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1.
Lancet Haematol ; 10(3): e178-e190, 2023 Mar.
Article in English | MEDLINE | ID: mdl-36702138

ABSTRACT

BACKGROUND: Relapse remains high in patients with myelodysplastic syndrome-refractory anaemia with excess blasts (RAEB) or secondary acute myeloid leukaemia evolving from myelodysplastic syndrome undergoing allogeneic haematopoietic stem-cell transplantation (HSCT). We aimed to investigate whether granulocyte-colony stimulating factor (G-CSF) and decitabine plus busulfan-cyclophosphamide conditioning reduced relapse compared with busulfan-cyclophosphamide in this population. METHODS: We did an open-label, randomised, phase 3 trial at six hospitals in China. Eligible patients (aged 14-65 years) had myelodysplastic syndrome-RAEB or secondary acute myeloid leukaemia evolving from myelodysplastic syndrome, and an Eastern Cooperative Oncology Group performance status of 0-2 and HSCT comorbidity index of 0-2. Patients were randomly assigned (1:1) to receive G-CSF, decitabine, and busulfan-cyclophosphamide conditioning or busulfan-cyclophosphamide conditioning. Randomisation was done with permuted blocks (block size four) with no stratification and was implemented through an interactive web-based response system, which was independent of study site staff and investigators. G-CSF, decitabine, and busulfan-cyclophosphamide conditioning comprised G-CSF 5 µg/kg daily subcutaneously (days -17 to -10), decitabine 20 mg/m2 daily intravenously (days -14 to -10), busulfan 3·2 mg/kg daily intravenously (days -7 to -4), and cyclophosphamide 60 mg/kg daily intravenously (days -3 and -2). Busulfan-cyclophosphamide conditioning comprised the same dose and duration of busulfan and cyclophosphamide. The primary endpoint was 2 year cumulative incidence of relapse. All efficacy and safety endpoints were assessed in the intention-to-treat population. This trial is registered with ClinicalTrials.gov, NCT02744742; the trial is complete. FINDINGS: Between April 18, 2016, and Sept 30, 2019, 297 patients were screened for eligibility, 202 of whom were randomly assigned to G-CSF, decitabine, and busulfan-cyclophosphamide (n=101) or busulfan-cyclophosphamide (n=101) conditioning. 123 (61%) participants were male and 79 (31%) were female. Median follow-up was 32·4 months (IQR 10·0-43·0). The 2-year cumulative incidence of relapse was 10·9% (95% CI 5·8-17·9) in the G-CSF, decitabine, and busulfan-cyclophosphamide group and 24·8% (16·8-33·5) in the busulfan-cyclophosphamide group (hazard ratio 0·39 [95% CI 0·19-0·79]; p=0·011). Within 100 days after transplantation, the most common grade 3-4 adverse events in the G-CSF, decitabine, and busulfan-cyclophosphamide group and the busulfan-cyclophosphamide group were infections (34 [34%] and 32 [32%]), acute graft-versus-host disease (30 [30%] and 30 [30%]), and gastrointestinal toxicity (28 [28%] and 29 [29%]). 11 (11%) patients in the G-CSF, decitabine, and busulfan-cyclophosphamide group and 13 (13%) in the busulfan-cyclophosphamide group died of adverse events. There were no treatment related deaths. INTERPRETATION: Our results suggest that G-CSF, decitabine, and busulfan-cyclophosphamide conditioning is a better choice than busulfan-cyclophosphamide conditioning for patients with myelodysplastic syndrome-RAEB or secondary acute myeloid leukaemia evolving from myelodysplastic syndrome undergoing allogeneic HSCT. This conditioning could be a suitable therapuetic option for this patient population. FUNDING: None. TRANSLATION: For the Chinese translation of the abstract see Supplementary Materials section.


Subject(s)
Anemia, Refractory, with Excess of Blasts , Hematopoietic Stem Cell Transplantation , Leukemia, Myeloid, Acute , Myelodysplastic Syndromes , Humans , Male , Female , Busulfan/therapeutic use , Decitabine/therapeutic use , Anemia, Refractory, with Excess of Blasts/drug therapy , Anemia, Refractory, with Excess of Blasts/etiology , Cyclophosphamide/therapeutic use , Leukemia, Myeloid, Acute/drug therapy , Hematopoietic Stem Cell Transplantation/adverse effects , Myelodysplastic Syndromes/drug therapy , Transplantation Conditioning/methods , Chronic Disease , Granulocyte Colony-Stimulating Factor , Recurrence
2.
Blood Cells Mol Dis ; 77: 88-94, 2019 07.
Article in English | MEDLINE | ID: mdl-31005752

ABSTRACT

Decitabine and low-dose chemotherapy are common treatments for intermediate and high risk myelodysplastic syndromes (MDS). In this study, we retrospectively assessed the efficacy and toxicity of the two regimens for MDS-refractory anemia with excess blasts (MDS-RAEB) patients. A total of 112 patients with a diagnosis of MDS-RAEB are included. The overall response (OR) and complete remission (CR) rate was comparable between the two groups (OR: 64.1% vs. 66.7%, p = 0.60; CR: 23.4% vs. 31.3%, p = 0.64). The OR rates of 20 mg/m2/day and 15 mg/m2/day decitabine regimen were comparable (69.0% vs. 60.0%, p = 0.46). Overall survival (OS) did not differ significantly between the groups (20.7 vs. 13.5 months, p = 0.17). In a subgroup analysis that included only patients at ≥60 years of age, survival benefit of decitabine was apparent (20.6 vs. 10.0 months, p = 0.03). In hematological toxicities, the lowest count of platelet in the decitabine group was higher significantly. And, the incidence of Grade 3-4 infection in the decitabine group was lower significantly. Our results demonstrate that both decitabine and low-dose chemotherapy are effective for MDS-RAEB, but decitabine was safer. Decitabine might be a better choice for patients at ≥60 years of age.


Subject(s)
Anemia, Refractory, with Excess of Blasts/drug therapy , Anemia, Refractory, with Excess of Blasts/mortality , Antimetabolites, Antineoplastic/therapeutic use , Decitabine/therapeutic use , Adult , Aged , Anemia, Refractory, with Excess of Blasts/diagnosis , Anemia, Refractory, with Excess of Blasts/etiology , Antimetabolites, Antineoplastic/administration & dosage , Antimetabolites, Antineoplastic/adverse effects , Biomarkers , Decitabine/administration & dosage , Decitabine/adverse effects , Female , Genetic Testing , Humans , Kaplan-Meier Estimate , Male , Middle Aged , Myelodysplastic Syndromes/diagnosis , Myelodysplastic Syndromes/drug therapy , Myelodysplastic Syndromes/etiology , Myelodysplastic Syndromes/mortality , Odds Ratio , Prognosis , Treatment Outcome
3.
W V Med J ; 111(6): 34-6, 2015.
Article in English | MEDLINE | ID: mdl-26665895

ABSTRACT

Myeloid sarcoma is an extramedullary tumor consisting of immature hematopoietic cells of granulocytic or monocytic differentiation. While rare, it can be seen in a variety of clinical settings and is most commonly associated with acute myeloid leukemia (AML), myelodysplastic syndromes (MDS) and myeloproliferative neoplasms (MPN). We present a rare case of myeloid sarcoma occurring in the bladder of a 56 year old male. Myeloid sarcoma may be difficult to recognize due to its rarity and clinical and morphologic similarity to many other conditions; however, swift diagnosis is necessary as it is considered equivalent to AML. Prognostic indicators for myeloid sarcoma have not been well established, but survival may be improved by undergoing chemotherapy designed to treat AML.


Subject(s)
Anemia, Refractory, with Excess of Blasts/diagnosis , Sarcoma, Myeloid/pathology , Urinary Bladder Neoplasms/diagnosis , Anemia, Refractory, with Excess of Blasts/etiology , Humans , Male , Middle Aged , Prognosis , Sarcoma, Myeloid/diagnosis , Urinary Bladder Neoplasms/pathology
4.
Exp Hematol ; 39(12): 1119-23, 2011 Dec.
Article in English | MEDLINE | ID: mdl-21911093

ABSTRACT

Myelodysplastic syndrome (MDS) is known to be associated with functional abnormalities of B cells, including hypergammaglobulinemia and monoclonal gammopathy (MG). However, the pathogenesis of these immunological disorders has not been clarified. We report a patient who developed donor-derived MDS followed by leukemic transformation after cord blood transplantation for MDS with MG. Interestingly, MG reappeared before development of donor-derived MDS. We analyzed the immunoglobulin allotype gene polymorphisms to determine whether the MG after cord blood transplantation was of recipient origin or donor origin. Results of genetic analysis and enzyme-linked immunosorbent assay of IgG1 allotype revealed that the MG after cord blood transplantation was of donor origin. Although the mechanism of donor-derived MG remains unclear, the persistent presence of recipient's antigen presenting cells might have induced the abnormal immunoglobulin production.


Subject(s)
Anemia, Refractory, with Excess of Blasts/etiology , Cord Blood Stem Cell Transplantation/adverse effects , Living Donors , Paraproteinemias/surgery , B-Lymphocytes/pathology , DNA, Neoplasm/analysis , Fatal Outcome , Female , Humans , Immunoglobulin Allotypes/genetics , Immunoglobulin kappa-Chains , Infant, Newborn , Isoantibodies/immunology , Leukemia, Myeloid/etiology , Male , Middle Aged , Paraproteinemias/complications , Recurrence , Reoperation , T-Lymphocytes/pathology , Transplantation Conditioning , Transplantation, Homologous/adverse effects
5.
Adv Ther ; 28 Suppl 2: 10-5, 2011 Mar.
Article in English | MEDLINE | ID: mdl-21431505

ABSTRACT

The management of myelodysplastic syndromes (MDS) in elderly patients is a significant clinical problem. The therapeutic options range from observation alone for patients with low-risk disease, lenalidomide for patients with 5q-syndrome, to 5-azacytidine (5-AZA) for patients with higher risk of disease. In this paper, we summarize the clinical course of three patients with high-risk MDS treated with 5-AZA as well as the management and supportive care measures for adverse events. As expected, based on available clinical trials data, the agent resulted in clinical and hematological improvement in these patients with acceptable side effects. 5-AZA is an attractive option for elderly patients with high-risk MDS.


Subject(s)
Anemia, Refractory, with Excess of Blasts , Azacitidine , Bone Marrow , Life Expectancy , Myelodysplastic Syndromes , Pancytopenia , Age Factors , Aged , Anemia, Refractory, with Excess of Blasts/etiology , Anemia, Refractory, with Excess of Blasts/metabolism , Anemia, Refractory, with Excess of Blasts/physiopathology , Anemia, Refractory, with Excess of Blasts/therapy , Antimetabolites, Antineoplastic/administration & dosage , Antimetabolites, Antineoplastic/adverse effects , Azacitidine/administration & dosage , Azacitidine/adverse effects , Blood Component Transfusion , Bone Marrow/pathology , Bone Marrow/physiopathology , Bone Marrow Examination , Humans , Male , Monitoring, Physiologic , Myelodysplastic Syndromes/complications , Myelodysplastic Syndromes/metabolism , Myelodysplastic Syndromes/pathology , Myelodysplastic Syndromes/physiopathology , Myelodysplastic Syndromes/therapy , Pancytopenia/complications , Pancytopenia/metabolism , Pancytopenia/physiopathology , Pancytopenia/therapy , Treatment Outcome
6.
Am J Hematol ; 86(2): 163-9, 2011 Feb.
Article in English | MEDLINE | ID: mdl-21264898

ABSTRACT

Risk factors of mydelodysplastic syndromes (MDS) remain largely unknown. We conducted a hospital-based case-control study consisting of 403 newly diagnosed MDS patients according to World Health Organization classification and 806 individually gender and age-matched patient controls from 27 major hospitals in Shanghai, China, to examine relation of lifestyle, environmental, and occupational factors to risk of MDS. The study showed that all MDS (all subtypes combined) risk factors included anti tuberculosis drugs [odds ratio (OR)(adj) = 3.15; 95% confidence interval (CI) = 1.22-8.12] as an independent risk factor, benzene (OR(adj) = 3.73; 95% CI = 1.32-10.51), hair dye use (OR = 1.46; 95% CI = 1.03-2.07), new building and renovations (OR = 1.69; 95% CI = 1.11-2.00), pesticides (OR = 2.16; 95% CI = 1.22-3.82), and herbicides (OR = 5.33; 95% CI = 1.41-20.10) as relative risk factors. Risk factors of MDS subtype refractory cytopenia with multiple dysplasia (RCMD) were benzene (OR(adj) = 5.99; 95% CI = 1.19-30.16) and gasoline (OR(adj) = 11.44; 95% CI = 1.31-100.03) as independent risk factors, and traditional Chinese medicines (OR = 2.17; 95% CI = 1.15-4.07), pesticides (OR = 2.92; 95% CI = 1.37-6.25), and herbicides (OR = 12.00; 95% CI = 1.44-99.67) as relative risk factors. Smoking tobacco was significantly associated with refractory anemia with excess of blasts (RAEB) (OR(adj) = 2.43; 95% CI = 1.02-5.77). Education is shown as an independent protective factor against all MDS (OR(adj) = 0.90; 95% CI = 0.83-0.99) and RCMD (OR(adj) = 0.89; 95% CI = 0.79-0.99). These findings suggest that multiple modifiable behavioral, environmental, and occupational factors play a role in MDS etiology, and various MDS subtypes may have different susceptibility.


Subject(s)
Myelodysplastic Syndromes/classification , Myelodysplastic Syndromes/epidemiology , Adult , Aged , Aged, 80 and over , Anemia, Refractory, with Excess of Blasts/epidemiology , Anemia, Refractory, with Excess of Blasts/etiology , Antitubercular Agents/adverse effects , Case-Control Studies , China/epidemiology , Drugs, Chinese Herbal/adverse effects , Educational Status , Female , Hair Dyes/toxicity , Humans , Male , Middle Aged , Occupational Exposure/adverse effects , Pancytopenia/epidemiology , Pancytopenia/etiology , Risk Factors , Smoking/adverse effects , World Health Organization , Young Adult
7.
Rev Neurol (Paris) ; 166(8-9): 734-6, 2010.
Article in French | MEDLINE | ID: mdl-20472260

ABSTRACT

INTRODUCTION: Neurological involvement associated with copper deficiency has been reported recently in humans and may be under-recognized. CASE REPORT: A 65-year-old patient, with past history of gastrectomy 40 years earlier, developed a myelodysplastic syndrome and then subacute onset of progressive gait ataxia and paresthesias in the lower extremities. Serum vitamin B12 level was low but neurological deterioration persisted, despite vitamin replacement therapy and normal cobalamin level. Further diagnostic investigations revealed severe copper deficiency. Copper supplementation led to hematologic improvement and neurological stabilization. CONCLUSION: Copper and vitamin B12 deficiency, due to malabsorption as a cause of progressive neuromyelopathy and hematologic manifestations, may coexist.


Subject(s)
Anemia, Refractory, with Excess of Blasts/etiology , Ataxia/etiology , Copper/deficiency , Malabsorption Syndromes/etiology , Postgastrectomy Syndromes/complications , Aged , Copper/pharmacokinetics , Copper/therapeutic use , Humans , Male , Somatosensory Disorders/etiology , Vitamin B 12 Deficiency/diagnosis , Vitamin B 12 Deficiency/etiology , Vitamin B Complex/therapeutic use
10.
Gan To Kagaku Ryoho ; 33(6): 833-6, 2006 Jun.
Article in English | MEDLINE | ID: mdl-16770108

ABSTRACT

A 72-year-old female developed pancytopenia 4 years after breast cancer surgery. She had received regional radiation postoperatively, and tamoxifen for 4 years. Bone marrow examination demonstrated immature myeloblasts and dysplastic cells. Myelodysplastic syndrome (MDS) of refractory anemia with excess blasts (RAEB) was diagnosed, and the patient died of cerebral hemorrhage 4 months after the diagnosis of RAEB. Radiation and the administration of tamoxifen were suspected to have played a role in the development of secondary MDS.


Subject(s)
Anemia, Refractory, with Excess of Blasts/etiology , Antineoplastic Agents, Hormonal/adverse effects , Breast Neoplasms/drug therapy , Breast Neoplasms/radiotherapy , Carcinoma, Ductal, Breast/drug therapy , Carcinoma, Ductal, Breast/radiotherapy , Radiotherapy/adverse effects , Tamoxifen/adverse effects , Aged , Breast Neoplasms/surgery , Carcinoma, Ductal, Breast/surgery , Cerebral Hemorrhage/etiology , Female , Humans , Mastectomy
12.
Eur J Haematol ; 73(2): 128-33, 2004 Aug.
Article in English | MEDLINE | ID: mdl-15245512

ABSTRACT

Myelodysplastic syndrome (MDS) is frequently associated with autoimmune diseases such as polymyalgia, arthritis, and rarely, with systemic vasculitis. The pathogenesis of these autoimmune complications remains unknown, but there is increasing evidence of profound immune dysregulation in MDS. In the few cases reported so far, vasculitides associated with MDS affected mainly cutaneous vessels. Here we describe two cases of acute large-vessel vasculitis in association with MDS. The first patient is a 67-yr-old male presenting with a massive large-vessel arteritis as primary manifestation of refractory anemia with excess of blasts type 1 (RAEB-1). The second patient is a 60-yr-old male, who presented with acute thoracic aortitis after a 2-yr history of refractory anemia with ringed sideroblasts (RARS). Both patients received immunosuppressive treatment with steroids, leading to rapid improvement of systemic inflammatory symptoms, vessel wall injury and peripheral blood counts. Whereas the first patient displayed sustained favorable hematologic responses under long-term steroid therapy, there was a rapid transformation into secondary acute myeloid leukemia in the second patient. We conclude that large-vessel vasculitis should be added to the list of potential autoimmune complications in MDS. In this clinical setting, steroid therapy may alleviate inflammatory symptoms and result in beneficial hematologic responses.


Subject(s)
Arteritis/etiology , Myelodysplastic Syndromes/complications , Aged , Anemia, Refractory, with Excess of Blasts/etiology , Arteritis/drug therapy , Carotid Arteries/pathology , Humans , Leukemia, Myeloid , Male , Middle Aged , Splenic Artery/pathology , Steroids/therapeutic use , Treatment Outcome
13.
Tunis Med ; 81(4): 226-9, 2003 Apr.
Article in French | MEDLINE | ID: mdl-12848003

ABSTRACT

Between 1989 and 1999, 36 cases with primary myelodysplastic syndromes were diagnosed. They were 15 male and 21 females, the median age was 62 years (range: 22 to 90 years). Eighty one per cent of patients were presented symptoms of anemia. Lymphadenopathy, splenomegaly and skin manifestations were noted in 25% of cases. Hemogram showed anemia, leucopenia and thrombocytopenia respectively in 97%, 44% and 55% of cases. Refractory anemia with excess blasts (AREB) is the most frequent FAB subtypes of MDS (17 cases). Cytogenetic study concerned 24 patients. In 13 cases the karyotype was pathological with deletion 5 q in 64% of cases. Seventeen patients have received a chemotherapy. Survival rate to 36 months is 11%. At the time, the only curative treatment is the bone marrow transplantation, which is proposed to young patients with HLA identical donor.


Subject(s)
Anemia, Refractory, with Excess of Blasts/etiology , Myelodysplastic Syndromes/diagnosis , Adult , Aged , Aged, 80 and over , Female , Humans , Leukopenia/etiology , Lymphatic Diseases/etiology , Male , Middle Aged , Myelodysplastic Syndromes/drug therapy , Myelodysplastic Syndromes/genetics , Skin Diseases/etiology , Splenomegaly/etiology , Thrombocytopenia/etiology
14.
Int J Hematol ; 75(1): 67-71, 2002 Jan.
Article in English | MEDLINE | ID: mdl-11843294

ABSTRACT

We report a case of therapy-related myelodysplastic syndrome (t-MDS) in adult T-cell lymphoma. A 69-year-old man suffered from cutaneous adult T-cell lymphoma, which was treated with radiation to the skin and combination chemotherapy of CHOP-V-MMV and VEPA-B. After 14 months of these therapies, anemia and thrombocytopenia appeared, and bone marrow aspiration smears showed immature myeloblasts, dysplastic erythroblasts, and micromegakaryocytes. Therapy-related MDS of refractory anemia with an excess of blasts was diagnosed. Cytogenetic study of the bone marrow cells showed 5q- and additional abnormalities. Rearrangement of the MLL gene was observed in the bone marrow cells. Mutations of N-ras codons at 12,13, and 61, p53 tumor suppressor gene, and monoclonal integration of human T-lymphotrophic virus -1 provirus DNA were not observed in the bone marrow cells. The patient died of pneumonia 21 months after diagnosis of cutaneous adult T-cell lymphoma.


Subject(s)
Anemia, Refractory, with Excess of Blasts/etiology , Antineoplastic Combined Chemotherapy Protocols/adverse effects , Lymphoma, T-Cell, Cutaneous/complications , Radiotherapy/adverse effects , Acute Disease , Aged , Anemia, Refractory, with Excess of Blasts/genetics , Anemia, Refractory, with Excess of Blasts/virology , Antineoplastic Combined Chemotherapy Protocols/administration & dosage , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Bleomycin/administration & dosage , Bleomycin/adverse effects , Chromosome Aberrations , Combined Modality Therapy , Cyclophosphamide/administration & dosage , Cyclophosphamide/adverse effects , Disease Progression , Doxorubicin/administration & dosage , Doxorubicin/adverse effects , Doxorubicin/analogs & derivatives , Etoposide/administration & dosage , Etoposide/adverse effects , Fatal Outcome , HTLV-I Infections/complications , Human T-lymphotropic virus 1/isolation & purification , Humans , Japan , Leukemia, Myeloid/complications , Leukemia-Lymphoma, Adult T-Cell/complications , Lymphoma, T-Cell, Cutaneous/drug therapy , Lymphoma, T-Cell, Cutaneous/radiotherapy , Lymphoma, T-Cell, Cutaneous/virology , Male , Nitrosourea Compounds/administration & dosage , Nitrosourea Compounds/adverse effects , Prednisolone/administration & dosage , Prednisolone/adverse effects , Proviruses/isolation & purification , Remission Induction , Translocation, Genetic , Vincristine/administration & dosage , Vincristine/adverse effects
16.
Leukemia ; 14(7): 1314-5, 2000 Jul.
Article in English | MEDLINE | ID: mdl-10914558
17.
Leuk Res ; 23(4): 323-30, 1999 Apr.
Article in English | MEDLINE | ID: mdl-10229317

ABSTRACT

The skin involvement of the myelodysplastic syndrome (MDS) can take the form of either a neoplastic infiltration or various non specific lesions. The occurrence of these lesions may be the presenting feature of the disease (MDS) or may herald its progression to acute leukemia. Recognition and early diagnosis have therapeutic and prognostic significance.


Subject(s)
Myelodysplastic Syndromes/pathology , Skin/pathology , Adolescent , Aged , Aged, 80 and over , Anemia, Refractory, with Excess of Blasts/etiology , Anemia, Refractory, with Excess of Blasts/pathology , Female , Humans , Leukemia, Myelomonocytic, Chronic/pathology , Leukemic Infiltration/pathology , Male , Middle Aged , Myelodysplastic Syndromes/complications , Pyoderma Gangrenosum/etiology , Pyoderma Gangrenosum/pathology , Sweet Syndrome/etiology , Sweet Syndrome/pathology
18.
J Trop Pediatr ; 45(2): 112-5, 1999 04.
Article in English | MEDLINE | ID: mdl-10341509

ABSTRACT

Thirty-two children with extramedullary myeloid cell tumour (EMT) who constituted 41 per cent of children with acute myeloid leukaemia (AML) were studied to ascertain their laboratory characteristics and potential problems in diagnosis. The diagnosis, established by peripheral blood smear and/or bone marrow examination, was AML (n = 29) and refractory anaemia with excess blasts in transformation (RAEB-t; n = 3). The six referred patients in whom the diagnosis had been missed, and two cases wrongly reported as histiocytosis on aspiration cytology, were those in whom a peripheral blood smear had not been examined. It is concluded that diagnostic work-up of proptosis must include a full haemogram, meticulous peripheral blood smear examination, repeated if necessary, and bone marrow examination where relevant. RAEB-t cases with extramedullary myeloid cell tumour should be classified as acute myeloid leukaemia.


Subject(s)
Leukemia, Myeloid/diagnosis , Orbital Neoplasms/diagnosis , Acute Disease , Anemia, Refractory, with Excess of Blasts/diagnosis , Anemia, Refractory, with Excess of Blasts/etiology , Child , Child, Preschool , Exophthalmos/etiology , Female , Humans , India , Infant , Leukemia, Myeloid/complications , Male , Orbital Neoplasms/complications
19.
Leuk Res ; 23(2): 167-76, 1999 Feb.
Article in English | MEDLINE | ID: mdl-10071132

ABSTRACT

Fitness landscapes, which provide a unique perspective for viewing co-evolving cell populations, were used to study the evolution of CML and MDS. This led to several conclusions: (1) accelerated phase CML and RAEB/RAEBt are not specific disease entities. They represent the time when AML cells are replacing preleukemia cells; (2) monoclonal hemopoiesis and RA/RARS represent a variety of clinical syndromes with a common appearance but with different evolutionary potential; (3) malignant cells alter the fitness landscape enhancing their proliferative advantage. These studies provide the basis for new approaches to treatment.


Subject(s)
Anemia, Refractory, with Excess of Blasts/etiology , Leukemia, Myelogenous, Chronic, BCR-ABL Positive/etiology , Anemia, Refractory, with Excess of Blasts/pathology , Anemia, Refractory, with Excess of Blasts/therapy , Animals , Biological Evolution , Hematopoiesis , Humans , Leukemia, Myelogenous, Chronic, BCR-ABL Positive/pathology , Leukemia, Myelogenous, Chronic, BCR-ABL Positive/therapy
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