scholarly journals Hematologic abnormalities in Fanconi anemia: an International Fanconi Anemia Registry study [see comments]

Blood ◽  
1994 ◽  
Vol 84 (5) ◽  
pp. 1650-1655 ◽  
Author(s):  
A Butturini ◽  
RP Gale ◽  
PC Verlander ◽  
B Adler-Brecher ◽  
AP Gillio ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Confidence Interval ◽  
Myelodysplastic Syndrome ◽  
Fanconi Anemia ◽  
Myelogenous Leukemia ◽  
Registry Study ◽  
Cytogenetic Abnormalities ◽  
Risk Of Death ◽  
Acute Myelogenous ◽  
Actuarial Risk

We analyzed data from 388 subjects with Fanconi anemia reported to the International Fanconi Anemia Registry (IFAR). Of those, 332 developed hematologic abnormalities at a median age of 7 years (range, birth to 31 years). Actuarial risk of developing hematopoietic abnormalities was 98% (95% confidence interval, 93% to 99%) by 40 years of age. Common hematologic abnormalities were thrombocytopenia and pancytopenia. These were often associated with decreased bone marrow (BM) cellularity (75% of cases studied). Clonal cytogenetic abnormalities developed in 23 of 68 persons with BM failure who had adequate studies. Actuarial risk of clonal cytogenetic abnormalities during BM failure was 67% (47% to 87%) by 30 years of age. Fifty-nine subjects developed myelodysplastic syndrome (MDS) or acute myelogenous leukemia (AML). Actuarial risk of MDS or AML was 52% (37% to 67%) by 40 years of age. Risk was higher in persons with than in those without a prior clonal cytogenetic abnormality (3% [0% to 9%] v 35% [0% to 79%]; P = .006). One hundred twenty persons died of hematologic causes including BM failure, MDS or AML and treatment related complications. Actuarial risk of death from hematologic causes was 81% (67% to 90%) by 40 years of age.

scholarly journals Hematologic abnormalities in Fanconi anemia: an International Fanconi Anemia Registry study [see comments]

Blood ◽  
1994 ◽  
Vol 84 (5) ◽  
pp. 1650-1655 ◽  
Author(s):  
A Butturini ◽  
RP Gale ◽  
PC Verlander ◽  
B Adler-Brecher ◽  
AP Gillio ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Confidence Interval ◽  
Myelodysplastic Syndrome ◽  
Fanconi Anemia ◽  
Myelogenous Leukemia ◽  
Registry Study ◽  
Cytogenetic Abnormalities ◽  
Risk Of Death ◽  
Acute Myelogenous ◽  
Actuarial Risk

Abstract We analyzed data from 388 subjects with Fanconi anemia reported to the International Fanconi Anemia Registry (IFAR). Of those, 332 developed hematologic abnormalities at a median age of 7 years (range, birth to 31 years). Actuarial risk of developing hematopoietic abnormalities was 98% (95% confidence interval, 93% to 99%) by 40 years of age. Common hematologic abnormalities were thrombocytopenia and pancytopenia. These were often associated with decreased bone marrow (BM) cellularity (75% of cases studied). Clonal cytogenetic abnormalities developed in 23 of 68 persons with BM failure who had adequate studies. Actuarial risk of clonal cytogenetic abnormalities during BM failure was 67% (47% to 87%) by 30 years of age. Fifty-nine subjects developed myelodysplastic syndrome (MDS) or acute myelogenous leukemia (AML). Actuarial risk of MDS or AML was 52% (37% to 67%) by 40 years of age. Risk was higher in persons with than in those without a prior clonal cytogenetic abnormality (3% [0% to 9%] v 35% [0% to 79%]; P = .006). One hundred twenty persons died of hematologic causes including BM failure, MDS or AML and treatment related complications. Actuarial risk of death from hematologic causes was 81% (67% to 90%) by 40 years of age.

Loss of the Y Chromosome: An Age-Related or Clonal Phenomenon in Acute Myelogenous Leukemia/Myelodysplastic Syndrome?

2008 ◽  
Vol 132 (8) ◽  
pp. 1329-1332
Author(s):  
Anna K. Wong ◽  
Belle Fang ◽  
Ling Zhang ◽  
Xiuqing Guo ◽  
Stephen Lee ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Myelodysplastic Syndrome ◽  
Y Chromosome ◽  
Acute Myelogenous Leukemia ◽  
Myelogenous Leukemia ◽  
Related Phenomenon ◽  
Patients Âgés ◽  
Age Related ◽  
Acute Myelogenous ◽  
Bone Marrow Analysis

Abstract Context.—The clinical association between loss of the Y chromosome and acute myelogenous leukemia and myelodysplastic syndrome (AML/MDS) has been debated because both phenomena are related to aging. A prior publication suggests that loss of the Y chromosome in more than 75% of cells may indicate a clonal phenomenon that could be a marker for hematologic disease. Objective.—To evaluate the relationship between loss of the Y chromosome and AML/MDS. Design.—A retrospective review of cytogenetic reports of 2896 male patients ascertained from 1996 to 2007 was performed. Results were stratified based on the percentage of cells missing the Y chromosome and were correlated with patients' ages and bone marrow biopsy reports through logistic regression analysis with adjustment for age. Results.—Loss of the Y chromosome was found in 142 patients. Of these, 16 patients demonstrated myeloid disease, with 2 cases of AML and 14 cases of MDS. An increased incidence (P < .05) of AML/MDS was seen only in the group composed of 8 patients with complete loss of the Y chromosome in all karyotyped cells (1 case of AML and 7 cases of MDS). Conclusion.—Loss of the Y chromosome appears to be primarily an age-related phenomenon. However, in individuals in which all cells on cytogenetic analysis showed loss of the Y chromosome, there was a statistically significant increase in AML/MDS, suggesting that the absence of any normal-dividing cells in a bone marrow analysis may be indicative of AML/MDS.

Cytogenetic Abnormalities in Primary Myelodysplastic Syndrome Are Highly Predictive of Outcome After Allogeneic Bone Marrow Transplantation

Blood ◽  
1998 ◽  
Vol 92 (6) ◽  
pp. 1910-1917 ◽  
Author(s):  
Thomas J. Nevill ◽  
Henry C. Fung ◽  
John D. Shepherd ◽  
Douglas E. Horsman ◽  
Stephen H. Nantel ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Bone Marrow Transplantation ◽  
Myelodysplastic Syndrome ◽  
Marrow Transplantation ◽  
Allogeneic Bone Marrow Transplantation ◽  
Allogeneic Bone Marrow ◽  
Myelogenous Leukemia ◽  
Allogeneic Bone ◽  
Cytogenetic Abnormalities ◽  
Poor Risk

Abstract Allogeneic bone marrow transplantation (BMT) is the only curative therapy available for patients with myelodysplastic syndrome (MDS). In an attempt to identify prognostic factors influencing outcome, we collected data retrospectively on 60 consecutive adult patients who had undergone BMT at our center for primary MDS or acute myelogenous leukemia evolving from preexisting primary MDS (sAML). Patients were divided into subgroups according to cytogenetic abnormalities based on a recently described International MDS Workshop categorization system. The 7-year actuarial event-free survival (EFS), relapse rate, and nonrelapse mortality (NRM) for all patients were 29% (95% confidence interval [CI], 16% to 43%), 42% (CI, 24% to 67%), and 50% (CI, 37% to 64%), respectively. The EFS for the good-, intermediate-, and poor-risk cytogenetic subgroups were 51% (CI, 30% to 69%), 40% (CI, 16% to 63%), and 6% (CI, 0% to 24%), respectively (P= .003). The corresponding actuarial relapse rates were 19% (CI, 6% to 49%), 12% (CI, 2% to 61%), and 82% (CI, 48% to 99%), respectively (P = .002) with no difference in NRM between the subgroups. Univariate analysis showed cytogenetic category, French-American-British (FAB) subtype, and graft-versus-host disease (GVHD) prophylaxis used to be predictive of relapse and EFS. In multivariate analysis, only the cytogenetic category was predictive of EFS, with the relative risk of treatment failure for the good-, intermediate-, and poor-risk cytogenetic subgroups being 1.0, 1.5, and 3.5, respectively (P = .004). For adults with primary MDS and sAML, even after BMT, poor-risk cytogenetics are predictive of an unfavorable outcome; novel treatment strategies will be required to improve results with allogeneic BMT in this patient population. © 1998 by The American Society of Hematology.

scholarly journals Long-term bone marrow culture in persons with Fanconi anemia and bone marrow failure

Blood ◽  
1994 ◽  
Vol 83 (2) ◽  
pp. 336-339 ◽  
Author(s):  
A Butturini ◽  
RP Gale
Keyword(s):  
Bone Marrow ◽  
Fanconi Anemia ◽  
Autosomal Recessive ◽  
Autosomal Recessive Disease ◽  
Bone Marrow Failure ◽  
Myelogenous Leukemia ◽  
Acute Myelogenous ◽  
Nonadherent Cells

Abstract Fanconi anemia is an autosomal recessive disease characterized by a high risk of developing bone marrow (BM) failure and acute myelogenous leukemia. We studied growth of hematopoietic progenitor cells in long- term BM culture (LTBMC) in 8 persons with Fanconi anemia and BM failure. Although LTBMC were initiated with very few BM cells, an adherent layer formed in cultures from 7 persons. In these cultures, the number of nonadherent cells increased for 10 to 15 days. Cell growth continued until cultures were terminated at day 35 to 40. During the first 2 weeks of culture, most nonadherent cells were differentiated myeloid cells. By days 35 to 40, the adherent layer contained cells able to initiate secondary LTBMCs. These data indicate that hematopoietic precursors cells able to proliferate and differentiate in vitro are present in the BM of persons with Fanconi anemia and BM failure. They suggest that mechanisms other than absent precursor cells are responsible for BM failure in Fanconi anemia.

Analysis of the Incidence of Treatment-Related Myelodysplastic Syndrome and Acute Myelogenous Leukemia in Registration and Compassionate-Use Trials of Ibritumomab Tiuxetan Radioimmunotherapy (RIT).

Blood ◽  
2006 ◽  
Vol 108 (11) ◽  
pp. 485-485 ◽  
Author(s):  
Myron S. Czuczman ◽  
Christos Emmanouilides ◽  
Mohamed Darif ◽  
Thomas E. Witzig ◽  
Leo I. Gordon ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Myelodysplastic Syndrome ◽  
Acute Myelogenous Leukemia ◽  
Myelogenous Leukemia ◽  
Purine Nucleoside ◽  
Low Grade ◽  
Compassionate Use ◽  
Ibritumomab Tiuxetan ◽  
Acute Myelogenous ◽  
Effects Of Radiation

Abstract Radioimmunotherapy (RIT) is a therapeutic modality indicated for the treatment of patients with relapsed or refractory low-grade, follicular, or transformed non-Hodgkin’s lymphoma (NHL), where the mechanism of action involves the intrinsic activity of the monoclonal antibody and the cytotoxic effects of radiation. The primary toxicity is a late-occurring, transient, and reversible myelosuppression. Because of concerns regarding the long-term effects of radiation on the bone marrow, we investigated the incidence of treatment-related myelodysplastic syndrome (t-MDS) and treatment-related acute myelogenous leukemia (t-AML) after ibritumomab tiuxetan RIT. A total of 746 patients with NHL were treated with the ibritumomab tiuxetan regimen in registration and compassionate-use trials between 1996 and 2002. Patients had a median age of 61 years (range, 24–87) and had received a median of 3 prior therapies (range, 0–9+). The crude incidence of t-MDS or t-AML was 2.3% (17/746), with an incidence of 4.7% (10/211) in patients enrolled in registration trials and of only 1.3% (7/535) in patients included in the compassionate-use trial, with a median follow-up of 5.7 and 3.5 years, respectively. These malignancies were documented at a median of 5.6 years (range, 1.2–13.9) after the diagnosis of NHL and 1.5 years (range, 0.1–5.8) after RIT. The annualized rates were 0.3% (95% CI, 0.2%–0.4%) a year after the diagnosis of NHL and 0.7% (95% CI, 0.4%–1.0%) a year after RIT. Cox multivariate regression analysis found that previous treatment with a purine nucleoside analog was a significant risk factor for t-MDS or t-AML (hazard ratio, 3.9 [95% CI, 1.5–10.4]; P = .006). All patients in whom t-MDS or t-AML developed and in whom cytogenetic data were available (n = 15) had multiple cytogenetic aberrations, commonly of chromosomes 5 and 7, suggesting an association with previous exposure to chemotherapy. There were documented bone marrow cytogenetic abnormalities before treatment in 2 patients who developed t-MDS or t-AML. These data suggest that the annualized incidence of t-MDS or t-AML following ibritumomab tiuxetan RIT is consistent with that expected on the basis of the patients’ history of treatment for NHL. Cytogenetic testing before administration of RIT may identify existing chromosomal abnormalities in previously treated patients, particularly in those who have been treated with alkylating agents and/or purine nucleoside analogs and who are thereby at a higher risk for t-MDS or t-AML.

Bone Marrow Transplantation for Children Less Than 2 Years of Age With Acute Myelogenous Leukemia or Myelodysplastic Syndrome

Blood ◽  
1998 ◽  
Vol 92 (10) ◽  
pp. 3546-3556
Author(s):  
Ann E. Woolfrey ◽  
Ted A. Gooley ◽  
Eric L. Sievers ◽  
Laurie A. Milner ◽  
Robert G. Andrews ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Myelodysplastic Syndrome ◽  
Acute Myelogenous Leukemia ◽  
Chronic Gvhd ◽  
Disease Free Survival ◽  
Myelogenous Leukemia ◽  
Acute Myelogenous ◽  
First Remission ◽  
First Relapse ◽  
Disease Free

We analyzed results of 40 infants less than 2 years of age who received bone marrow transplants (BMT) between May 1974 and January 1995 for treatment of acute myelogenous leukemia (AML; N = 34) or myelodysplastic syndrome (MDS; N = 6) to determine outcome and survival performance. Among the AML patients, 13 were in first remission, 9 were in untreated first relapse or second remission, and 12 were in refractory relapse. Patients were conditioned with cyclophosphamide in combination with either total body irradiation (TBI; N = 29) or busulfan (N = 11). Source of stem cells included 6 autologous donors, 15 HLA genotypically identical siblings, 14 haploidentical family members, and 5 unrelated donors. Graft-versus-host disease (GVHD) prophylaxis was methotrexate (MTX) for 17, MTX plus cyclosporine (CSP) for 14, or CSP plus prednisone for 3. Incidence of severe (grade 3-4) regimen-related toxicity was 10% and transplant-related mortality was 10%. Acute GVHD (grades II-III) occurred in 39% of allogeneic patients, and chronic GVHD developed in 40%. Relapse, the most significant problem for patients in this study, occurred in 1 MDS patient and 23 AML patients and was the cause of death for 19 patients. The 2-year probabilities of relapse are 46%, 67%, and 92%, respectively, for patients transplanted in first remission, untreated first relapse or second remission, and relapse. One MDS and 8 AML patients received second marrow transplants for treatment of relapse, and 5 of these survive disease-free for more than 1.5 years. All 6 MDS patients and 11 of 34 AML patients survive more than 1.5 years later. The 5-year probabilities of survival and disease-free survival are 54% and 38% for patients transplanted in first remission and 33% and 22% for untreated first relapse or second remission. None of the patients transplanted with refractory relapse survive disease-free. Outcome was significantly associated with phase of disease at transplantation and pretransplant diagnosis of extramedullary disease. Long-term sequelae included growth failure and hormonal deficiencies. Survival performance was a median of 100% (80% to 100%) and neurologic development for all survivors was appropriate for age. This study indicates that infants with AML have similar outcome after BMT compared with older children and that BMT should be performed in first remission whenever possible. In addition, allogeneic BMT provides effective therapy for the majority of infants with MDS.

scholarly journals Myelofibrosis in Cats with Myelodysplastic Syndrome and Acute Myelogenous Leukemia

1988 ◽  
Vol 25 (2) ◽  
pp. 154-160 ◽  
Author(s):  
J. T. Blue
Keyword(s):  
Bone Marrow ◽  
Myelodysplastic Syndrome ◽  
Causal Relationship ◽  
Acute Myelogenous Leukemia ◽  
Myelogenous Leukemia ◽  
Lymphoid Follicles ◽  
Acute Myelogenous

Bone marrow sections from 44 cats with myelodysplastic syndrome (MDS) or acute myelogenous leukemia (AML) were graded for reticulin content using light microscopic methods. Twenty-seven (61%) of the cats had slight to marked reticulin myelofibrosis. The association of myelofibrosis with possible pathogenetic factors, including megakaryocyte count, intramedullary lymphoid follicles, hemosiderin content, and FeLV antigenemia, was examined. No evidence was found that indicated a causal relationship between myelofibrosis and any of these factors.

Prevalence and clinical characteristics of myelodysplastic syndrome with bone marrow eosinophilia or basophilia

Blood ◽  
2003 ◽  
Vol 101 (9) ◽  
pp. 3386-3390 ◽  
Author(s):  
Takafumi Matsushima ◽  
Hiroshi Handa ◽  
Akihiko Yokohama ◽  
Jun Nagasaki ◽  
Hiromi Koiso ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Myelodysplastic Syndrome ◽  
Clinical Characteristics ◽  
De Novo ◽  
Chromosomal Abnormalities ◽  
Bone Marrow Cells ◽  
Myelogenous Leukemia ◽  
International Prognostic Scoring System ◽  
Differential Count ◽  
Acute Myelogenous

By retrospectively analyzing 288 patients with de novo myelodysplastic syndrome (MDS), we sought to determine the prevalence and clinical characteristics of bone marrow eosinophilia and basophilia that were detected at presentation. Bone marrow eosinophilia and basophilia were defined as a differential count of each cell type exceeding 5.0% and 1.0%, respectively. Of 288 patients with MDS, 36 (12.5%) fulfilled this criterion for bone marrow eosinophilia (MDS-Eos); 34 patients (11.8%) showed basophilia (MDS-Bas), and 11 (3.8%) satisfied both criteria (MDS-EosBas). The remaining 229 patients had neither eosinophilia nor basophilia in their bone marrow (MDS−/−) at presentation. Cytogenetic analysis was carried out on unstimulated bone marrow cells obtained from 264 patients. When the cytogenetic categorization of the IPSS (International Prognostic Scoring System) for MDS was applied, significantly higher numbers of MDS-Eos and MDS-Bas patients had chromosomal abnormalities carrying intermediate or poor prognosis, compared with the MDS−/− patients. Specific chromosomal abnormalities and complex karyotypes were associated with MDS-Eos and/or MDS-Bas. In accordance with these results, the overall survival rate was significantly lower, and the evolution to acute myelogenous leukemia (AML) occurred more frequently in the MDS-Eos and MDS-Bas than in the MDS−/− patients. Multivariate analysis demonstrated that bone marrow basophilia was an independent risk factor for evolution to AML. Our study indicates that bone marrow eosinophilia and basophilia in patients with MDS predict a poorer prognosis.

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