Therapy-related myelodysplasia and/or acute myeloid leukaemia after autologous haematopoietic progenitor cell transplantation in a prospective single centre cohort of 221 patients (original) (raw)
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Bone Marrow Transplantation, 1999
Secondary myelodysplastic syndromes (MDS) are increasingly being reported after autologous transplantation. Transient dysplastic changes have also been observed after this type of treatment. However, to the best of our knowledge no systematic morphological analysis has been perfomed to determine the influence of stem cell transplantation on bone marrow morphology. In 53 patients undergoing autologous transplantation, we evaluated the bone marrow, before and 6 and 12 months after the transplant, in order to analyze the appearance of dyshemopoietic changes, assessed according to a pre-established score. We also studied 25 bone marrow samples obtained at the time of diagnosis, prior to treatment, but we did not find morphological atypia. Six months after transplant, cellularity and thrombopoiesis had decreased in 38% and 49% of patients respectively, although 1 year after the process they were normal in most cases. Myelodysplasia was already present in bone marrow before transplantation and continued to be in evidence for a long time afterwards. This suggests that chemotherapy and radiotherapy used prior to transplantation are responsible for dysplastic changes. The myeloid line was the most affected with 100% of patients showing dysgranulopoiesis 1 year after autografting. Cytopenias were observed in 51% and 44% of patients 6 and 12 months after transplantation. Moreover, concomitant presence of cytopenia and myelodysplasia was observed in 37.7% of patients at 6 months after transplantation and 25% at 12 months, and therefore they could be diagnosed with MDS. These data contrast with the incidence of secondary MDS reported in earlier publications. According to these findings, the value of the French-American-British Co-operative Group criteria for the diagnosis of MDS following autologous transplantation is questionable. Moreover, since dyshemopoietic features are almost always present after autologous transplant, morphological criteria are not useful for early
Sequential cytogenetic study of patients after bone marrow transplantation
Cancer Genetics and Cytogenetics, 1994
Thirty-one patients {19 males and 12 females; mean age 23.9 years, range 4-41 years) were treated with bone marrow transplantation {BMT) after intensive chemoradiotherapy. Their diagnoses were as follows: chronic myeloid leukemia {CML) in 13, acute myeloid leukemia {AML) in seven, acute lymphocytic leukemia CALL) in six, myelodysplastic syndrome {MDS) in two, aplastic anemia (AA) in two, and Fanconi anemia {FA) in one. Allogeneic BMT was performed in 28 cases {17 donors were of like sex, 11 were of unlike sex), one patient received syngenic transplant, and one received transplant of cells obtained from an unrelated donor through a computerized international registry in London. Autologous BMT was performed in three patients. BM cells were analyzed cytogenetically at diagnosis, before and serially after BMT {three to nine times). Follow-up ranged from 2 to 55.5 months. Cytogenetic examination was a very useful method/'or monitoring posttransplantation course in patients with CML or in those who received BM ceils of unlike sex. Results of concomitant cytogenetic examinations are reported in detail.
Bone Marrow Transplantation, 1998
of myelodysplasia or secondary AML 5,6 and consequently a shortened survival. 7 Indeed, the development of cytogenetic abnormalities and MDS following ABMT for lymphoma We undertook a retrospective review of all 76 patients with AML transplanted between August 1986 and appear to be related to exposure to alkylating agents during conventional-dose chemotherapy rather than the high-March 1995 at our center. All patients received melphalan (140-160 mg/m 2), etoposide (60 mg/kg) and total dose regimen. 8 As induction and consolidation chemotherapy for AML body irradiation. All patients had bone marrow cytogenetic analysis at regular intervals following ABMT. do not generally include alkylating agents, we were interested in determining the incidence and significance of new The primary study end point was the development of the new cytogenetic abnormalities. Secondary end isolated cytogenetic abnormalities after ABMT for AML. points were the development of myelodysplasia (MDS) or AML. Sixty-two of 77 patients were alive at least 6 months post transplant. Cytogenetic abnormalities Patients and methods developed in 7/62 patients (11%) following ABMT. No patients demonstrated MDS or AML. At a median of We evaluated all patients undergoing ABMT for AML at our center between 1986 and 1995 to determine the fre-30 months after development of the cytogenetic abnormality, only one patient developed features suggestive quency and clinical significance of new clonal karyotypic abnormalities following transplantation. Patients Ͻ61 years but not diagnostic of MDS. All seven patients remain alive and leukemia-free up to 70 months after detection of age with ECOG performance status Ͻ2 were candidates for ABMT. Patients with persistent cytogenetic abnormali-of the abnormal clone. There was no increased incidence of cytogenetic abnormalities developing in patients ties or morphologic evidence of myelodysplasia following induction therapy were not eligible for ABMT. Intensive receiving a purged autograft. New cytogenetic abnormalities are frequent following ABMT for AML but do therapy and autotransplantation were performed in first or subsequent remission or early relapse with a marrow auto-not appear to predict development of myelodysplasia or acute myeloid leukemia. These abnormalities may relate graft collected in morphologic and cytogenetic remission. The intensive therapy regimen consisted of intravenous to use of total body radiation as part of the high-dose therapy. melphalan (140-160 mg/m 2), etoposide (VP-16) (60 mg/kg) and total body irradiation (TBI). The etoposide was Keywords: bone marrow transplantation; cytogenetics; acute myeloid leukemia; myelodysplasia administered as an infusion over 5 h for patients with good cardiac function and over 32 h for patients with left ventricular ejection fraction Ͻ45%. Patients in first complete remission were given a single fraction of TBI at a median Clonal cytogenetic abnormalities occur in the bone marrow rate of 50 cGy/min (range 30-60) to a total dose of 500 cGy of 50-90% of patients with acute myeloid leukemia (AML) while those in other disease states received six fractions of at the time of diagnosis and are strongly implicated in its 200 cGy administered at the same rate (total dose 1200 pathogenesis. 1,2 Furthermore, recurrence of the initial cGy). Patients were assessed at 3-monthly intervals for the malignant cytogenetic clone in the marrow of patients after first 2 years following ABMT and at 6-monthly intervals conventional-dose induction chemotherapy is usually assothereafter. Follow-up studies included a complete physical ciated with morphologic relapse. 3,4 examination, complete blood count and bone marrow aspir-New clonal cytogenetic abnormalities appearing after ation with cytogenetic analysis. Cytogenetic studies were conventional chemotherapy for lymphoma or other maligperformed according to standard methods with the karyonancies are generally felt to be associated with a high risk types described according to the international system for cytogenetic nomenclature (ISCN). 9 We defined new cytogenetic abnormalities following ABMT as persistent clonal
Clinical and laboratory features of de novo acute myeloid leukaemia with trilineage myelodysplasia
British Journal of Haematology, 1987
Primary myelodysplastic syndromes progress to acute myeloid leukaemia (AML) in about 30% of cases. We have sought evidence of pre-existing trilineage myelodysplasia (TMDS) using the FAB criteria (1 982) in 160 consecutive cases of primary de novo AML. TMDS was found in 24 cases (1 5%) including two of 33 cases of M1 (6%). four of 40 cases of M2 (lo%), none of 18 cases of M3. five of 3 1 cases of M4 (1 5%). six of 30 cases of M5 (20%), all of six cases of M6 and one of two cases of M7.
Leukemia Research, 2012
In patients with myelodysplastic syndromes (MDS), chromosome anomalies are detected by conventional cytogenetic studies (CCS) and/or interphase fluorescence in situ hybridization (FISH) of bone marrow (BM) samples and provide prognostic and diagnostic information, which can direct therapy. Whether peripheral blood (PB) can be substituted for bone marrow in these cases and can provide the same information remains unknown. Concurrent BM and PB specimens collected from 100 patients with recently diagnosed MDS were studied using both CCS and FISH. While 68% of BM samples showed an abnormal karyotype by CCS, only 31% of PB samples were abnormal by CCS. In 12% of patients, FISH and CCS were discordant due to the inability of the FISH panel to detect all possible abnormalities. However, only one case (1%) had a cryptic abnormality detected by FISH. BM and PB FISH were discordant in 3% of cases, most likely due to the smaller clone size in PB vs. BM. While PB should not be substituted for BM at diagnosis, it is a viable alternative for monitoring patients using the appropriate FISH probe(s).
Immunophenotypic analysis of myelodysplastic syndromes
Background and Objectives. In contrast with hematologic malignancies in which the value of immunophenotypic studies is well established, information on the immunophenotypic characteristics of myelodysplastic syndromes (MDS) is scanty. The main goal of the present study was to explore the immunophenotypic differences between patients with MDS and normal individuals, including changes in distribution of cell lineages as well as phenotypic aberrations and blockades in cell maturation pathways.
British Journal of Haematology, 1996
Autologous bone marrow or peripheral blood stem cell transplantation may carry an increased risk of secondary myelodysplasia (MDS) and acute myeloid leukaemia (AML), which are already recognized as complications of conventional treatment for lymphoid malignancies. In order to ascertain whether it is possible to detect the evolution of such a clone at an early stage in its development we have studied X-chromosome inactivation patterns (XCIPs) in three informative females who developed abnormal myelopoiesis after high-dose chemotherapy and ABMT. In one patient transplanted for relapsed Hodgkin's disease a leukaemic clone comprising approximately 50% of the patient's myeloid cells was detectable by comparison of peripheral blood granulocyte and T-cell XCIPs when the full blood count and morphology were normal. She presented with AML 7 months later. In two patients transplanted for AML, XCIP analysis was complicated by constitutively skewed Lyonization patterns, nevertheless a progressive alteration could be demonstrated by serial analyses. In one patient a difference was detectable 28 months before presentation with MDS. In the other patient, despite evident mild pancytopenia and alterations in her XCIPs over the past 4 years, she has developed no definitive myelodysplastic features and oligoclonality due to stem cell failure cannot be excluded. These studies show that XCIPs can be used to predict development of MDS/AML in some patients, but the technique is limited by technical variability and frequent constitutional skewing in the haemopoietic system.
Biology of Blood and Marrow Transplantation, 2010
The rates of allogeneic stem cell transplantation (SCT) to treat the myelodysplastic syndromes (MDS) is continually increasing. However, given the growing arsenal of therapeutic options in parallel to deeper insight into the heterogeneity of this disorder, determining the indications for SCT in MDS remains a difficult task. The International Prognostic Scoring System (IPSS) serves as a guideline for therapeutic decisions, but many aspects (eg, interpretation of rare cytogenetic abnormalities, combinations of chromosomal alterations and/or molecular markers, variant clinical courses within distinct biological subgroups) remain the subject of continuous investigation. In an effort to achieve a more well-differentiated risk categorization, attempts have been made to perform a more detailed cytogenetic categorization, and the use of various fluorescein in situ hybridization (FISH) techniques has improved the description of aberrations. Multicenter initiatives have standardized multiparameter flow cytometry techniques for diagnosis of MDS. In advanced MDS, screening for molecular mutations can identify cases with a high transformation risk. Finally, the new World Health Organization classification system provides a more homogenous morphological categorization of MDS compared with the former French-American-British system. Consequently, in the near future, risk stratification in MDS might incorporate additional diagnostic tools and categorization systems aimed at improving the timing and indication for SCT in this complex disorder.