tretinoin and Abnormal-Karyotype

Individuals who are exposed to cytotoxic agents are at risk of developing therapyrelated myeloid neoplasms (t-MN). Cytogenetic findings of a neoplasm play an important role in stratifying patients into different risk groups and thus predict the response to treatment and overall survival.. A 59-year-old man was diagnosed with acute promyelocytic leukaemia. Following this, he underwent all-trans retinoic acid (ATRA) based chemotherapy and achieved remission. Four years later, the disease relapsed and he was given idarubicin, mitoxantrone and ATRA followed by maintenance chemotherapy (ATRA, mercaptopurine and methotrexate). He achieved a second remission for the next 11 years. During a follow-up later, his full blood picture showed leucocytosis, anaemia and leucoerythroblastic picture. Bone marrow examination showed hypercellular marrow with trilineage dysplasia, 3% blasts but no abnormal promyelocyte. Fluorescence in-situ hybridisation (FISH) study of the PML/RARA gene was negative. Karyotyping result revealed complex abnormalities and monosomal karyotype (MK). A diagnosis of therapy-related myelodysplastic syndrome/myeloproliferative neoplasm with unfavourable karyotypes and MK was made. The disease progressed rapidly and transformed into therapy-related acute myeloid leukaemia in less than four months, complicated with severe pneumonia. Despite aggressive treatment with antibiotics and chemotherapy, the patient succumbed to the illness two weeks after the diagnosis.. Diagnosis of t-MN should be suspected in patients with a history of receiving cytotoxic agents. Karyotyping analysis is crucial for risk stratification as MK in addition to complex aberrant karyotypes predicts unfavourable outcome. Further studies are required to address the optimal management for patients with t-MN.

Topics: Abnormal Karyotype; Antineoplastic Combined Chemotherapy Protocols; Humans; Idarubicin; In Situ Hybridization, Fluorescence; Karyotyping; Leukemia, Myeloid, Acute; Leukemia, Promyelocytic, Acute; Male; Mercaptopurine; Methotrexate; Middle Aged; Mitoxantrone; Neoplasm Recurrence, Local; Neoplasms, Second Primary; Tretinoin

The translocation t(15;17), which results in the PML-RARα fusion gene, is a characteristic chromosomal translocation in acute promyelocytic leukemia (APL). But additional chromosome aberrations in APL are increasingly recognized. Here, we report on a 16-year-old APL patient who had an fms-related tyrosine kinase 3-internal tandem duplication (FLT3-ITD) and a 46,XY,t(15;17)(q22;q21)-16+mar karyotype at diagnosis. The patient achieved complete remission after induction therapy with all-trans retinoic acid and chemotherapy. But he soon relapsed presenting distinctive APL features in the bone marrow and leptomeninges and showing a chromosome translocation change involving chromosomes 7 and 16 besides t(15;17)(q22;q21). The new karyotype 46,XY,t(7;16)(q31;q22),t(15;17)(q22;q21) was determined. To the best of our knowledge, this is the first report of a de novo APL with a chromosome translocation t(7;16)(q31,q22) together with a t(15;17)(q22;q21) and FLT3-ITD mutation.

Topics: Abnormal Karyotype; Adolescent; Brain; Chromosomes, Human, Pair 15; Chromosomes, Human, Pair 16; Chromosomes, Human, Pair 17; Chromosomes, Human, Pair 7; fms-Like Tyrosine Kinase 3; Humans; Leukemia, Promyelocytic, Acute; Male; Mutation; Radiography; Recurrence; Translocation, Genetic; Tretinoin

This retrospective study performed by the Eastern Cooperative Oncology Group and the Southwest Oncology Group enrolled 140 acute promyelocytic leukemia (APL) patients with t(15;17) to determine the influence of additional karyotypic abnormalities on treatment outcome. Karyotypes were centrally reviewed by both study groups. The complete response rate after induction for patients with t(15;17) treated with chemotherapy, or all-trans retinoic acid (ATRA) as induction therapy was not affected by additional cytogenetic aberrations. Disease-free (DFS) and overall survival (OS) were unaffected by additional cytogenetic abnormalities if treatment was chemotherapy without ATRA. Patients with t(15;17) only, treated with ATRA with or without chemotherapy, had an improved DFS (P = 0.06) and a better OS (P = 0.01) compared with ATRA-treated patients with additional cytogenetic abnormalities. Patients with APL and t(15;17) alone are significantly more sensitive to treatment with ATRA than are patients with t(15;17) and additional cytogenetic abnormalities.

Topics: Abnormal Karyotype; Adolescent; Adult; Aged; Antineoplastic Agents; Chromosome Aberrations; Chromosomes, Human, Pair 15; Chromosomes, Human, Pair 17; Disease-Free Survival; Drug Resistance, Neoplasm; Female; Humans; Leukemia, Promyelocytic, Acute; Male; Middle Aged; Prognosis; Retrospective Studies; Tretinoin; Young Adult