Early T-Cell Precursor Leukemia: A High-Risk Subtype of Acute Lymphoblastic Leukemia, Single Center Experience in Jordan.

BACKGROUND AND OBJECTIVES: Early T-cell precursor (ETP) acute lymphoblastic leukemia/lymphoma (ALL/LBL) is a newly recognized entity of T-lymphoblastic leukemia/lymphoma. The optimal therapeutic approaches to adult patients are poorly studied. PATIENTS AND METHODS: We compared the outcomes of adult's patents with ETP-ALL/LBL who received frontline chemotherapy regimens with other T-ALL/LBL immunophenotypic subtypes. Patients with ETP-ALL/LBL were identified based on CD1a (-), CD8 (-), CD5 (-) (dim), and positivity for 1 or more stem cell or myeloid antigens. RESULTS: Sixty-nine patients were included between the years 2010 and 2021 (19 ETP-T-ALL/LBL; 50 non ETP- T-cell ALL/LBL). The median age was 26 year (IQR: 21, 33). Fifty-six patients presented as ALL, while 16 with lymphoblastic lymphoma. Forty-seven patients achieved complete remission, and 43 were alive at last encounter. The complete remission rate in patients with ETP-ALL/LBL was lower than that of non-ETP-ALL/LBL patients (32% vs. 68%; P = .2), and the MRD at end of induction was significantly higher (26% vs. 6.2%, P < .001), and more likely to receive allo-SCT consolidation in CR1 (95% vs. 40%, P < .001). After a median follow-up of survivors of 48 months (range: 32-74 months), the median overall survival for patients with ETP-ALL/LBL was not reached versus 11.5 months for the non-ETP-ALL/LBL patients (P = .014)). Twenty-six patients receive allo-SCT in CR1. There was no significant difference in overall survival (79% vs. 70%; P = .49) between both transplant-cohorts in both groups. CONCLUSION: ETP-ALL/LBL represents a high-risk disease subtype of adult ALL. Novel treatment strategies are needed to improve treatment outcomes in this patient's population.

The Impact of Graft CD3+ T-Cell Dose on the Outcome of T-Cell Replete Human Leukocyte Antigen-Mismatched Allogeneic Hematopoietic Peripheral Blood Stem Cells Transplantation.

Background: Data on whether the graft CD3-positive (CD3+) T-cell dose in T-cell-replete human leukocyte antigen (HLA)-mismatched allogeneic hematopoietic peripheral blood stem cells transplantation (PBSCT) influences post-transplant outcomes are controversial. Methods: Using King Hussein Cancer Center (KHCC) Blood and Marrow Transplantation (BMT) Registry database, 52 adult subjects, receiving the first T-cell-replete HLA-mismatched allogeneic hematopoietic PBSCT for acute leukemias or myelodysplastic syndrome, were identified, from January 2017 to December 2020. The cutoff value of graft CD3+ T-cell dose was identified using the receiver operating characteristic (ROC) formula and Youden's analysis. Subjects were divided into two cohorts: cohort 1 with low CD3+ T-cell dose (n = 34) and cohort 2 with high CD3+ T-cell dose (n = 18). Correlative analyses were performed between CD3+ T-cell dose and the risk of graft-versus-host disease (GvHD), relapse, relapse-free survival (RFS), and overall survival (OS). P-values were two-sided and considered significant when P < 0.05. Results: Subject covariates were displayed. Subject's characteristics were comparable, except for higher nucleated cells and more female donors in the high CD3+ T-cell cohort. The 100-day cumulative incidence of acute GvHD (aGvHD) was 45±7% and 3-year cumulative incidence of chronic GvHD (cGvHD) was 28±6.7%. There was no statistically significant difference between the two cohorts in aGvHD (50% vs. 39%, P = 0.4) or cGvHD (29% vs. 22%, P = 0.7). The 2-year cumulative incidence of relapse (CIR) was 67.5±16.3% for low compared with 14.3±6.8% for high CD3+ T-cell cohort (P = 0.018). Fifteen subjects relapsed and 24 have died, 13 due to disease relapse. There was an improvement in 2-year RFS (94% vs. 83%; P = 0.0022) and 2-year OS (91% vs. 89%; P = 0.025) in low CD3+ T-cell cohort compared with high CD3+ T-cell cohort. Graft CD3+ T-cell dose is the only significant risk factor for relapse (P = 002), and OS (P = 0.030) in univariate analysis which was maintained in multivariate for relapse (P = 0.003), but not for OS (P = 0.050). Conclusions: Our data suggest that high graft CD3+ T-cell dose is associated with lower risk of relapse, and might improve long-term survival, but has no influence on the risk of developing aGvHD or cGvHD.

Outcome of Primary Mediastinal Large B Cell Lymphoma Treated with RCHOP.

Purpose: Primary mediastinal large B-cell Lymphoma (PMLBCL) is a rare aggressive lymphoma with unique clinical, pathological, and molecular features. The optimal frontline therapy is subject of ongoing debate. Our study aims to evaluate the outcomes of PMLBCL treated with rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone (RCHOP) at King Hussein Cancer Center. Patients and Methods: Adult patients >18 years of age with PMLBCL treated with RCHOP from January 2011 to July 2020 were identified. All demographics, disease and treatment related variables were retrospectively collected. Correlations of clinical and laboratory variables with progression-free survival (PFS) and overall survival (OS) were determined by univariate and multivariate analyses using backward stepwise Cox regression models. The PFS and OS were plotted using Kaplan‒Meier curves. Results: 49 patients were included with a median age of 29 years. 14 (28.6%) had stage III or IV, 31 (63.3%) had mediastinal bulky disease. International prognostic index (IPI) was 0-1 in 35 (71.4%). Radiotherapy was given to 32 (65.3%) patients. End of treatment (EOT) response was complete (CR) in 32 (65.3%), partial response (PR) in 8 (16.3%) and progressive disease (PD) in 9 (18.4%). Patients who achieved CR at EOT, compared favorably with those who did not in regard to 4-year OS (92.5% vs 26.9%, p=<0.001). Overall objective response to salvage chemotherapies was 26.7%. At a median follow-up of 46 months, 4-year PFS and OS were 60% and 71% respectively. In multivariate analysis, IPI > one correlated with the EOT response (p=0.009), PFS (p=0.004) and OS (p= 0.019). Conclusion: In PMLBCL, RCHOP chemotherapy backbone in the frontline therapy is suboptimal but can be used in patients with low IPI. Adapting more intensive chemoimmunotherapy regimens may be considered for patients with high IPI. Salvage chemotherapy has limited activity in patients with relapsed or refractory disease.

Extramedullary acute myeloid leukemia (eAML): Retrospective single center cohort study on clinico-pathological, molecular analysis and survival outcomes.

INTRODUCTION: extramedullary acute myeloid leukemia (eAML) is characterized by extramedullary tumor formation infiltrated by myeloid blasts, with or without maturation and effaced architecture. The clinical, genetic and molecular aspects and overall outcomes are well defined worldwide, but not well characterized in our region. PURPOSE AND METHODS: This is a retrospective single center cohort study on 32 patients, who were identified over 10 years to study the clinical, pathologic and genetic-molecular aspects, and survival outcomes. RESULTS: eAML is rare (1%), occurs at a younger age with male predominance. Central nervous system (CNS) with facial bone invasion is most commonly identified (34.4%). 45.5% were positive for conventional myeloid markers (MPO), CD33, CD117, and 36% positive for CD34 and CD68. 54% with normal karyotype had deleterious mutations on further testing. NGS revealed pathogenic mutations in 76%(N-9/17) and none tested positive for P53, IDH1 or IDH2. At a median follow up time of 43mo (range, 8.6-80mo); 37.5%(N-12) were in complete remission, 62.5%(N-20) relapsed. 28% of relapses were after allotransplant. 31%(N-10) alive and continued in complete remission(CR), and 69%(N-22) of patients have died.Median overall survival (OS) is 18.4 and relapse free survival (RFS) 18.7 months. OS and RFS were significantly better in patients, who attained CR after induction (IC 11.9 mo vs zero; P = 0.0001; IC 12mo vs zero; P = 0.0001) compared to patients with relapsed disease; and in patients who received allo-transplant consolidation with median OS and RFS 42 vs 8.5mo (P = 0.002) and 42months vs 10 mo (P = 0.006). Thus allotransplant may be considered for all eligible patients in first CR. CONCLUSION: achievement of complete remission after induction therapy is associated with improved outcomes in eAML. Allotransplant in first complete remission may be the most effective modality for achieving long-term remissions.