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Title: Therapy-related acute myeloid leukemia and myelodysplastic syndrome: a clinical and morphologic study of 65 cases

Abstract

This study consists of 65 patients (pts) who developed a myelodysplastic syndrome (MDS) (39 pts) or acute myeloid leukemia (AML) (26 pts) following chemotherapy and/or radiotherapy; the interval from the onset of therapy to bone marrow abnormality ranged from 11 to 192 months (median, 58). Thirty-three patients had been previously treated for lymphoproliferative diseases, 29 for carcinoma, and three for a nonneoplastic disorder. Approximately 30% of the cases presenting in the MDS phase evolved to AML in one to 12 months (median, 3.5). The AML in 49% of the cases was not readily classified according to French-American-British (FAB) criteria; the primary difficulty in classification related to the involvement of multiple cell lines. Among the cases that could be classified, all FAB types were represented except for M1; M2 was the most frequent type. Clonal chromosome abnormalities were found in marrow specimens from 22 of 24 (92%) patients studied with G banding; 11 had abnormalities of chromosomes 5 and/or 7. The median survival for all patients was four months with no significant difference between those treated and not treated with antileukemic therapy. The median survival was three months for the patients presenting with AML, six months for the patients with AMLmore » following an MDS, and four months for the patients with an MDS that did not evolve to AML. The findings in the present study suggest that there are three stages of therapy-related panmyelosis: (1) pancytopenia with associated myelodysplastic changes, (2) a frank MDS, and (3) overt AML. Many patients will present in the stage of overt AML that differs from de novo AML primarily by the high incidence of trilineage involvement, difficulty in classification, frequent cytogenetic abnormalities, and poor response to antileukemic therapy.« less

Authors:
; ; ;
Publication Date:
OSTI Identifier:
5021579
Resource Type:
Journal Article
Resource Relation:
Journal Name: Blood; (United States); Journal Volume: 6
Country of Publication:
United States
Language:
English
Subject:
62 RADIOLOGY AND NUCLEAR MEDICINE; MYELOID LEUKEMIA; CHEMOTHERAPY; RADIOTHERAPY; BONE MARROW; CELL PROLIFERATION; CHLORAMBUCIL; CHROMOSOMAL ABERRATIONS; PATIENTS; SURVIVAL TIME; AMINES; ANIMAL TISSUES; ANTINEOPLASTIC DRUGS; BODY; CARBOXYLIC ACIDS; DISEASES; DRUGS; HEMATOPOIETIC SYSTEM; HEMIC DISEASES; LEUKEMIA; MEDICINE; MONOCARBOXYLIC ACIDS; MUTATIONS; NEOPLASMS; NUCLEAR MEDICINE; ORGANIC ACIDS; ORGANIC CHLORINE COMPOUNDS; ORGANIC COMPOUNDS; ORGANIC HALOGEN COMPOUNDS; ORGANS; RADIOLOGY; THERAPY; TISSUES; 550602* - Medicine- External Radiation in Diagnostics- (1980-)

Citation Formats

Michels, S.D., McKenna, R.W., Arthur, D.C., and Brunning, R.D. Therapy-related acute myeloid leukemia and myelodysplastic syndrome: a clinical and morphologic study of 65 cases. United States: N. p., 1985. Web.
Michels, S.D., McKenna, R.W., Arthur, D.C., & Brunning, R.D. Therapy-related acute myeloid leukemia and myelodysplastic syndrome: a clinical and morphologic study of 65 cases. United States.
Michels, S.D., McKenna, R.W., Arthur, D.C., and Brunning, R.D. 1985. "Therapy-related acute myeloid leukemia and myelodysplastic syndrome: a clinical and morphologic study of 65 cases". United States. doi:.
@article{osti_5021579,
title = {Therapy-related acute myeloid leukemia and myelodysplastic syndrome: a clinical and morphologic study of 65 cases},
author = {Michels, S.D. and McKenna, R.W. and Arthur, D.C. and Brunning, R.D.},
abstractNote = {This study consists of 65 patients (pts) who developed a myelodysplastic syndrome (MDS) (39 pts) or acute myeloid leukemia (AML) (26 pts) following chemotherapy and/or radiotherapy; the interval from the onset of therapy to bone marrow abnormality ranged from 11 to 192 months (median, 58). Thirty-three patients had been previously treated for lymphoproliferative diseases, 29 for carcinoma, and three for a nonneoplastic disorder. Approximately 30% of the cases presenting in the MDS phase evolved to AML in one to 12 months (median, 3.5). The AML in 49% of the cases was not readily classified according to French-American-British (FAB) criteria; the primary difficulty in classification related to the involvement of multiple cell lines. Among the cases that could be classified, all FAB types were represented except for M1; M2 was the most frequent type. Clonal chromosome abnormalities were found in marrow specimens from 22 of 24 (92%) patients studied with G banding; 11 had abnormalities of chromosomes 5 and/or 7. The median survival for all patients was four months with no significant difference between those treated and not treated with antileukemic therapy. The median survival was three months for the patients presenting with AML, six months for the patients with AML following an MDS, and four months for the patients with an MDS that did not evolve to AML. The findings in the present study suggest that there are three stages of therapy-related panmyelosis: (1) pancytopenia with associated myelodysplastic changes, (2) a frank MDS, and (3) overt AML. Many patients will present in the stage of overt AML that differs from de novo AML primarily by the high incidence of trilineage involvement, difficulty in classification, frequent cytogenetic abnormalities, and poor response to antileukemic therapy.},
doi = {},
journal = {Blood; (United States)},
number = ,
volume = 6,
place = {United States},
year = 1985,
month = 6
}
  • We conducted a study to estimate the maximum tolerated dose (MTD) of I-131-anti-CD45 antibody (Ab; BC8) that can be combined with a standard reduced-intensity conditioning regimen before allogeneic hematopoietic cell transplantation. Fifty-eight patients older than 50 years with advanced acute myeloid leukemia (AML) or high-risk myelodysplastic syndrome (MDS) were treated with (131)I-BC8 Ab and fludarabine plus 2 Gy total body irradiation. Eighty-six percent of patients had AML or MDS with greater than 5% marrow blasts at the time of transplantation. Treatment produced a complete remission in all patients, and all had 100% donor-derived CD3(+) and CD33(+) cells in the bloodmore » by day 28 after the transplantation. The MTD of I-131-BC8 Ab delivered to liver was estimated to be 24 Gy. Seven patients (12%) died of nonrelapse causes by day 100. The estimated probability of recurrent malignancy at 1 year is 40%, and the 1-year survival estimate is 41%. These results show that CD45-targeted radiotherapy can be safely combined with a reduced-intensity conditioning regimen to yield encouraging overall survival for older, high-risk patients with AML or MDS. This study was registered at www.clinicaltrials.gov as #NCT00008177.« less
  • No abstract prepared.
  • Twelve patients (two with de novo myelodysplastic syndrome (MDS), four with secondary MDS, five with de novo acute nonlymphocytic leukemia (ANLL), one with secondary ANLL) showed a 17p deletion resulting from translocations involving 17p: t(5;17)(p11;p11) in four cases, t(7;17)(p11;p11) in six cases, complex (5;17)(q23;p12) translocation with dicentric chromosome in one case, and t(17; )(p11-12; ) in the remaining patient. All these structural anomalies were observed in hypodiploid clones associated with total or partial monosomy of chromosomes 5 and 7 (12 cases), monosomy 12 (five cases), monosomy 3 (four cases), and monosomy 4 (three cases). Median survival was only 3.3 monthsmore » (range 3 days to 8 months). Striking features were observed in bone marrow mature granulocytes: all but one case had a pseudo-Pelger-Hut anomaly in a significant number of granulocytes, and eight patients had granulocytes with reduced size and clear cytoplasmic vacuoles. Careful cytological review of 51 patients with MDS or ANLL and various cytogenetic anomalies was performed for comparison: vacuolated granulocytes were a very uncommon finding. On the other hand, eight patients had a pseudo-Pelger-Hut anomaly, which correlated significantly with total monosomy 17 in these patients. A possible correlation between cytological anomalies and cytogenetic data is discussed, and the role of 17p in the nuclear segmentation of granulocytes is stressed.« less
  • Monosomy 7 and interstitial deletions in the long arm of chromosome 7 (-7/7q-) is a common nonrandom chromosomal abnormality found frequently in myeloid disorders including acute myeloid leukemia (AML), myelodysplastic syndrome (MDS), and juvenile myelomonocytic leukemia (JMML). Using a short probe-based microarray comparative genomic hybridization (mCGH) technology, we identified a common microdeletion cluster in 7q21.3 subband, which is adjacent to 'hot deletion region' thus far identified by conventional methods. This common microdeletion cluster contains three poorly characterized genes; Samd9, Samd9L, and a putative gene LOC253012, which we named Miki. Gene copy number assessment of three genes by real-time PCR revealedmore » heterozygous deletion of these three genes in adult patients with AML and MDS at high frequency, in addition to JMML patients. Miki locates to mitotic spindles and centrosomes and downregulation of Miki by RNA interference induced abnormalities in mitosis and nuclear morphology, similar to myelodysplasia. In addition, a recent report indicated Samd9 as a tumor suppressor. These findings indicate the usefulness of the short probe-based CGH to detect microdeletions. The three genes located to 7q21.3 would be candidates for myeloid tumor-suppressor genes on 7q.« less
  • During 1982 and 1983, 4496 new cases were recorded in the French Registry of acute leukemia and myelodysplastic syndromes by the French Group of Hematologic Morphology. This cooperative group associated members of 37 university centers spread throughout France; these centers handle the overwhelming majority of acute leukemias diagnoses. The cases were all classified according to FAB guidelines. Two thousand four hundred ninety-nine cases of acute myeloid leukemia were recorded, with similar total recruitment and distribution by cytologic subclass for both years. Hemogram data analysis revealed significant differences between different classes for certain parameters, particularly leukocytosis. A greater proportion of themore » acute myelogenous leukemias (AMLs) secondary to chemotherapy and/or radiotherapy (n = 145) were unclassifiable according to the French-American-British (FAB) system than the de novo AMLs (n = 1954). Eight hundred twenty cases of myelodysplastic syndromes were analyzed. Their frequency was underestimated due to optional reporting during the first year and the less favorable position of the university centers for recruiting these syndromes. The characteristics of the hemograms were established for acquired idiopathic sideroblastic anemia (n = 107), refractory anemia with excess blasts (RAEB) (n = 329), chronic myelomonocytic leukemia (n = 129) and RAEB in transformation (n = 65). Analysis of the 1177 acute lymphoblastic leukemias (ALLs) recorded showed good stability from one year to the next in terms of numbers of cases and distribution in the subclasses L1, L2, and L3. The distribution among these three subclasses by age also was determined. For L1 and L2 the hemogram data were examined separately for adults and children. The study of 74 cases of type L3 ALL enabled us to detail the hematologic presentation of this rare form of leukemia.« less