Ultrastructural Observations in Therapy-Related Panmyelosis

McKenna, Robert W.; Parkin, Janet L.; Brunning, Richard D.

doi:10.1007/978-1-4613-2823-0_8

Human Leukemias 1984

DOI: 10.1007/978-1-4613-2823-0_8

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Ultrastructural Observations in Therapy-Related Panmyelosis

Robert W. McKenna¹,

Janet L. Parkin²,

Richard D. Brunning³

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1988

1992

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Cited by 2 publications

References 51 publications

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Short remission durations in therapy-related leukemia despite cytogenetic complete responses to high-dose cytarabine

Larson

Wernli

Beau

et al. 1988

Blood

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Seventeen patients with therapy-related myelodysplastic syndrome (t- MDS) or therapy-related acute nonlymphocytic leukemia (t-ANLL) were treated with single-agent high-dose cytarabine (HDAC; 1 to 3 g/m2 every 12 hours for 12 doses). The initial neoplasm was still present in eight patients when t-MDS/t-ANLL developed. Fifteen of the 16 patients with chromosomal abnormalities in bone marrow cells had loss or rearrangement of chromosomes 5 and/or 7. One patient had a t(15;17), and one had inadequate material for cytogenetic analysis. Twelve patients had normal metaphase cells (3% to 71%). Indications for HDAC therapy were progressive pancytopenia in 13 patients or rising blast count in four. Five patients died of marrow hypoplasia following therapy. Four others had refractory t-ANLL and died within the subsequent 5 months. Only one of ten patients with a poor performance status (PS greater than or equal to 2 using the ECOG scale) achieved a complete remission, but all seven patients with a good performance status (PS less than or equal to 1) had a complete remission. Hematologic remissions were achieved in 8 patients (47%) after one (6 patients) or two (2 patients) induction courses and were confirmed by recovery of a 100% normal marrow karyotype in six of the seven patients who were retested. Patients in remission received one to four consolidation courses with HDAC alternating with cytarabine/doxorubicin, but seven relapsed within 8 months (median remission duration, 5 months). In every case, the original chromosomal abnormality reappeared at relapse. HDAC has a high response rate for good-performance patients with t-MDS/t-ANLL, but complete remissions are short even when confirmed cytogenetically and consolidated intensively.

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Short remission durations in therapy-related leukemia despite cytogenetic complete responses to high-dose cytarabine

Larson

Wernli

Beau

et al. 1988

Blood

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Chromosomal loss and deletion are the most common mechanisms for loss of heterozygosity from chromosomes 5 and 7 in malignant myeloid disorders

Neuman

Cheng

Rios

et al. 1992

Blood

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We have examined a population of patients with acute myeloid leukemia (AML) or myelodysplastic syndrome (MDS) for loss of heterozygosity of polymorphic markers on chromosomes 5 and 7. The rationale for this study was the observation that the majority of patients with therapy- related leukemia (t-AML or t-MDS), resulting from cytotoxic treatment for prior malignancies, have loss of chromosome 5 and/or 7 or deletions involving the long arms of one or both of these chromosomes. This cytogenetic finding suggested that tumor-suppressor genes, important in the development of AML, may be located in these chromosomal regions. We analyzed a total of 60 patients, 43 with primary MDS/AML de novo and 17 with t-MDS/t-AML. Leukemia cells were evaluated for restriction fragment length polymorphisms (RFLPs). Leukemia cell genotypes were compared with lymphoblastoid cell genotypes from the same patients. Two cases of loss of heterozygosity were identified from chromosomes lacking visible deletions: one involving chromosome 5 in a patient with AML de novo who had a visible deletion of 5q at a later stage of the disease, and one involving chromosome 7 in a patient with t-AML. We conclude that allele loss from loci on chromosomes 5 and 7 in MDS/AML, when it occurs, usually results from major deletion or simple chromosome loss, rather than from mitotic recombination or chromosome loss with duplication of the remaining homologue.

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Ultrastructural Observations in Therapy-Related Panmyelosis

Cited by 2 publications

References 51 publications

Short remission durations in therapy-related leukemia despite cytogenetic complete responses to high-dose cytarabine

Short remission durations in therapy-related leukemia despite cytogenetic complete responses to high-dose cytarabine

Chromosomal loss and deletion are the most common mechanisms for loss of heterozygosity from chromosomes 5 and 7 in malignant myeloid disorders

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