BackgroundAutologous stem cell transplantation (ASCT) is a potentially curative treatment for several hematologic malignancies. However, the short-term cardiotoxic effects of conditioning regimens remain underexplored. This study evaluates echocardiographic changes occurring within the first 100 days after ASCT.MethodsWe conducted a retrospective single-center study of 205 lymphoma and Multiple Myeloma patients who underwent ASCT at the American University of Beirut Medical Center (AUBMC) between 2013 and 2022. Echocardiographic parameters before ASCT were compared to those obtained 100 days post-transplant. Conditioning regimens for the lymphoma patients included BEAM (carmustine, etoposide, cytarabine, and melphalan), however for the Multiple Myeloma patients, high-dose melphalan (200 mg/m2), and other chemotherapy-based regimens. Primary outcomes were changes in left ventricular ejection fraction (LVEF) and the incident of new valvular disease. Statistical analyses included paired t-tests, McNemar's test, and chi-square tests.ResultsAmong 205 patients, 97 (47.3%) had partial remission at transplantation, and 176 (85.9%) had no prior left ventricular (LV) dysfunction. A total of 108 (52.7%) received myeloablative BEAM conditioning. Pre-ASCT, 193 (94.1%) patients had LVEF >50%, compared with 187 (91.2%) at 100 days post-ASCT (p = 0.286). The mean LVEF showed a modest but statistically significant decline (p = 0.016). The prevalence of valvular abnormalities increased from 86 (42%) to 104 (50.7%) post-ASCT (p = 0.073). Pre-existing LV dysfunction was significantly associated with both post-transplant LV dysfunction and valvular disease (p = 0.018 and p < 0.05, respectively). Male gender was associated with a higher incidence of valvular disease (p = 0.024). Conditioning intensity, malignancy type, and prior valvular disease were not significantly correlated with cardiac outcomes. Interestingly, 12 patients with baseline LVEF <50% experienced no cardiac events or ICU admissions post-ASCT; 9 of these demonstrated improved LVEF at follow-up.ConclusionsASCT is associated with mild but statistically significant early declines in LVEF and increased valvular abnormalities within 100 days post-transplant. Early post-ASCT echocardiographic surveillance may enable the detection of subclinical cardiotoxicity. Prospective longitudinal studies are warranted to define the long-term cardiac impact of ASCT and its conditioning regimens.
The European Group for Blood and Bone Marrow transplantation Practice Harmonization and Guidelines Committee together with the Lymphoma Working Party convened 23 experts in Hodgkin lymphoma, transplantation, and radiation oncology, to develop consensus recommendations on the use of autologous and allogeneic haematopoietic cell transplantation (HCT) in relapsed or refractory Hodgkin lymphoma. Through a structured literature review and a 2-day workshop in Berlin, Germany, on Sept 29 and 30, 2025, the panel established guidance across major clinical decision points. The outcome of this review and workshop include the following recommendations. Salvage therapy should include brentuximab vedotin or checkpoint inhibitors, or both, with metabolic complete response preferred before autologous HCT. BEAM (carmustine, etoposide, cytarabine and melphalan) remains the most commonly used conditioning regimen, and autologous HCT continues to be the standard for chemosensitive relapse. Peri-transplantation radiotherapy could be considered for PET-positive or residual disease. Brentuximab vedotin consolidation is recommended for patients at high-risk. Allogeneic HCT is advised for eligible patients who relapse after autologous HCT, ideally with reduced intensity conditioning and post-transplantation cyclophosphamide as graft-versus-host disease prophylaxis. Routine maintenance after allogeneic HCT is not recommended; relapse management should be tailored and can involve donor lymphocyte infusion, brentuximab vedotin, checkpoint inhibitors, chemotherapy, radiotherapy, or clinical trial enrolment.
Purpose : The combination of cladribine (CLAD), low-dose cytarabine (LDAC), and venetoclax (CLAD-LDAC-venetoclax) has demonstrated promising efficacy in acute myeloid leukemia (AML) but remains underutilized globally. Since 2020, this regimen has been implemented at the American University of Beirut Medical Center (AUBMC) for patients ineligible for intensive chemotherapy. Patients and Methods : This study evaluates its efficacy and safety in newly diagnosed and relapsed/refractory (R/R) AML. We retrospectively analyzed consecutive AML patients treated with CLAD-LDAC-venetoclax between January 2020 and September 2024. Treatment consisted of cladribine (5 mg/m²/day, 5 days), LDAC (20 mg subcutaneously twice daily, 10 days), and venetoclax (100 mg daily with azole antifungal co-administration). Outcomes are overall response rate (ORR), including complete remission (CR), and CR with incomplete hematologic recovery (CRi), event-free survival (EFS), overall survival (OS), and safety. Results : Among 19 frontline patients (median age: 67 years), the ORR was 88% (CR/CRi: 76%/12%), with 47% undergoing allogeneic hematopoietic cell transplantation (allo-HCT). Median EFS was 13.4 months, OS was 35.3 months, and 2-year OS was 58%. In 14 R/R AML patients (all venetoclax-pretreated), ORR was 57% (CR/CRi: 29%/21%), with a median EFS of 2 months and OS of 5.2 months. In both cohorts, infection rates were increased, especially in secondary AML. Conclusion : CLAD-LDAC-venetoclax was highly effective in newly diagnosed AML, but had limited response durability in the R/R setting, particularly post-venetoclax exposure. These findings support its role as an induction strategy for unfit patients and highlight the need for novel salvage approaches in R/R AML.
Haploidentical hematopoietic stem cell transplant (Haplo-HSCT) has emerged as an alternative for patients lacking matched human leukocyte antigen (HLA) donors. The scarcity of stem cell donor registries and cord banks across the Eastern Mediterranean (EM) region has led to increased need of Haplo-HSCT as a mean to overcome this limitation. In this study, we aimed to assess trends in Haplo-HSCT utilization within the Eastern Mediterranean Blood and Marrow Transplantation (EMBMT) registry from 2012 to 2024, and describe key clinical and transplant-related factors associated with patient outcomes. We conducted a retrospective, multicenter registry-based analysis of patients who had their first un-manipulated Haplo-HSCT in ten EMBMT centers across six countries, who responded and accepted to participate in the study. Due to the variability in time-to-event reporting across different centers, survival and relapse-related outcomes were analyzed descriptively. Continuous variables were summarized using medians and ranges, and categorical variables were described by counts and percentages. The association between individual baseline variables and patient survival, was conducted using a univariate analysis utilizing the chi-square test. Categorical variables such as patient and transplant characteristics were compared against survival status at last follow-up. All variables were further evaluated in the multivariate analysis. Overall survival (OS) and progression-free survival (PFS) were estimated using Kaplan-Meier survival analysis. Between 2012 and 2024, a total of 673 patients received haplo-HSCT across ten centers, in six EMBMT-registered countries. Median age was 25 years, and the predominant indication for haplo-HSCT was leukemia (64.3%). Transplant was done using stem cells collected from peripheral blood in majority of cases (65.7%), and Total Body Irradiation (TBI) was utilized in 37.6% of all patient. 76.5% had malignant hematological disorders, while 23.5% had non-malignant disorders. Relapse was reported in 232 patients (34.5%) and death in 220 patients (32.7%). Of these, 88 deaths (12.8%) were attributed to disease progression. Haplo-HSCT activity increased steadily over the study period, with a marked increase in the last few years, reflecting broader regional adoption. PFS was 66% and 60% at 1- and 2- years after transplantation. Also, the 1-year and 2-year post-transplant OS was 71% and 65%, respectively. Multivariate analysis identified disease type and chronic GVHD as factors associated with improved outcomes. Despite variability across centers, outcomes were consistent with international benchmarks, underscoring the growing feasibility and therapeutic value of haplo-HSCT in the EMRO region. Haplo-HSCT is increasingly adopted across the EMRO region as the primary alternative donor HSCT modality. Our findings confirm its clinical efficacy, with outcomes comparable to international benchmarks. These results underscore the importance of continued regional collaboration and the development of personalized strategies to address challenges such as graft-versus-host disease (GVHD), disease relapse, and disparities in access to transplantation services.
Total body irradiation (TBI) is a form of radiotherapy that provides a uniform dose of ionizing radiation to the entire body. It has been a mainstay of the conditioning regimen for allogeneic hematopoietic stem cell transplantation (allo-HSCT) for many decades. The clinical usefulness of TBI is based on the balance of its cytotoxic and immunosuppressive effects, which allow for the eradication of remaining malignant cells, including sanctuary sites, as well as the establishment of a successful transplant. Early "supra-lethal" single-dose schedules of TBI were highly effective but also came with a substantial treatment-related toxicity burden. As a result, fractionated doses of TBI were developed to improve the tolerability of the regimen. Currently, TBI is used as a component of the conditioning regimen for all three types of allo-HSCT conditioning: myeloablative conditioning (MAC, typically TBI ≥ 12 Gy or equivalent), nonmyeloablative conditioning (NMA, typically TBI ≤ 2 Gy), and reduced-intensity conditioning (RIC, intermediate doses). The dose of TBI is intended to balance the efficacy of the regimen against non-relapse mortality (NRM). High doses of TBI are more effective in reducing the risk of relapse but also increase the risk of NRM, particularly in the elderly. The lowest doses of NMA, typically 2 Gy, have expanded the scope of allo-HSCT but may be insufficient for durable disease control in high-risk disease because relapse remains a major cause of failure. intermediate TBI doses (4-8 Gy) are used in reduced or intermediate-intensity platforms to enhance antileukemic activity while limiting toxicity relative to fully myeloablative regimens. It is important to note that the outcomes of the regimen are not determined by TBI dose only, but by the interaction among dose/fractionation, the chemotherapy backbone, disease status, and transplant platform. The available data suggests a need for a platform-specific dose-adapted regimen of TBI rather than a standard dose.
Allogeneic hematopoietic stem cell transplantation (allo-HSCT) is considered the best cure for many hematologic diseases, but it is associated with multiple short and long term cardiovascular adverse effects. This retrospective study assesses the short-term cardiovascular consequences after allo-HSCT and compares the risk of developing cardiotoxicity based on conditioning regimens and post-transplant prophylactic medications. A total of 310 patients were identified at the American University of Beirut Medical Center (AUBMC), of whom 255 were followed up for 100 days post-transplant. There was a significant decrease in left ventricular ejection fraction (LVEF), from a mean of 59.14% pre-transplant to 58.44% post-transplant (P= 0.037). Significant decreases were also noted in the E wave, E' wave, and E/A ratio (P <0.01, <0.001, and 0.006, respectively), while no significant changes were observed in A wave or E/E' ratio (P= 0.197 and 0.078, respectively). No significant decrease in global longitudinal strain was noted (P=0.18). Haploidentical transplants, cyclophosphamide, and sequential conditioning regimens were associated with reduced LVEF (P= 0.002, 0.007 and 0.019, respectively). Among those followed up for 100 days, 8 patients (3.2%) developed moderate or large pericardial effusion. While the average decrease in LVEF was of no clinical significance, the percentage of patients with reduced LVEF (<50%) increased from 3.1% pre-transplant to 6.7% at 100 days. These subclinical changes in LVEF and diastolic measurements are not fully understood. We recommend serial echocardiographic follow-ups to assess their potential clinical relevance and the risk of cardiotoxicity later in life, particularly those undergoing haploidentical transplant, receiving cyclophosphamide or sequential conditioning regimens.
Cancer poses significant fertility challenges for women of childbearing age, yet the adoption of fertility preservation (FP) measures remains limited. This study aimed to explore patients’ understanding, attitudes, concerns, psychological well-being, and factors influencing their decisions regarding FP during treatment. This prospective cohort study involved women aged 18 to 42 diagnosed with non-metastatic breast cancer or lymphoma, treated at the American University of Beirut Medical Center. Patients completed questionnaires at intervals over a 2- to 3-year period following diagnosis. Among the 123 women studied, 71.5
Background Preventing graft vs. host disease (GvHD) after allogeneic hematopoietic stem cell transplant (allo-HSCT) is essential to improving the outcomes and quality of life of allo-HSCT recipients. Little is known about the trends and patterns of global GvHD prevention practices. Thus, the Worldwide Network for Blood & Marrow Transplantation global GvHD project aims to understand and describe the patterns of GvHD prevention and management worldwide. This article discusses GvHD prevention practices in the East Mediterranean (EM) region. Materials and methods A questionnaire was distributed electronically to the EM region transplant centers and filled out by program directors or designees. Responses were received between December 2022 and June 2023. The questionnaire had 33 items, with 7 sections focusing on the different commonly used agents in GvHD practices (including calcineurin inhibitors, in vivo T-cell depletion, and methotrexate [MTX]). Results Thirty responses from 26 institutions were received from 11 countries in the EM region. All programs perform matched-related donor (MRD) transplants, 29 perform haploidentical transplants, and 19 perform matched unrelated donor (MUD) transplants. Cyclosporine (CsA) with MTX was the preferred regimen in both myeloablative (79%) and reduced intensity conditioning (50%). CsA was more widely used compared to tacrolimus (Tac) (93% vs. 57%). The duration of calcineurin inhibitor use before initiating taper in recipients with malignant and non-malignant disorders was similar between CsA and Tac. All programs reported routine monitoring of calcineurin inhibitor levels. Twenty-nine programs reported using MTX, administering it over 3–4 days post-HSCT. The use of different in vivo T-cell depletion therapies was commonly reported, particularly anti-thymocyte globulin (ATG) and post-transplant cyclophosphamide (PTCy). ATG use was reported by 77% and 79% of programs for MRD and MUD HCT, respectively. Additionally, most programs (97%) reported using PTCy mainly for haploidentical transplants. Among centers using PTCy, most programs reported using a dose of 50 mg/kg, and the most common schedule was Days +3 and +4. However, 12 programs reported using lower doses of 25–40 mg/kg or spaced-out schedules (Days +3 and +5). Conclusion This study describes the different practices of GvHD prophylaxis in the EM region. Our results show that allo-HSCT centers in the EM regions utilize most standard-of-care agents, and most practices are in alignment with evidence-based guidelines.
Background - Haploidentical hematopoietic stem cell transplantation (haplo-HSCT) has become an increasingly adopted curative strategy for patients with acute myeloid leukemia (AML), especially in the absence of a fully matched donor. Among conditioning regimens, thiotepa-busulfan-fludarabine (TBF) has emerged as one of the most widely used. The intensity of this regimen can be modulated by adjusting the doses of thiotepa and busulfan, potentially balancing toxicity and antileukemic efficacy. However, evidence on the optimal doses of these alkylating agents on transplant outcomes remains limited.Methods – This is a retrospective analysis based on data from the European Society for Blood and Marrow Transplantation (EBMT) registry. From 2010 to 2022, AML patients receiving a first haplo-HSCT in first or second complete remission (CR1, CR2) with a TBF-based conditioning and post-transplant cyclophosphamide (PTCy) as GVHD prophylaxis were identified. Based on busulfan dose, conditioning intensity was defined as myeloablative (TBF-MAC, ≥8.8 mg/kg busulfan) or reduced-intensity (TBF-RIC, <8.8 mg/kg). In both groups, thiotepa was considered high-dose when ≥8 mg/kg.Results – A total of 2393 patients (mean age 53.2 years) were included in the analysis, mostly transplanted in CR1 (77.6%, n=1856), with a predominance of intermediate risk AML (70.6%, n=1201). At 2-years, overall survival (OS), relapse incidence (RI), non-relapse mortality (NRM) were 65.7%, 18.7% and 21.5%, respectively. Acute graft versus host disease (aGVHD) ≥3 and extensive chronic GVHD (cGVHD) occurred in 9.1% and 10.5% of cases.TBF-RIC conditioning was administered to 1255 patients, while 1138 were treated with TBF-MAC. OS rates were 71.1% and 59.3% with NRM rates of 17.7% and 26% in the TBF-MAC and TBF-RIC group, respectively.In multivariate analysis within TBF-RIC group, high-dose thiotepa was associated with increased risk of grade ≥3 aGVHD (HR 1.95, 95% CI: 1.17-3.24, p=0.01) and cGVHD (HR 1.49, 95% CI: 1.07-2.08, p=0.018), without impact on extensive cGVHD, RI and OS.In the TBF-MAC group, high-dose thiotepa was significantly associated with increased mortality risk (HR 1.62, 95% CI: 1.05-2.52, p=0.03), primarily driven by higher NRM (HR 1.83, 95% CI: 1.01-3.33, p=0.046). Additionnaly, transplant in CR2 correlated with worse survival (HR 1.39, 95% CI: 1.04-1.86, p=0.026) and higher RI (HR 1.27, 95% CI: 1.01-1.60, p=0.045).Peripheral blood as graft source was associated with higher grade ≥2 aGVHD (HR: 1.47, 95% CI: 1.03-2.09, p=0.033) in TBF-RIC group, and grade ≥3 aGVHD (HR:1.74, 95% CI: 1.09-2.79, p=0.021) in TBF-MAC group, but did not affect OS and RI.Older age and lower Karnofsky score were significantly associated with poorer OS and higher NRM across both TBF-MAC and TBF-RIC.Conclusions – In this large retrospective analysis on patients with AML undergoing haplo-HSCT in CR1-CR2 with a TBF conditioning, thiotepa dose significantly influenced outcomes in both RIC and MAC setting. High-dose thiotepa was associated with increased risk of severe aGVHD and cGVHD when combined with RIC busulfan doses, and with higher NRM and poorer survival, when used in combination with MAC busulfan doses. Across both TBF-RIC and TBF-MAC cohorts, no advantage in terms of RI was observed with high-dose thiotepa, suggesting no added benefit in disease control. These findings indicate that lower thiotepa doses (<8 mg/kg) may be preferable, regardless of conditioning intensity. Additionnaly, among TBF-MAC treated patients, those transplanted in CR2 had higher risk of relapse and mortality. Irrespective of TBF regimen, the use of peripheral blood stem cell grafts increased aGVHD risk without affecting OS or RI, and older age and lower Karnofsky performance scores remain adverse prognostic factors for survival.
Sexually transmitted infections (STIs) are a difficult health challenge for immunocompromised patients. Patients treated for several haematological malignancies have further compromised immune systems. Furthermore, many chemotherapies, alone or associated with haematopoietic stem-cell transplantation, make the body's natural barriers extremely fragile. STIs can negatively impact both patient morbidity and mortality. In this Series paper, we discuss Chlamydia trachomatis, Neisseria gonorrhoeae, syphilis, human immunodeficiency virus, herpes simplex virus, human papilloma virus, and hepatitis B virus, as we found them to be associated with increased risks for haematological malignancy treatments, either by incidence or by severity. Protective measures and vaccines for patients with haematological malignancies are also discussed. Large, well conducted studies should be encouraged, with the aim to systematically analyse the impacts of STIs in patients with haematological malignancies, especially given the difficulties that antimicrobial resistance can confer to patient management.
Keywords: allogeneic stem cell transplantation, conditioning, graft versus host disease, infections, conditioning intensity
Background Multiple myeloma (MM) is a malignant disorder characterized by monoclonal differentiated plasma cells. While it is more commonly diagnosed in elderly individuals, it can also affect younger populations, though with a lower incidence. Case presentation Here, we present the case of a 32-year-old woman diagnosed with IgA lambda MM. She presented with fatigue, nausea, acute kidney injury (AKI) with a rapid increase in creatinine, and anemia. A kidney biopsy was done to rule out a rapidly progressive glomerular disease and a diagnosis was thus reached. A genetic workup revealed t(14;16) translocation and an extra copy of TP53. The patient received aggressive intravenous steroids and intravenous fluid resuscitation, resulting in an improvement in renal function. Treatment with daratumumab in combination with bortezomib, thalidomide, and dexamethasone was initiated and well tolerated. Despite the generally poor prognosis of IgA MM, our case emphasizes the importance of considering MM in young patients with unexplained kidney injury. Conclusion Early recognition and prompt intervention are essential in managing MM patients, especially in those with high-risk cytogenetic abnormalities. This case serves as a reminder for clinicians to maintain a high index of suspicion for MM, even in younger populations, when presented with unexplained kidney injury.
Context Donor-specific HLA antibodies (DSA) in haplo-SCT patients are associated with engraftment failure. Effective desensitization treatment is crucial for patients needing urgent transplants and lacking alternative donors. Objective To analyze outcomes of haplo-SCT in patients with DSA undergoing desensitization. Design A retrospective chart review of patients with hematologic malignancies who underwent haplo-SCT following desensitization therapy to reduce DSA burden from January 2017 to December 2023. Patient demographics, desensitization protocols, and post-transplant outcomes (ANC and platelet engraftment, GvHD, relapse, and overall survival) were analyzed. Setting The study was conducted at the American University of Beirut Medical Center. Interventions Patients received pretransplant desensitization with plasmapheresis, intravenous immunoglobulins, and rituximab. Results Sixteen patients were identified, median age 49 years, mainly female (68%); 75% had acute myeloid leukemia, and 25% had relapsed lymphoma. Active disease was present in 31% of patients at transplant time. 75% of donors were males, and donor-recipient sex mismatch was present in 56% of patients. Transplants were sourced from children (56%), siblings (19%), and parents (25%). Mean DSA levels before and after desensitization were 2935 and 685 mean fluorescence intensity (MFI), respectively, with mean differences of 2250 MFI. HLA antibodies against Class I, II, or both, were present in 56%, 44%, and 19% of patients, respectively. Bortezomib was added to the desensitization protocol in 37%. Median time between desensitization and transplant was 9 days. Twelve patients received myeloablative conditioning. GvHD prophylaxis for all included cyclosporine (day –3), post-transplant cyclophosphamide (days +3 and +5), and mycophenolate mofetil (day +6).The median time to ANC and platelet engraftment was 14 (12-39 days) and 24 (14-90 days), respectively. One patient had delayed ANC and 2 patients delayed platelet engraftment. Three patients died within 100 days of transplant (2 from infection, 1 from acute GVHD), and 13 patients remained in remission. The rates of acute and chronic GVHD were 37% and 12.5%, respectively. After a median follow-up of 16 months, the 1-year relapse-free survival and overall survival were 44%. Conclusion Haplo-SCT in patients with detectable DSA undergoing desensitization therapy demonstrated promising engraftment rates and acceptable long-term outcomes, bringing valuable insights into refining treatment protocols and patient outcomes.