

Objectives: Bacterial bloodstream infections (BSIs) with resistant pathogens in patients with haematological malignancies are rising due to increased use of novel chemotherapeutic agents and prophylactic antibiotics. Our goal was to understand the epidemiology and resistance patterns of bacterial pathogens in patients with haematological malignancies to help tailor empirical antibiotics and to limit resistance. Methods: This was a retrospective chart review looking at bacterial BSI episodes between 2007–2017 in patients previously diagnosed with haematological malignancy at a tertiary-care centre in Lebanon. Results: Among 165 hospitalised patients with haematological malignancy and bacterial BSI over 10 years, Gram-negative bacteria (GNB) caused 65.0% of all episodes, with the most common pathogens being Escherichia coli (45.6%), 79.6% of which were ESBL-producers, Pseudomonas aeruginosa (7.5%) and Acinetobacter baumannii (4.0%). The majority of the organisms (61.0%) were multidrug-resistant (MDR), with ANC < 100 neutrophils/μL (OR = 0.12, 95% CI 0.03–0.54) identified as an independent marker for increased multidrug resistance. The risk factors associated with increased mortality included recent use of amikacin (p

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.

Recurrent genetic abnormalities confer distinct morphologic features and play a role in determining the clinical behavior, prognosis and adequate treatment of acute leukemia. In the MENA region, only one study targets the frequency of genetic modifications in AML, reporting a higher occurrence of acute promyelocytic leukemia in Lebanon. Determining the frequency of translocations and gene mutations in acute myeloid and lymphoid leukemia cases in an adult patients' population in Lebanon and comparing the resultant genetic profile with the published international molecular profile of adult acute leukemia. Laboratory results of adult patients diagnosed with AML or ALL presenting to AUBMC for genetic profiling between years 2006 until June 2016 were reviewed. Genetic profiling of AML cases in our CAP accredited molecular diagnostics laboratory consists of a validated lab developed RT-PCR for the detection of RUNX1/RUNX1T1, CBFB/MYH11, KMT2A/MLLT3, PML-RARA, and BCR-ABL and mutations in the FLT3 receptor, NPM1, c-kit and CEPBA genes. The ALL panel tests for the presence of BCR-ABL1, ETV6/RUNX1; KMT2A/AFF1, and TCF3-PBX1. We reviewed 580 AML and 175 ALL cases. In the AML cohort, the M:F ratio was 1.3:1 with a mean age of 50 years. t(15;17) was present in 7.6%, t(8;21) in 4.2%, inv(16) in 3.7%, t(9;22) in 2.2% and t(9;11) in 1.7% of cases. FLT3 mutation (ITD or TKD) was present in 25.2% of all cases and 30.1% of Cytogenetics-normal (CN) patients. Mutations of the NPM1 gene was present in 31.4% of AML cases and in 43.8% of CN patients. Double positive (NPM1+/FLT3+) cases accounted for 20% of NK patients. CEBPA and c-kit mutations were detected in 7.3% and 2.4% respectively. In the ALL cohort, the mean age was 37 years. B- and T-lymphoblastic leukemia constituted 84.6% and 15.4% of ALL cases and the M:F ratio was 1.2:1 and 2.86:1 respectively. B-ALL patients were positive for t(9;22) in 14.2%, t(4;11) in 5.4%, t(1;19) in 2.7% and t(12;21) in 1.4%. T-ALL patients were negative for translocations found in our ALL panel. A lower mean age was found in our adult leukemic Lebanese population as compared to the Western cases. Other interesting findings were the lower percentage of inv(16), lower incidence of TCF3-PBX1, and the mild increase in Philadelphia positivity in our AML cohort. In our ALL cohort, t(9;22) positivity was less than expected for adult lymphoblastic leukemia. Full molecular profiling by next generation sequencing is required for further classification of cases into prognostic categories. This study will be a baseline reference for future research and epidemiological data useful for transplant centers and oncologists both in Lebanon and the region.

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.

BackgroundThe Coronavirus Disease 2019 (COVID-19) was declared a pandemic by WHO in March 2020. The first case of COVID-19 was identified in Lebanon on the 21st of February 2020, amid a national economic crisis. As the numbers of cases increased, ICU admissions and mortality rose, which led hospitals across Lebanon to take certain safety measures to contain the virus. The Naef K. Basile Cancer Institute (NKBCI) at the American University of Beirut Medical Center handles oncology outpatient visits and outpatient treatment protocol infusions. The aim of this study is to evaluate the efficacy of the safety measures put forth by the NKBCI early in the pandemic.MethodsOncology patients are amongst the immunosuppressed population, who are at greatest risk of contracting COVID-19 and consequently suffering its complications. In this manuscript, we evaluated the precautionary measures implemented at the NKBCI of AUBMC from March 1st to May 31st of 2020, by surveying oncology patients on the telephone who had live and virtual appointments in both the oncology outpatient clinics and infusion unit. We conducted a prospective study of 670 oncology patients who had appointments at the NKBCI during this period and used their answers to draw responses about patient satisfaction towards those safety measures.ResultsOur results involved 387 responses of oncology patients who visited the NKBCI during the period of March 1st to May 31st of 2020. 99% of our respondents gave a rating of good to excellent with these new measures. The option of online consultation was given to 35% in the hematology group compared to 19% in those with solid tumors (p=0.001). From the total, 15% of patients opted for the telemedicine experience as a new implemented strategy to provide patient-centered medical care. Of this group of patients, 22% faced problems with connectivity and 19% faced problems with online payment.ConclusionNKBCI was competent in following the WHO guidelines in protecting the oncology patient population. Feedback collected from the surveys will be taken into account by the committee of the NKBCI to develop new safety measures that can better control viral spread while providing patient-centered medical care.

Context Purine analogue therapy remains the standard of care in hairy cell leukemia (HCL) management. Despite high remission rates, many patients subsequently relapse and require re-treatments. Objective The aim of this study is to compare the effectiveness and safety of cladribine vs. cladribine followed by rituximab consolidation as first-line therapy of HCL. Design This is a retrospective study including all consecutive patients with classical HCL treated and followed at the American University of Beirut Medical Center (AUBMC) between 2000 and 2019. Methods We identified 29 HCL patients, with a median age of 50.5 (range: 30–71) years. Patients were divided into two cohorts based on treatment received: cohort A (N=14) received cladribine 5.6 mg/m2 intravenously (IV) for 7 days as a single agent, and cohort B (N=15) received the same dose of cladribine followed by rituximab 375 mg/m2 IV weekly for eight doses. Rituximab consolidation was given after a median time of 33 days (17–60 days) from cladribine completion. Complete remission rates were 64% and 100% in cohorts A and B, respectively. In cohort A, seven (50%) patients relapsed after a median duration of 48 months (range: 1–209 months), requiring second-line treatment with cladribine followed by rituximab. In cohort B, no relapses occurred. After a median follow up of 67 months (range: 1–227 months), the 5-year disease-free survival was significantly better in group B (100%) compared to group A (58%) (HR=0.16, 95% CI: 0.032–0.84, p=0.03). There was no significant difference in overall survival between the two groups. Grade 3/4 adverse events were observed in 92%% and 80% of patients in cohorts A and B, respectively, mainly neutropenia (78.5% vs 66.6%) and febrile neutropenia (71% vs. 40%). One patient in cohort B who received rituximab consolidation too early (day 17) died from febrile neutropenia and septic shock. Conclusion Consolidation rituximab after cladribine in frontline treatment of classical HCL showed high response rate of 100% and translated into a significant improvement in disease-free survival. Cladribine followed by rituximab consolidation may be considered as standard first-line therapy of HCL.

We compared transplant outcomes of 708 acute myeloid leukemia (AML) patients receiving haploidentical allogeneic hematopoietic-cell transplantation using thiotepa/busulfan/fludarabine (TBF) conditioning with posttransplant cyclophosphamide (ptCy), to 2083 patients receiving matched unrelated donor (MUD) transplantation using fludarabine/busulfan (FB) conditioning and in vivo T-cell depletion. For intermediate cytogenetic risk AML transplanted in first complete remission (CR1), multivariate analysis revealed that haplo-TBF significantly increased nonrelapse mortality (NRM) (HR 2.1; p = 0.0006) but did not affect relapse incidence (RI), leukemia-free survival (LFS), overall survival (OS), or graft-versus-host disease-free, relapse-free survival (GRFS). For high cytogenetic risk AML transplanted in CR1, haplo-TBF significantly increased NRM (HR = 2.7; p = 0.02), decreased RI (HR = 0.45; p = 0.03) but had no influence on LFS, OS, or GRFS. For AML transplanted in CR2, haplo-TBF significantly increased NRM (HR = 2.36; p = 0.008), decreased RI (HR = 0.38; p = 0.005), but had no influence on LFS, OS, or GRFS. Finally, for AML patients transplanted with active disease, haplo-TBF had no influence on transplant outcomes. In conclusion, compared to MUD-FB, haplo-TBF increased NRM, reduced RI in high-risk AML in CR, resulting in similar LFS, OS, and GRFS. These results comparing two different approaches support the use of a haploidentical family donor for high-risk AML patients lacking a matched sibling donor.

The regular administration of intrathecal chemotherapy has significantly reduced the risk of central nervous system leukemia in patients with acute lymphoblastic leukemia. We report the case of 28-year-old man who developed intrathecal methotrexate induced myelopathy; a rare but serious side effect of intrathecal chemotherapy. In the light of absent effective treatment strategies, description of the case, along with reviewing similar cases published in the literature will help shed a light on the possible pathophysiologic mechanisms behind this injury. To this date, there are no specific clinical, biochemical and imaging signs that would allow timely detection of intrathecal methotrexate induced myelopathy. This in turn is causing delayed treatment of this injury, resulting in significant morbidity and mortality.

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.

Relapse is the main cause of mortality in patients with acute myeloid leukemia (AML) after allogeneic hematopoietic stem cell transplantation (allo-HSCT). Adverse cytogenetic or molecular risk factors, as well as refractory disease or persistent measurable residual disease (MRD) at the time of transplantation are associated with an increased risk of recurrence. Salvage therapy for AML relapse after allo-HSCT is often limited to chemotherapy, donor lymphocyte infusions and/or second transplants and is rarely successful. Effective post-transplant preventive intervention in high risk AML may be crucial. The most frequent and promising approach is the use of post-transplant maintenance with hypomethylating agents or with FLT3 tyrosine kinase inhibitors when the target is present. Moreover, IDH1/IDH2 inhibitors and BCL-2 inhibitors in combination with other strategies are promising approaches in the maintenance setting. Here we summarize the current knowledge about the preemptive and prophylactic use of pharmacologic agents after allo-HSCT to prevent relapse of AML.

Background: Immunotherapy agents offer novel treatment options in advanced cancers. However, their use is limited in developing countries lacking unifying guidelines and can be followed by a financial burden. In this study, we aimed to provide an overview regarding the use of immunotherapy and the overall response to treatment in patients with metastatic disease in relation to cost-effectiveness. Methods: This was a retrospective study involving adult metastatic cancer patients, treated with programmed cell death-1 (PD-1) inhibitors at American University of Beirut Medical Center (AUBMC), a tertiary cancer center in Lebanon. Study enrollment began on January 1, 2014 and ended on January 12, 2016. Baseline demographics, epidemiological and clinical data were collected from the patients' records. Results: Our study consisted of 34 patients. Fifteen patients self-financed the treatment. The patients were prescribed immunotherapy without programmed cell death-ligand 1 (PD-L1) testing as it was not part of the guidelines at the time. Twenty-two patients were treated with nivolumab and 12 patients with pembrolizumab. Thirteen patients showed partial response or stable disease, while 21 patients showed progression. Conclusion: Improvement in terms of overall survival and progression-free survival has been undercut by the lack of availability of these drugs and their cost. Considering that a large percentage of patients do not respond to immunotherapy, there is a need to use guidelines such as a preset PD-L1 level that ensure cost-effectiveness and prevent resource waste. World J Oncol. 2020;11(4):150-157 doi: https://doi.org/10.14740/wjon1277

Brentuximab Vedotin (BV) is a chimeric anti-CD30 antibody, conjugated to anti-tubulin mono-methyl-auristatin. The AETHERA trial revealed increased PFS when BV is used as maintenance therapy for 16 cycles in high risk Hodgkin lymphoma (HL) after autologous stem cell transplantation (ASCT). However, this schedule is associated with high cost and significant toxicity. Our objective is to assess the safety and efficacy of four cycles Brentuximab Vedotin as consolidation after ASCT for relapsed/refractory (R/R) HL. We identified 20 consecutive adult patients with R/R HL treated with BV for four cycles as consolidation after ASCT. The indications for BV consolidation included primary refractory disease in 12 patients (60%), early relapse in 6 patients (30%) and extra-nodal involvement in two patients (10%). After a median follow up of 27 months, five (25%) patients relapsed. The median time to relapse was 6 months. Median PFS and OS were not reached. No significant toxicities were reported.

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

BACKGROUND: The treatment of patients with Hodgkin lymphoma (HL) who develop disease progression after undergoing allogeneic stem cell transplantation (allo‐SCT) remains challenging. METHODS: The authors assessed outcomes in 184 adult patients with HL who developed disease recurrence or progression after a matched related or unrelated allo‐SCT at European Society for Blood and Marrow Transplantation–participating centers between 2010 and 2014. RESULTS: Eighty patients who received brentuximab vedotin (BV) salvage therapy were compared with 104 patients who did not. Patients in the BV group were younger (median age of 30 years vs 34 years) and were more likely to receive pretransplant BV (65% vs 46%) or posttransplant donor lymphocyte infusion (66% vs 33%). The 2 groups otherwise were comparable. Patients in the BV group received a median of 6 doses of posttransplant BV, resulting in a complete remission rate of 29%, a partial response rate of 45%, and a stable disease rate of 26%. Response to BV after allo‐SCT did not appear to be affected by receipt of pretransplant BV. Despite a longer median follow‐up for surviving patients in the BV group (33 months vs 23 months; P

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.

Dynamics of molecular response in AML patients with NPM1 and FLT3 mutations undergoing allogeneic stem cell transplant

BACKGROUND Sorafenib has shown encouraging results in patients with Fms-like tyrosine kinase 3 (FLT3)-positive acute myeloid leukemia. Its role after allogeneic stem cell transplantation (HSCT) has been reported in a few cases with encouraging results. METHODS The authors describe the use of sorafenib as a maintenance agent after HSCT in 27 patients with FLT3-positive acute myeloid leukemia. RESULTS The median age of the patients was 46 years (range, 15-57 years). Sorafenib was introduced at a median of 70 days (range, 29-337 days) after HSCT. The median treatment duration was 8.4 months (range, 0.2-46 months). Eleven patients experienced treatment toxicities, mainly of grade 1 to 2 (graded according to the National Cancer Institute Common Toxicity Criteria [version 4.0]). Dose reduction or withdrawal was required in 4 patients and 4 patients, respectively. The persistence of toxicity prompted treatment withdrawal in 1 patient. Clinical improvement followed dose modifications. Thirteen patients experienced chronic graft-versus-host disease (limited in 9 patients and extensive in 4 patients), resulting in dose reduction in 5 patients followed by withdrawal in 1 of these individuals. At a median follow-up of 18 months (range, 4-48 months), 25 patients were alive (all of whom were in complete molecular remission) and 18 were still receiving treatment, with 1-year overall survival and progression-free survival rates of 92% ± 6% and 92% ± 5%, respectively. CONCLUSIONS Sorafenib treatment after HSCT appears to be feasible and highly effective with dose individualization according to patient tolerability. Further analysis is needed to evaluate the immunomodulating role of sorafenib after HSCT. The data from the current support prospective controlled trials of sorafenib after HSCT. Cancer 2017;123:2867–74. © 2017 American Cancer Society.

Low-dose 5-azacytidine as preventive therapy for relapse of AML and MDS following allogeneic HCT

Background: Intensified immunochemotherapy with rituximab, doxorubicin, cyclophosphamide, vindesine, bleomycin, and prednisone (R-ACVBP) has been shown to improve outcomes in younger adults with high-grade B-cell lymphomas (hg-BCL) when compared to standard therapy with R-CHOP (Cyclophosphamide-Adriamycin-Vincristine-Prednisone) (Recher C. Lancet 2011). Due to unavailability of vindesine at our institution, we primarily aimed at assessing the safety and efficacy of replacing vindesine with vincristine in a modified R-ACVBP protocol (mR-ACVBP). Secondary endpoints included progression-free survival (PFS), and overall survival (OS). Methods: This is a retrospective study performed at the American University of Beirut Medical Center (AUBMC), Lebanon, including all consecutive adult patients (pts) with newly diagnosed hg-BCL who received first-line mR-ACVBP from 10/2014 to 10/2019. mR-ACVBP protocol was similar to published original protocol with the exception of vindesine being replaced by vincristine 1.5 mg intravenously on days 1 and 5 of each cycle (initial protocol included vincristine 2 mg on days 1 and 5, later adjusted for toxicity). Pts were assessed for response after 4 cycles of mR-ACVBP. Responders continued with consolidation consisting of 2 cycles of high-dose methotrexate followed by 4 cycles of Rituximab-Ifosfamide-Etoposide then low-dose cytarabine x2. Pts with inadequate response on interim imaging were offered consolidative autologous stem cell transplantation (ASCT). Incomplete responders after 4 cycles (CR defined as delta SUVmax more than 70%) were shifted to salvage therapy including R-ICE (Rituximab, Ifosfamide, Cytarabine, Etoposide), or R-DHAP (Rituximab, Dexamethasone, Cytarabine, Cisplatin). Pts with age-adjusted IPI ≥ 2 could receive consolidative ASCT at the physician's discretion. Results: We identified 56 pts with hg-BCL, with a median age of 41 years [range: 21-67]. 64% of patients were males. 45 (80%) pts had advanced stage (III/IV), and 37 (66%) pts had an age-adjusted-IPI score >1. Fifty-one pts were evaluable for response after 4 cycles by PET CT scan. The overall response rate was achieved in 46 (90%) pts; complete response (CR) in 41 (80%), partial response (PR) in 5 (10%), 2 of which considered to have inadequate response as per delta SUVmax. 12 (27%) pts received consolidative ASCT, 27 (61%) continued consolidation chemotherapy, and 5 (11%) pts received subsequent salvage treatment. The most common reported treatment emergent adverse events, encountered during induction mR-ACVBP, were anemia (n=51, 91%), followed by febrile neutropenia (n=36, 64%, grade 4 in 26 (46%) pts, of whom four required intensive care monitoring), thrombocytopenia (n=22, 39%), and mucositis (n=12, 21%). Peripheral neuropathy was encountered in 7 (12%) pts (grade 1, n=2, grade 2, n=4, grade 3, n =1). Two deaths were attributed to treatment due to febrile neutropenia and septic shock during first and third cycle of mR-ACVBP in patients who had an aaIPI of 3. After a median follow up of 17 months [range, 0.5-55], a total of 4/44 (9%) pts progressed, 3 while on treatment after high-dose methotrexate, 1 after therapy completion. The median PFS and OS were not reached. The 2-year PFS and OS were 86% and 87% respectively. At last follow up, 47 pts were alive (44 (94%) pts were in continuous CR, 1 (2%) pt in PR and 2 (4%) pts progressive disease), 6 pts died, and 3 were lost to follow up. Conclusion: The use of vincristine in mR-ACVBP instead of vindesine seems to be feasible, with acceptable manageable adverse events. Despite higher risk disease, survival rates seem to be comparable to published data of the original R-ACVBP protocol. Disclosures No relevant conflicts of interest to declare.

Salvage chemotherapy and autologous stem cell transplantation (auto-SCT) results in the cure of around 50% of patients with Hodgkin lymphoma (HL) failing first line therapy. In historical data, patients who progressed after auto-SCT had a poor outcome, with a median overall survival (OS) of around 1-2 years. Significant progress has been achieved in the last decade with the use of brentuximab vedotin (BV) or check-point inhibitors (CPI) and the increasing use of haploidentical transplant. However, little information is available about the characteristics and real-world outcomes of patients with HL relapsing after auto-SCT in the current era. To assess prognosis of patients with recurrent-HL post auto-SCT over time, we analyzed the European Blood and Marrow Transplant registry data of 1781 adult HL patients who relapsed between 2006 and 2017 after a first auto-SCT. A specific questionnaire was sent to all participant centers to obtain additional data regarding characteristics of the patients, treatment of relapse and outcome after auto-SCT failure. Detailed data were collected for 760 patients [median age 32; interquartile range (IQR) 25-42] included in this study. After a median follow-up for alive patients of 57 months (IQR: 29-89), the 4-year OS after relapse for the 760 included patients was 46% (95%CI: 43-50) and similar to that of 1021 non-included patients (45%, 95%CI: 41-48). The 4-year OS after relapse continuously increased from 35% (95%CI: 27-45) for 136 patients relapsing in 2006-2008, to 43% (95%CI: 37-49) for 258 patients relapsing in 2009-2011, 49% (95%CI: 43-56) for 238 patients relapsing in 2012-2014, and 61% (95%CI: 52-72) for 128 patients relapsing in 2015-2017 (p=0.001) (Figure 1). Improvement over time was predominantly noted in patients who had an early relapse (within 12 months) after auto-SCT (p=0.01) but not in those with a late relapse (p=0.6). On multivariate analysis, patients who relapsed in more recent years and those with a longer interval from transplant to relapse had a better OS, whereas increasing age, poor performance status at relapse, bulky disease at relapse, extranodal disease at relapse and presence of B-symptoms at relapse were associated with a worse OS. Regarding treatment at relapse, BV was used in 233 patients (31%) after a median of 2 months from relapse (IQR: 0.8-8), predominantly as first treatment of relapse (155 patients). BV use increased over the 4 time periods from 3% to 19%, 49% and 49% respectively, and resulted in a complete remission (CR) in 46% and a partial response (PR) in 32%. The 4-year OS from BV use for relapse after auto-SCT was 56% (95%CI: 49-64). CPI were used in 91 patients (12%) including nivolumab in 75 patients and pembrolizumab in 12 patients after a median of 18 months from relapse (IQR: 5-35). CPI use increased over the 4 time periods from 1% to 4%, 14% and 35% respectively, and resulted in a CR of 44%, PR 32%, with a 4-year OS from CPI use of 44% (95%CI: 30-63). Finally, a second SCT (SCT2) was performed in 330 patients (43%) predominantly allogeneic SCT (285 patients, 86%) including a haploidentical SCT in 54 patients (16%). SCT2 was performed in 40% and 37% of patients relapsing in 2006-2008 and 2009-2011 respectively but its use increased to 49% and 51% of patients relapsing in 2012-2014 and 2015-2017 respectively. Four-year OS after SCT2 was 55%. In conclusion, outcome after post-transplant relapse has improved significantly in recent years, particularly in the case of early relapse, possibly reflecting, among other factors, the efficacy of post-transplant salvage including BV, CPI and second transplant. These large-scale real-world data can serve as benchmark for future studies in that setting. Figure 1 Disclosures Blaise: Jazz Pharmaceuticals: Honoraria. Sureda Balari:Incyte: Consultancy; Celgene: Consultancy, Honoraria; BMS: Speakers Bureau; Roche: Honoraria; Sanofi: Consultancy, Honoraria; Novartis: Consultancy, Honoraria; Gilead/Kite: Consultancy, Honoraria; Merck Sharpe and Dohme: Consultancy, Honoraria, Speakers Bureau; Celgene/Bristol-Myers Squibb: Consultancy, Honoraria; Takeda: Consultancy, Honoraria, Speakers Bureau; Janssen: Consultancy, Honoraria.

Background Allogeneic stem cell transplantation is a potentially curative therapy for patients with acute myeloid leukemia (AML) after achieving complete remission (CR). The aim of this study is to evaluate the optimal dose of thiotepa, administered as part of the thiotepa-busulfan-fludarabine (TBF) conditioning regimen for allogeneic stem cell transplantation in adults with AML in CR. Patients and Methods In a retrospective multicenter analysis, we identified 240 patients allotransplanted from matched related or unrelated donors or T replete haplo-identical donors. We compared the transplantation outcomes of patients who received 5 mg/kg thiotepa and 2 days of intravenous busulfan at 6.4 mg/kg (T1B2F) versus those who received 10 mg/kg thiotepa with 2 days of intravenous busulfan at 6.4 mg/kg (T2B2F). The median follow-up was 20 months. Results On univariate analysis, the incidence of acute graft versus host disease (GVHD) grade II to IV was significantly lower in the T1B2F group (19%) versus 32% in the T2B2F group (P = .029). This result was confirmed on multivariate analysis; acute GVHD was higher for patients receiving T2B2F (hazard ratio, 2.22; P = .024). No significant change in non-relapse mortality, progression-free survival, or overall survival was observed between the 2 groups. Conclusion T2B2F is associated with a higher incidence of acute GVHD compared with T1B2F. These results suggest that a lower dose-intensity of thiotepa and busulfan in the TBF regimen may yield better results in patients with AML in CR.

Severe neutropenia remains among the most common complications associated with hematological diseases and their treatment, especially in the early poststem cell transplantation. Managing life-threatening infections associated with prolonged and profound neutropenia thus remains an essential component for the optimal care of patients undergoing transplant. Several therapeutic interventions have been attempted either to limit the duration of neutropenia through granulocyte colony stimulating factors (GCSF), or to treat associated infections through the use of granulocyte transfusions. The efficacy and safety of granulocyte transfusions have been controversial, and the conflicting results reported by several trials can be explained by the significant variability related to patient selection, timing of initiation, and duration of transfusions, preparation methods among multiple others. We herein report a case of life-threatening necrotizing fasciitis post haploidentical stem cell transplant, responding to the combination of antibiotics and daily transfusions of non-irradiated GCSF stimulated leukocytes from healthy donors without surgical intervention. We also provide a concise review of the available literature regarding the use of this intervention, its efficacy and safety and comparison of irradiated with non-irradiated transfusions.

Background Most studies addressing the impact of hematopoietic stem cell transplantation (SCT) on pulmonary function test (PFT), and the various factors affecting that impact have been performed on the allogenic type. Few have addressed PFT changes in autologous SCT. This study describes PFT changes seen in autologous SCT recipients and addresses the various factors impacting these changes. Patients and Methods We reviewed the medical records of 223 consecutive adult autologous SCT recipients. We collected pre-transplant and post-transplant data, as well as PFT data and long-term mortality. Results A total of 123 patients with lymphoma receiving the BEAM (carmustine, etoposide, aracytin, and melphalan) conditioning regimen had a significant 5% drop in mean forced vital capacity and total lung capacity but no significant change in forced expiratory volume in one second/forced vital capacity ratio nor in diffusion lung capacity of carbon monoxide adjusted to volume. Fifteen percent of the patients with lymphoma had a clinically significant drop of 15% in their lung volume parameters. The patients with multiple myeloma receiving the melphalan conditioning regimen had no significant change in any of the PFT parameters. Smoking, baseline PFT parameters, and radiation did not affect lung function or mortality. Conclusions Autologous SCT impact on lung function depends on the disease and conditioning regimen. It leads to a drop in lung volumes but no obstruction or decrease in diffusion in patients with lymphoma receiving the BEAM regimen. Autologous SCT did not affect lung functions in patients with multiple myeloma, and these patients may not need screening PFTs.

Acute myeloid leukemia (AML) with FLT3-mutation carries a poor prognosis, and allogeneic stem cell transplantation (allo-SCT) is recommended at first complete remission (CR1). We assessed 462 adults (median age 50 years) with FLT3-mutated AML allografted between 2010 and 2015 from a matched related (40%), unrelated (49%), or haploidentical donor (11%). The median follow-up of alive patients was 39 months. Day-100 acute graft versus host disease (GVHD) grades II-IV and III-IV were encountered in 26% and 9%, whereas the 2-year incidence of chronic and extensive chronic GVHD were 34% and 16%, respectively. The 2-year incidences of relapse and nonrelapse mortality were 34% and 15%, respectively. The 2-year leukemia-free survival, overall survival (OS), and GVHD relapse-free survival (GRFS) were 51%, 59%, and 38%, respectively. In multivariate analysis, NPM1-mutation, transplantation in CR1, in vivo T-cell depletion, and posttransplant sorafenib improved OS, whereas more than one induction (late CR1) negatively affected OS. Similarly, NPM1-mutation, a haploidentical donor, T-cell depletion, and sorafenib maintenance improved GRFS, whereas late CR1 or persistent disease negatively affected it. In conclusion, FLT3-mutated AML remains a challenge even following allo-SCT. In vivo T-cell depletion and posttransplant sorafenib significantly improve OS and GRFS, and may be considered as standard of care. ispartof: Clin Hematol Int vol:1 issue:1 pages:58-74 ispartof: location:United States status: Published online

Background: Patients diagnosed with acute myeloid leukemia (AML) with Fms-like tyrosine kinase 3 (FLT3) mutations have a very poor prognosis, despite use of allogeneic hematopoietic stem cell transplantation (allo-HSCT) and salvage treatments. Patients and Methods: We previously reported the safety and efficacy of sorafenib, an FLT3 inhibitor, as a maintenance agent after allo-HSCT in patients diagnosed with AML with FLT3 mutations. We provide an update on the 27 patients with FLT3-mutated AML in our original report, who received sorafenib as a single maintenance agent. Results: Since our previous report, others have confirmed our reported significant overall survival and progression-free survival in patients who received sorafenib before and/or after allo-HSCT. In this update on the 27 patients with FLT3-mutated AML in our original report, we show persistence of the previously reported impressive long-term disease control. Conclusion: Our results, with longer follow-up than in our previous report, together with those of others, further support the use of sorafenib as a maintenance agent after allo-HSCT. Patients with acute myeloid leukemia (AML) with Fms-like tyrosine kinase 3 (FLT3) mutations have a very poor prognosis, despite use of allogeneic hematopoietic stem cell transplantation (allo-HSCT) and salvage treatments. We previously reported the safety and efficacy of sorafenib, as a maintenance agent after allo-HSCT in 27 patients with FLT3-mutated AML. We provide an update on the patients in our original report, who received sorafenib as a single maintenance agent, and show persistence of the previously reported impressive long-term disease control. Our results continue to support the use of sorafenib as a maintenance agent after allo-HSCT.