Hematopoietic stem cell transplantation (HSCT) is now an established treatment modality with definitive indications for many hematological disorders. However, this line of treatment requires tremendous resources, and it becomes increasingly difficult for transplanters practicing in the developing world to reconcile the difference between what is possible and what is available. On the basis of 30 years of experience and more than 4250 transplants , this article will focus on the challenges faced our HSCT program and how they were solved. The HSCT program in Egypt started in 1989 on a narrow scale and since that time we faced many challenges.In 1997, the transplant rate increased dramatically with the opening of many HSCT units distributed allover Egypt. Our team is registered in the Center for International Blood and Marrow Transplant Research ,and the number of transplants performed till December 2019 exceeded 4000 cases (60% allogeneic and 40% autologous).
BACKGROUND: Philadelphia chromosome-like acute lymphoblastic leukemia (Ph'-like ALL) is characterized by a gene-expression profile similar to that of BCR-ABL1 positive ALL and a poor outcome. Rearrangements of cytokine receptor like factor 2 (CRLF2) are identified in approximately 50% of Ph'-like and 10% of B-other ALL patients.
AIM: To identify the incidence of CRLF2 rearrangements and the frequency of relapse in a cohort of B-other Precursor B-ALL adults Egyptian patients who were treated with conventional therapy at National Cancer Institute, Cairo University.
METHODS: The routine diagnostic work-up at diagnosis included Bone marrow aspiration, immunophenotyping, karyotyping, fluorescent in situ hybridization (FISH) for BCR-ABL1 and KMT2A (MLL) and CRLF2 rearrangements (IGH-CRLF2 or P2RY8-CRLF2), and molecular analyses of BCR-ABL1 translocations. Patients within the age group 18-25 years received Total XV protocol while patients >25 years received Hoelzer's protocol.
RESULTS: Forty patients were included (22 males, 18 females). Median age at diagnosis was 25 years (18 -65). Median TLC was 14.9 x109/L (1.1 - 201), median Hb was 9.9 gm/dl (5-12.9), median platelet count was 47 x 109/L (19-359) and median BM blasts count was 90% (30-100). CRLF2 rearrangement was detected in 4/40 (10%) patients. All CRLF2 positive patients (100%) relapsed at 6 months vs. 11/36 (30%) CRLF2 negative (p<0.001). At 6 months follow up, disease free survival (DFS) was 70% in CRLF2 negative patients vs. 0% in CRLF2 rearranged (p=0.04). At 1 year follow up, overall survival (OS) was 30 (75%) for CRLF2 negative vs. 0 (0%) for CRLF2 positive patients (p=0.01).
CONCLUSION: CRLF2 rearrangements constitute a high risk independent prognostic factor in adult precursor B-ALL patients denoting a poor outcome and should be studied in ALL Ph' negative patients. Additional TKI therapy should be included for this category of patients in our protocols to improve outcome.
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Disclosures
No relevant conflicts of interest to declare.
Consistent with adult studies, in children and adolescents with obesity, non-HDL cholesterol may play a role in the etiology of psychosocial dysfunction. Further studies are warranted.
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