Clinical prevalence and outcome of cardiovascular events in the first 100 days postallogeneic hematopoietic stem cell transplant.

INTRODUCTION: Recent advances in allogeneic hematopoietic stem cell transplant (HSCT) have allowed us to offer HSCT to older, advanced disease patients with more co-morbidities. Cardiovascular toxicity post-transplant is a major concern due to the increased risk of mortality. Few studies have examined the prevalence of CV events including CAD (MI, angina, PCI, CABG, CHF, arrhythmias), HTN, stroke/TIA, and death in the first 100 days post-transplant. PATIENTS: We assessed the impact of pretransplant MUGA results in predicting postallogeneic HSCT CV events and overall survival in the first 100 days, and whether or not transient anthracycline-induced cardiomyopathy or cumulative anthracycline dose affected overall survival. This retrospective, cohort study included 665 patients with a median age of 52 years who underwent HSCT from 2009 to 2015. RESULTS: The most frequent CV event in the first 100 days post-HSCT was arrhythmia seen in 2.9% of patients followed up by CHF (12.3%), MI (9%), and angina (8%). Two patients had PCI, and both survived the first 100 days. Cardiovascular risk factors predict for a poor MUGA scan but not survival. Higher dose anthracycline pretransplant predicted for a poor outcome. CONCLUSION: A history of CV disease, MI, or CAD was the most important predictive of CV events, P-value = .00002. 88.6% survived the first 100 days. Patients with an EF < 50% had a significant likelihood of having a CV event compared to patients with an EF > 60% (OR = 5.3, 95% CI [1.6-18.1], P = .0219). Cumulative anthracycline dose did not have a significant impact on overall survival.

Comparison of a modified pediatric protocol versus a hyper-CVAD protocol in adolescents and young adults with Philadelphia-negative acute lymphoblastic leukemia: A multicenter retrospective analysis.

BACKGROUND: The outcomes of Pediatric acute lymphoblastic leukemia (ALL) have improved dramatically whereas outcomes for ALL amongst adolescents and young adults (AYA) have lagged behind. The introduction of pediatric-like regimens to manage adult ALL has shown promising outcomes across several analyses. MATERIALS AND METHODS: In this analysis, we aimed to retrospectively compare the differences in outcomes among patients aged 14-40 years with Philadelphia-negative ALL treated with a Hyper-CVAD protocol versus a modified pediatric protocol. RESULTS: A total of 103 patients were identified with 58 (56.3%) in the modified ABFM group and 45 (43.7%) in the hyper-CVAD group. The median duration of follow-up for the cohort was 39 months (range 1-93). There were significantly lower rates of MRD persistence after consolidation (10.3% vs. 26.7%, P = 0.031) and transplantation (15.5% vs. 46.6%, P < 0.001) in the modified ABFM group. 5-year OS rates (83.9% vs. 65.3%, P = 0.036) and DFS rates (67.4% vs. 44%, P = 0.014) were higher in the modified ABFM groups. The incidence of grade 3 and 4 hepatotoxicity (24.1% vs. 13.3%, P < 0.001) and osteonecrosis (20.6% vs. 2.2%, P = 0.005) were higher in the modified ABFM group. CONCLUSION: Our analysis demonstrates that the use of a pediatric modified ABFM protocol demonstrated superior outcomes compared to the hyper-CVAD regimen in the treatment of Philadelphia-negative ALL amongst AYA patients. However, the modified ABFM protocol was associated with an increased risk of certain toxicities including high grade liver toxicity and osteonecrosis.

Saudi Arabian CML patient with a novel four-way translocation at t(9;22;5;2)(q34;q11.2;p13;q44).

BACKGROUND: The vast majority of chronic myeloid leukemia (CML) patients have a single translocation t(9;22)(q34;q11), BCR/ABL1 fusion genes, which is regarded as the hallmark of CML. However, around 5 to 10% of CML patients exhibit the involvement of a third chromosome. In some very rare cases a fourth or even fifth chromosome can be involved with the t(9;22). METHODS: This case report is based on a 40-year-old Saudi Arabian male patient, diagnosed with CML in lymphoid blast crisis, and observed to have a four-way 46 XY, t(9;22;5;2)(q34;q11.2;p13;q44) translocation. The BCR/ABL1 fusion was identified by fluorescent in situ hybridization (FISH). Additionally, the BCR/ABL1 p210 mRNA fusion transcripts were identified by a molecular test. RESULTS: The clinical and prognostic impact of additional partner chromosomes to t(9;22) remains unknown. The CML patient with this novel four-way translocation t(9;22;5;2) progressed to blast crisis and was resistant to Tyrosine Kinase Inhibitor (TKI) therapy. Therefore, this case is more in alignment with the negative impact of additional partner chromosomes to the translocation at t(9;22). CONCLUSION: Here we report for the first time a novel four-way translocation at t(9;22;5;2)(q34;q11.2;p13;q44).

Outcome of CD20-positive Adult B-cell Acute Lymphoblastic Leukemia and the Impact of Rituximab Therapy.

BACKGROUND: In adult B cell precursor acute lymphoblastic leukemia (BCP-ALL), CD20 expression has generally been associated with an adverse prognosis. Incorporating rituximab to standard of care is found to improve the outcome of CD20+ BCP-ALL. The aim of this study is to estimate the prognostic effect of CD20 expression and the impact of rituximab in BCP-ALL in Saudi Arabia. PATIENTS AND METHODS: We performed a retrospective study of 55 Saudi adult patients with BCP-ALL in King Fahad Specialist Hospital in Dammam from 2008 to 2017. RESULTS: The proportion of CD20+ cases was approximately 55%. Excluding rituximab-treated patients, the 5-year overall survival (OS) rate of CD20+ patients was lower than CD20- patients (56% vs. 66%; P = .62). Among CD20+ patients, the proportion that received rituximab was approximately 27%. Comparing CD20+ patients with and without rituximab, all patients who received rituximab achieved complete remission (CR) 4 weeks post-induction. The 3-year OS rate (88% vs. 63%; P = .35) and the 2-year event-free survival rate (70% vs. 68%; P = .75) were in favor of rituximab. In univariate and multivariate analyses, CR 4 weeks post-induction is recognized as an independent predictor of outcome. However, differences in survival rates did not have a statistical significance. CONCLUSION: CD20 expression in adult patients with BCP-ALL seems to be higher in Saudi Arabians than in Caucasians, and it seems to have a tendency towards an inferior outcome in terms of OS. Incorporating rituximab to standard of care seems to improve the outcome in terms of CR, OS, and event-free survival.

Risk of Thrombosis in Adult Philadelphia-Positive ALL Treated with an Asparaginase-Free ALL Regimen.

BACKGROUND: venous thromboembolism (VTE) is a well-known complication in adults with acute lymphoblastic leukemia (ALL), especially in patients treated with asparaginase (ASNase)-including regiments. However, VTE risk in adult Philadelphia-positive ALL (Ph+ve ALL) patients treated with non-hyperCVAD chemotherapy is unclear. In this study, we examined VTE incidence in adult Ph+ve ALL patients treated with imatinib plus a pediatric-inspired asparaginase (ASNase)-free regimen modified from the Dana Farber Cancer Institute (DFCI) ALL protocol. METHODS: a single centre retrospective review of Ph+ve ALL patients treated at Princess Margaret Cancer Center (PMCC) from 2008-2019 with imatinib plus modified DFCI protocol was conducted. RESULTS: of the 123 patients included, 30 (24.3%) had at least 1 radiology confirmed VTE event from diagnosis to the end of maintenance therapy. 86.7% (26/30) of the VTE events occurred during active treatment. Of all VTE events, the majority (53.3%) were DVT and/or PE while another significant portion were catheter-related (40.0%). Major bleeding was observed in 1 patient on VTE treatment with low molecular weight heparin (LMWH). CONCLUSION: a high VTE incidence (24.3%) was observed in adults Ph+ve ALL patients treated with imatinib plus an ASNase-free modified DFCI pediatric ALL protocol, suggesting prophylactic anticoagulation should be considered for all adult Ph+ve ALL patients including those treated with ASNase-free regimens.

Hodgkin Lymphoma Outcome: A Retrospective Study from 3 Tertiary Centers in Saudi Arabia.

BACKGROUND: Hodgkin lymphoma (HL) exhibits considerable clinicopathological variations in different parts of the world. This study was prompted by the limited availability of HL data in developing countries (particularly long-term outcomes). METHODS: We performed a retrospective review of eligible adult HL patients treated at 3 tertiary centers in Saudi Arabia between January 1997 and December 2012. RESULTS: The review included 340 patients with a median age of 26 years (range 15-82 years); 53% were male, 74% had an advanced stage, 22% had bulky disease, and 70% had low-to-intermediate risk according to the International Prognostic Score. Nodular sclerosis was the most common histological subtype (59%). Adriamycin, bleomycin, vinblastine, and dacarbazine (ABVD) was offered to 92% and radiotherapy to 43%. Initial therapy outcomes were complete response, partial response, and progressive disease in 91%, 5%, and 2% of patients, respectively. At a median follow-up of 39 months, the actuarial freedom from treatment failure at 5 years was 74%, with a 5-year overall survival of 91%. Multivariate analysis showed that advanced disease stage and high-risk international prognostic index independently predicted an adverse outcome. CONCLUSION: Our Saudi patient population exhibited outcomes that were comparable to those reported in developed countries.