الفهرس 
Acute Lymphoblastic Leukemia in AdultsOnly 14 pages are availabe for public view
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Abstract
A
cute lymphoblastic leukemia (ALL) is a malignant transformation and proliferation of lymphoid progenitor cells in the bone marrow, blood and extra-medullary sites. The incidence of ALL follows a bimodal distribution, with the first peak occurring in childhood and a second peak occurring around the age of 50.
Acute lymphoblastic leukemia (ALL) is the second most common acute leukemia in adults, with an incidence of over 6500 cases per year in the United States alone. The hallmark of ALL is chromosomal abnormalities and genetic alterations involved in differentiation and proliferation of lymphoid precursor cells.
Allogeneic hematopoietic stem cell transplantation (HSCT) with a myeloablative conditioning regimen is considered the most potent post-remission anti-leukemic therapy in adult acute lymphoblastic leukemia (ALL).
Total body irradiation (TBI)-based conditioning regimens are considered standard for patients undergoing allergenic hematopoietic cell transplantation (HCT) for acute lymphoblastic leukemia (ALL), with expected survival rates of 50% to 60% in first complete remission (CR1).
However, TBI-based regimens are associated with serious lifelongbadverse events (AEs), including interstitial pneumonia, cataracts, endocrine disturbances, and secondary malignancies.
Over the past few decades, intravenous busulfan (Bu) is introduced as the conditioning for allo-HSCT. Although busulfan-containing regimens can produce comparable outcomes with lower TRM, the oral form has wide variability in the absorption and metabolism. Also, high relapse rates have been observed with low levels of busulfan, while many risks including veno-occlusive disease (VOD) have been related to higher levels. Many studies have been carried out to evaluate the effect of different regimens on transplant outcomes, but the ideal conditioning regimen for adult ALL patients remains unknown.
Our retrospective study conducted on 84 adult Egyptian patients with ALL, who were candidates for allogenic hematopoitic stem cell transplantation between 2005-2014 at the BMT Unit at Nasser Institute Hospital for Research& Treatment, Ministry of Health& Population. We Compared between TBI/CY versus BU/CY as a conditioning regimens before Allogenic Hematopoetic stem cell transplantation, as regard; transplant outcomes (DFS& OS) & regimen related toxicities& TRM. It was TBI/CY group (n=62) and BU/CY group (n=22), with the same inclusion and exclusion criteria.
TBI/CY appears to be superior to BU/CY as a conditioning regimen for adult patients with ALL who are candidates to allogenic HSCT, as regard survival rates, OS& shows higher DFS with lower relapse rates. However, the regimen related toxicity (hemorrhagic cystitis) remains the challenge.
Conclusion & Recommendation
TBI/CY appears to be superior to BU/CY as a conditioning regimen for adult patients with ALL who are candidates to allogenic HSCT, as regard survival rates, OS& shows higher DFS with lower relapse rates. However, the regimen of TBI/CY related toxicity like, hemorrhagic cystitis, long hospital stay& TRM, remains the challenge.
Our study included 24 patients who were high risk & Ph+. Out of them, 20 received TBI/CY and only 4 who received BU/CY regimen. So, we couldn’t have enough number of patients in each group to compare.
Our recommendations:
1. Conduct more studies that include larger number of patients in BU/CY group to obtain statistical results that compares outcome between subtypes of acute lymphoblastic leukemia.
2. Conduct more retrospective studies, including larger number of Ph+ ALL in TBI/CY versus BU/CY, to study which regimen is more effective in high risk ALL in adults, as regard DFS& OS.
3. Careful monitoring of early and late complications to study regimen related toxicity, as well as prospective randomized trials, hopefully will establish optimal conditioning regimens in allogenic hematopoietic stem cell transplant for acute lymphoblastic leukemia in adults.