Clinical Characteristics and Outcomes of CML in Adolescents and Young Adults.

BACKGROUND: While Chronic Myeloid Leukemia (CML) is a disease of older adults, there is a growing population of adolescent and young adults (AYAs) with CML. This study evaluated the clinical characteristics and outcomes of CML in AYAs. PATIENTS AND METHODS: Data from medical records of adults with chronic phase CML diagnosed and treated at our center from 2011until 2021were retrospectively analyzed. Age between 18 and 29 years was used to define AYAs. Response to tyrosine kinase inhibitors (TKIs), progression to accelerated phase (AP) or blast crisis (BC), event-free survival (EFS) and overall survival (OS) were compared between AYAs and older adults. RESULTS: Among 163 patients included, 41 (25.1%) were AYAs. AYAs were more likely to be males (P = .02), to present with symptoms (P = .004), had a higher median white blood cell count (P = .007), neutrophil count (P = .029), eosinophil count (P = 0.01), low-risk Sokal (P = .033) and Hasford (P = .005) groups. TKI-sensitivity as well as median times for achievement of complete cytogenetic and major molecular response were comparable between both groups. After a median follow-up of 76 (range: 11-235) months, there was no difference in OS (P = .528), or cumulative incidence of transformation to accelerated phase or blast crisis (P = .11). On the other hand, AYA had an inferior EFS (P = .034). CONCLUSION: A quarter of the patients diagnosed with CML in our population were AYAs. Despite being characterized as "lower-risk," they presented with a greater disease burden, had a shorter EFS but comparable OS. Further studies are needed to better understand the disease biology of this group.

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.

Influence of FLT3-ITD and NPM1 status on allogeneic hematopoietic cell transplant outcomes in patients with cytogenetically normal AML.

OBJECTIVE: In individuals with cytogenetically normal (CN) AML, disease risk is estimated using molecular features such as the status of NPM1 and FLT3-ITD genes. However, data regarding the impact of NPM1 and FLT3-ITD status on hematopoietic stem cell transplant (HCT) outcomes are limited. We examined the effect of NPM1 and FLT3-ITD status on transplant outcomes in 131 CN AML patients transplanted at Princess Margaret Hospital between 2006 and 2017. METHODS: Overall survival (OS) was calculated using Kaplan-Meier analysis and multivariable Cox proportional hazards regression. Cumulative incidence of relapse (CIR) and non-relapse mortality (NRM) were calculated using competing risk regression. RESULTS: There was no difference in 3-year OS among NPM1+ /FLT3-ITD- , NPM1- /FLT3-ITD- , NPM1+ /FLT3-ITD+ and NPM1- /FLT3-ITD+ patients: 56% (95% CI, 29%-76%), 61% (95% CI, 46%-73%), 53% (95% CI, 34%-70%) and 52% (95% CI, 17%-78%), respectively. CIR at 3-years was similar among NPM1- /FLT3-ITD- , NPM1+ /FLT3-ITD+ and NPM1- /FLT3-ITD+ patients-14% (95% CI, 6%-26%), 13% (95% CI, 4%-28%) and 19% (95% CI, 4%-41%), respectively-while there were no relapses in the NPM1+ /FLT3-ITD- group. NRM at 3 years for NPM1+ /FLT3-ITD- , NPM1- /FLT3-ITD- , NPM1+ /FLT3-ITD+ and NPM1- /FLT3-ITD+ patients was similar at 44% (95% CI, 19%-67%), 38% (95% CI, 25%-50%), 43% (95% CI, 25%-59%) and 44% (95% CI, 14%-71%), respectively. CONCLUSION: NPM1 and FLT3-ITD status may provide limited prognostic information about transplant outcomes in CN AML patients.

Physical therapy pathway and protocol for patients undergoing hematopoietic stem cell transplantation: Recommendations from The Eastern Mediterranean Blood and Marrow Transplantation (EMBMT) Group.

BACKGROUND: Patients undergoing hematopoietic stem cell transplantation (HSCT) are often referred for physical therapy (PT) to help improve their quality of life. However, to our knowledge there is no clear PT pathway to guide therapists and patients before, during, and after HSCT. METHODS: A comprehensive literature review was carried out exploring the role and benefits of PT in HSCT patients. The current evidence was comlimented with recommendations and opinions from the experts in the field, which included PT's and hematology consultants from PTAGVHD and the EMBMT group. RESULT: A clear pathway and protocol as a working guide for rehabilitation professionals working with the HSCT patient's was developed. CONCLUSION: This paper not only reviews the current evidence on safe PT practice but also puts forward a protocol and pathway for HSCT rehabilitation, highlights the importance of individualized exercise intervention for HSCT patients, and outlines safe practice guidelines for the physical therapists working in this field.