A total of 109 patients with myelodysplastic syndromes (MDS) was analyzed to determine the clinical and pathologic features of the five recently defined French-American-British Cooperative Group (FAB) subtypes, and to assess the utility of this classification system in predicting survival, evolution to acute nonlymphocytic leukemia (ANLL), and cause of death All patients with MDS presented with anemia; additional cytopenias were present in patients with refractory anemia with excess blasts (RAEB), chronic myelomonocytic leukemia (CMML) and refractory anemia with excess blasts in transformation to ANLL (RAEB/Tr) Thirty-two patients received some form of antileukemic therapy for MDS ANLL developed in 16 of the 77 remaining untreated patients, including 18% (2/11), 0% (0/21), 22% (5/23), 33% (2/6), and 44% (7/16) of patients with refractory anemia (RA), refractory anemia with ring sideroblasts (RARS), RAEB, CMML, and RAEB/Tr, respectively (P = 002) The FAB subtype was highly predictive of survival with median survivals ranging from 71 months for RARS to 5 months for RAEB/Tr (P = less than 00001) Patients with RAEB, CMML, and RAEB/Tr frequently died of direct consequences of MDS, while patients with RA and especially RARS generally survived or died from unrelated disorders (P = less than 00001) MDS encompass a spectrum of disorders RA and RARS, are relatively indolent and often do not lead to the patient's demise RAEB, CMML, and RAEB/Tr are aggressive disorders which are often responsible for the patient's death whether or not actual progression to overt leukemia occurs FAB subtype predicts survival, evolution to ANLL, and cause of death, although the five morphologic subtypes appear to separate into only two disease groups, especially with regard to survival and cause of death

Myelodysplastic syndromes. A clinical and pathologic analysis of 109 cases

Clinicomorphological features of myelodysplastic syndromes, Antonio Pagliuca and Ghulam J. Mufti FAB and MIC classification of myelodysplastic syndromes - points of controversy, John M. Bennett incidence and epidemiology of the myelodysplastic syndromes, R. A. Cartwright pathogenesis and evolution of refractory anaemia, A. Jacobs and D. Bowen the relationship between acute myeloid leukaemia and myelodysplasia, D. A. G. Galton and F. M. C. Brito-Babapulle chronic myelomonocytic leukaemia, R. Zittoun transformation of the myelodysplastic syndromes to acute leukaemia, Guido J. Tricot et al immunological abnormalities in myelodysplastic syndromes, T. J. Hamblin chromosomal abnormalities in primary myelodysplastic syndromes, S. Heim and F. Mitelman chromosomal abnormalities in secondary acute myeloid leukaemia and the myelodysplastic syndromes, Roland Berger and Georges Flandrin biological significance of chromosomal abnormalities in the myelodysplastic syndromes, Maya Thangavelu and Michelle M. Le Beau the molecular biology of myelodysplastic syndromes (preleukaemia), D. Mark Layton myelodysplastic syndrome - culture studies and their implications for therapy, Ronald L. Paquette and H. Phillip Koeffler primary myelodysplastic syndrome - prognostic value of FAB classification, scoring systems, bone-marrow histology and karyotypic analysis. Ghulam J. Mufti the role of colony-stimulating factors in the therapy of myelodysplastic syndromes, Stephen A. Cannastra and James D. Griffin.

/pdf/the-myelodysplastic-syndromes-5f4nynnpow.pdf

The myelodysplastic syndromes.

Association of non-Hodgkin's lymphoma and second neoplasms

Purpose: Current treatment of the Ewing sarcoma family of tumors (ESFT) includes intensive multiagent chemotherapy with topoisomerase II inhibitors, alkylating agents, and granulocyte colony-stimulating factor (G-CSF). This treatment approach has been associated with myelodysplasia and acute myeloid leukemia. Because macrocytosis and thrombocytopenia are distinctive features of myelodysplasia, the authors evaluated a cohort of patients treated for ESFT to determine the degree and duration of macrocytosis and thrombocytopenia and their relation with the development of therapy-related hematologic malignancies. Patients and Methods: The study group consisted of 73 patients with ESFT treated on two consecutive protocols (EW92 and EW87). Both chemotherapy regimens incorporated the same agents but differed in cumulative drug dose, dose per course, and the use of G-CSF. Platelet counts and the mean corpuscular volume (MCV) of erythrocytes were determined at diagnosis and during follow-up visits after completion of treatment. Results: Patients in the EW92 group had significantly greater MCVs after treatment than did the less intensively treated EW87 group. These changes persisted throughout the 40-month observation period. Patients in the EW92 group also had lesser mean platelet counts after treatment than those in the EW87 group. MCV differences (from baseline) were inversely related to platelet counts. The cumulative incidence of treatment-related acute myeloid leukemia was 7.8% ± 4.7% at 4 years in the EW92 group and zero in the EW87 group. Conclusion: Patients treated for ESFT with intensive chemotherapy that includes large doses of alkylators, topoisomerase II inhibitors, and G-CSF characteristically have persistently elevated MCVs and decreased platelet counts after completion of therapy. These hematologic abnormalities may represent stem cell damage, predisposing patients to myelodysplasia and acute myeloid leukemia, but further study is needed to establish this relation.

Hematologic abnormalities and acute myeloid leukemia in children and adolescents administered intensified chemotherapy for the Ewing sarcoma family of tumors.

Peripheral blood changes preceding therapy-related leukemia were studied in 105 patients who had received cytotoxic therapy, 53 for Hodgkin's disease and 52 for other cancers. Preleukemic anomalies were observed in 74.3% of the cases, appearing after a mean interval of 68.7 months after diagnosis of the initial cancer. This interval was only 57.5 months in patients aged 50 years or older and only 42.3 months in patients with Hodgkin's disease having received cytotoxic therapy for 6 months or less. The first changes most frequently observed were pancytopenia (24.8%) and isolated erythrocyte abnormalities such as anemia or macrocytosis (18.1%). Involvement of two cell lines, isolated thrombocytopenia or leukopenia, circulating immature cells, monocytosis, leukocytosis, or thrombocytosis were also observed. Therapy-related myelodysplastic syndrome was recognized in 19 patients and myelofibrosis in 3. Median duration of the preleukemic phase was 6 months; 9 months in cases of isolated erythrocyte involvement and 5 months in the other cases. Myelomonocytic or monoblastic leukemia appeared less frequently when the first sign involved erythrocytes only. Hematological surveillance thus appears necessary in all patients having received cytotoxic therapy. Bone marrow study with cytogenetic examination should be performed in cases of persistent peripheral blood abnormalities.

Preleukemic changes in cases of nonlymphocytic leukemia secondary to cytotoxic therapy. Analysis of 105 cases.

Summary

Clinical and haematological features of 13 patients with secondary myelodysplastic syndromes (MDS) were studied. MDS developed subsequent to chemotherapy and/or radiotherapy for various haematological or non-haemato-logical diseases. In six cases, the first sign was a persistently increased mean cell volume (MCV) and a macrocytosis preceding from 6 to 18 months the appearance of severe anaemia or acute leukaemia. In five cases, the initial finding was a macrocytic anaemia. Dysmyelopoiesis was a constant and prominent feature of the bone marrow smears at some time during the course of the disease. Two cases without macrocytosis at any time directly developed overt acute leukaemia.

Myelodysplasia and leukaemia related to chemotherapy and/or radiotherapy--a haematological study of 13 cases. Value of macrocytosis as an early sign of bone marrow injury.

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Myelodysplasia and leukaemia related to chemotherapy and/or radiotherapy--a haematological study of 13 cases. Value of macrocytosis as an early sign of bone marrow injury.