Radwan Massoud

Efficacy and feasibility of sorafenib as a maintenance agent after allogeneic hematopoietic stem cell transplantation for Fms-like tyrosine kinase 3-mutated acute myeloid leukemia

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.

Nivolumab salvage therapy before or after allogeneic stem cell transplantation in Hodgkin lymphoma

Nivolumab salvage therapy before or after allogeneic stem cell transplantation in Hodgkin lymphoma

Hyper-CVAD Compared With BFM-like Chemotherapy for the Treatment of Adult Acute Lymphoblastic Leukemia. A Retrospective Single-Center Analysis

Background Several induction regimens have been developed for treatment of adult patients with acute lymphoblastic leukemia (ALL). However, only a few prospective randomized trials have directly compared these regimens. Patients and Methods In this report, we retrospectively evaluated the outcome of 62 adult ALL patients treated with either hyper‐CVAD (hyper fractionated cyclophosphamide, vincristine, doxorubicin, and dexamethasone; n = 38) or a BFM (Berlin–Frankfurt–Munster)‐like regimen (n = 24) between November 2000 and January 2016 at the American university of Beirut Medical Center in Lebanon. The feasibility of allogeneic stem cell transplantation (allo‐SCT) for those patients was also evaluated. Results The median follow‐up time was 29 (range, 1‐129) months. Fifteen (39%) and 10 (42%) patients underwent allo‐SCT in the hyper‐CVAD and BFM‐like group, respectively. At the time of the last follow‐up, 28 patients (74%) were in complete remission in the hyper‐CVAD group versus 18 patients (75%) in the BFM‐like group. Of those, 20 patients (53%) versus 11 patients (46%) were minimal residual disease‐negative at the last follow‐up, respectively. The 3‐year overall survival rate (71.9% vs. 76.9%; P = .808) and 3‐year disease‐free survival (54.7% vs. 76.4%; P = .435) were similar in hyper‐CVAD group compared with the BFM‐like group, respectively. Both chemotherapies were relatively well tolerated. Conclusion Overall, despite the older age and a greater number of patients with high‐risk category (including Philadelphia chromosome‐positive) in the hyper‐CVAD group, this did not translate into a difference in survival outcome between the 2 groups. The hyper‐CVAD regimen appears to be feasible for adult patients with ALL in terms of tolerability and efficacy. Micro‐Abstract Several induction regimens have been developed for adult patients with acute lymphoblastic leukemia (ALL). We show that the hyper‐CVAD (hyper fractionated cyclophosphamide, vincristine, doxorubicin, and dexamethasone) regimen appears to be feasible for adult patients with ALL in terms of tolerability and efficacy. The combination of tyrosine kinase inhibitors for Philadelphia chromosome‐positive (+) patients and rituximab for CD20+ patients were significantly more frequent in the hyper‐CVAD arm and might have affected outcomes favorably. There is still a need for large, prospective, randomized studies to establish the best induction regimen for adult ALL patients.

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

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

Thiotepa 10 mg/kg Treatment Regimen Is Superior to Thiotepa 5 mg/kg in TBF Conditioning in Patients Undergoing Allogeneic Stem-Cell Transplantation

Micro‐Abstract A study evaluating the optimal dose of myeloablation in thiotepa, busulfan, and fludarabine (TBF) conditioning included 29 patients who received TBF conditioning before allogeneic stem‐cell transplantation. Thirteen patients received 5 mg/kg thiotepa; the remaining 16 patients received 10 mg/kg. Patients deemed fit to receive 10 mg/kg conditioning had better overall and progression‐free survival than those who received 5 mg/kg, with no additional toxicities. 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.

Real Life Experience with Plerixafor and Granulocyte Colony-Stimulating Factor for Mobilization of Autologous Peripheral Stem Cell Transplantation

After a median follow up of 36 months, the 1-year TRM was 11% in the FB4 group, and 14% in the FB<4 group (p 1⁄40.7). The incidence of aGVHD grade II-IV was 22% in FB4 vs 14% in FB<4 (p 1⁄40.8), the incidence of cGVHD was 19%, with no significant difference between the two groups. We did not observe any significant difference at one year PFS (FB4: 87% vs FB<4: 67%) and OS (FB4: 84% vs FB<4: 87%). Conclusion: This riskadapted combined approach of selecting conditioning intensity minimizes post-transplant complications, without affecting survival. These findings need to be confirmed in larger studies.

Feasibility of Venetoclax-based combinations for adult patients with acute myeloid leukemia relapsing after allogenic stem cell transplantation

To the editor, Acute myeloid leukemia relapsing after allogeneic-stemcell-transplant (allo-SCT) (R/R-AML) is associated with poor prognosis and low cure rates [1, 2], despite variable therapeutic options including hypomethylating agents, chemotherapy (standard intensive induction/salvage therapies with anthracycline-cytarabine combinations, high dose cytarabine, fludarabine and cladribine-based combinations among others), donor lymphocyte infusion (DLI), and/or a second allo-SCT [3]. The B-cell leukemia/lymphoma2 (BCL-2) family proteins are anti-apoptotic molecules overexpressed in AML cells and associated with worse prognosis [4]. Venetoclax, a selective BCL-2 inhibitor, has been shown to be efficacious as monotherapy and in combination with hypomethylating agents for treatment of relapsed/refractory-AML, among other hematologic malignancies [5, 6]. However, limited data is available on the utility of venetoclax-based combinations post-SCT. We herein present four cases of R/R-AML treated with a combination of venetoclax with a hypomethylating agent and/or a targeted therapy.

Bendamustine as a bridge to allogeneic transplant in relapsed/refractory Hodgkin lymphoma patients who failed salvage brentuximab vedotin postautologous peripheral blood stem cell transplantation

Jean El Cheikh, Radwan Massoud, Basel Haffar, Elie Fares, Rami Mahfouz, Tamima Jisr, Mohamed A. Kharfan-Dabaja, Anas Mougharbel, Ali Youssef, Ali Bazarbachi and Ahmad Ibrahim Division of Hematology and Oncology, Department of Internal Medicine, American University of Beirut Medical Center, Beirut, Lebanon; Division of Hematology and Oncology, Makassed University hospital, Beirut, Lebanon; Department of Blood and Marrow Transplantation, H. Lee Moffitt Cancer Center, Tampa, FL, USA

Cytomegalovirus reactivation in lymphoma and myeloma patients undergoing autologous peripheral blood stem cell transplantation

BACKGROUND Cytomegalovirus reactivation is often diagnosed in allogeneic hematopoietic cell transplant recipients and therefore could lead to CMV-related disease, involving many organs in these immunocompromised patients. In contrast, few studies investigated CMV reactivation and end-organ disease in patients undergoing Autologous Peripheral Blood Stem Cell Transplant (ASCT) since they are considered at low risk for both reactivation and disease. OBJECTIVES The primary outcome of the analysis was to understand the difference in incidence of CMV reactivation between MM and Lymphoma patients. Secondary outcomes included the difference between MM and Lymphoma patients when considering the effect of CMV reactivation on transplant related mortality (TRM) overall survival (OS) progression free survival (PFS), risk factors for reactivation, and median time to reactivation. STUDY DESIGN In this report, we retrospectively compared the incidence, risk factors, and outcome of CMV reactivation in adult patients with Myeloma (MM) and Lymphoma undergoing ASCT at the American university of Beirut Medical Center in Lebanon (AUBMC). A total of 324 consecutive ASCT were performed between January 2005 and March 2016. Serial weekly monitoring for CMV quantification was done using a quantitative PCR, starting from transplantation until the hospital discharge and afterwards based on the clinical symptoms in cases of clinical suspicion of reactivation after discharge from the hospital. RESULTS The cumulative incidence of CMV reactivation was 16% (n=53) with a median time of 16 (range, 4-242) days after ASCT. The incidence of reactivation was significantly higher in the MM (22%) and NHL (20%) groups, when compared to the HL (4%) (P=0.001). There was a higher incidence of CMV reactivation according to age (≥50 vs ≤50 years) with higher incidence in the older population 24% vs 10% respectively (p=0.0043). The mean time to CMV reactivation was significantly higher in the NHL group with a mean of 53.7days when compared to the HL and MM groups with mean 19.75days and 12.66 (range, 4-34) days respectively (P=0.003). Twenty-two patients (76%) and three patients (75%) patients required specific antiviral therapy in the MM group and HL groups respectively; which was significantly higher (P<0.001) then the NHL group with 13 (65%) patients requiring specific antiviral therapy. Five patients (1.5%) developed CMV disease at a median of 60days (range, 7-107) post ASCT: there was significant difference in the mean-time to reactivation based on disease type MM versus lymphoma 10 versus 33days (P=0.007). In multivariate analysis, a higher age was associated with an increased risk of CMV reactivation; MM and NHL had higher risk of CMV reactivation when compared to HL, and progressive disease at transplant was associated with increased risk of CMV reactivation. After a median follow-up of 21.5 months (range: 1-125), there was no significant impact on PFS, however there was significant decrease in OS of lymphoma patients who had CMV reactivation when compared to those without CMV reactivation (204 and 112days respectively P=0.045). TRM increased from 1.1% in patients with no CMV reactivation to 13% in patients with CMV reactivation (P=0.003). CONCLUSION Our data suggests that CMV reactivation is not uncommon in ASCT recipients and may contribute to increase TRM. MM patients may have a higher incidence, of CMV reactivation with more anti-viral treatment requirements when compared to lymphoma patients, especially in older population.

Trends in hematopoietic stem cell transplant activity in Lebanon

Hematopoietic stem cell transplantation (HSCT) has been accessible to the population residing in Lebanon and surrounding countries since 1997. HSCT programs were developed in two major hospitals in Beirut: American University of Beirut Medical Center (AUBMC) and Makassed General Hospital. Mount Lebanon Hospital initiated an autologous HSCT activity later. Between 2012 and 2016, the HSCT activity in Lebanon reached a total of 897 transplants, among which 303 (33.8%) were allogeneic HSCT and 594 (66.2%) were autologous HSCT. Overall, autologous HSCT activity has remained stable over the past 5years, whereas allogeneic HSCT activity has seen a steep increase between 2012 and 2013 followed by a modest increase later. Haploidentical transplantation has mushroomed and represented almost half of allogeneic HSCT activity in 2016. AUBMC and Makassed General Hospital are members of the European Blood and Marrow Transplantation (EBMT) and East Mediterranean Blood and Marrow Transplantation groups, and AUBMC has been accredited by JACIE (Joint Accreditation Committee - ISCT & EBMT) since 2016. The past 5years have seen an increase in HSCT-related research and publications, mainly from AUBMC. These research activities were predominantly focused on personalized conditioning for allogeneic HSCT and post-transplant maintenance therapy.