ABSTRACT
By retrospective analysis of 88 patients from the British Society of Blood and Marrow Transplantation registry, we investigated the effect of in vivo T-cell depletion in HLA-identical sibling reduced-intensity conditioning (RIC) allografts for adult AML by comparing patients who received alemtuzumab with those without alemtuzumab conditioning. Both groups were equivalent for age, sex, karyotype and disease status at transplant. With a median follow-up of 27 months (3-72 months) and 48 months (7-72 months), the 2- and 5-year overall survival, with or without alemtuzumab, is 60 and 60% (P=0.80) and 61 and 53%, respectively (P=0.85). The 2-year non-relapse mortality is 12% with alemtuzumab, and 17% without alemtuzumab (P=0.49). The 2-year relapse rate is 35% with alemtuzumab compared with 19% without alemtuzumab (P=0.28). Grades II-IV acute GVHD occurred in 22% (8/37) without alemtuzumab compared with 14% (7/51) given alemtuzumab (P=0.25). Extensive chronic GVHD occurred in 47% (14/30) not given alemtuzumab compared with 4% (2/45) who were given alemtuzumab (P=0.001). Among evaluable patients, the risk of infections was higher in those treated with alemtuzumab compared with those not treated with alemtuzumab (79 vs 57%, respectively, P=0.02). In conclusion, alemtuzumab has a beneficial effect by reducing chronic GVHD without affecting overall survival. Further studies are warranted before alemtuzumab can be recommended as standard in RIC allografts for AML.
Subject(s)
Antibodies, Monoclonal/therapeutic use , Antibodies, Neoplasm/therapeutic use , Graft vs Host Disease/drug therapy , Hematopoietic Stem Cell Transplantation/methods , Leukemia, Myeloid, Acute/therapy , Transplantation Conditioning/methods , Adolescent , Adult , Aged , Alemtuzumab , Antibodies, Monoclonal, Humanized , Antineoplastic Agents/therapeutic use , Chronic Disease , Drug Evaluation , Female , Hematopoietic Stem Cell Transplantation/adverse effects , Hematopoietic Stem Cell Transplantation/mortality , Humans , In Vitro Techniques , Leukemia, Myeloid, Acute/complications , Leukemia, Myeloid, Acute/mortality , Lymphocyte Depletion/methods , Middle Aged , Registries , Retrospective Studies , Siblings , Survival Rate , Transplantation Conditioning/mortality , Transplantation, Homologous , Young AdultABSTRACT
In myeloma, the prognostic impact of different strategies used to detect chromosome 13 deletion (Delta13) remains controversial. To address this, we compared conventional cytogenetics and interphase fluorescence in situ hybridization (iFISH) in a large multicenter study (n=794). The ability to obtain abnormal metaphases was associated with a poor prognosis, which was worse if Delta13, p53 deletion or t(4;14) was present, but only Delta13 remained significant on multivariate analysis. Patients with Delta13, by either cytogenetics or iFISH, had a poor prognosis. However, when cases with Delta13 detectable by both cytogenetics and iFISH were separated from those detected by iFISH only, the poor prognosis of iFISH-detectable Delta13 disappeared; their outcome matched that of patients with no detectable Delta13 (P=0.115). Addition of ploidy status to iFISH-Delta13 did not affect the prognostic value of the test. Indeed both cytogenetics and iFISH Delta13 divided both hyperdiploidy and nonhyperdiploidy into two groups with similar prognoses, indicating that the poor prognosis of ploidy is entirely due to its association with Delta13. We conclude that Delta13 detected by metaphase analysis is a critical prognostic factor in myeloma. Absence of Delta13, even in those patients yielding only normal or no metaphases, is associated with a relatively good prognosis.
Subject(s)
Chromosome Deletion , Chromosomes, Human, Pair 13 , Multiple Myeloma/genetics , Multiple Myeloma/pathology , Adult , Aged , Aged, 80 and over , Cohort Studies , Female , Genes, Immunoglobulin Heavy Chain , Genes, p53 , Humans , In Situ Hybridization, Fluorescence , Male , Middle Aged , Ploidies , Prognosis , Survival Analysis , Translocation, GeneticSubject(s)
Transplantation Conditioning/methods , Antineoplastic Agents/administration & dosage , Hematologic Neoplasms/therapy , Hematopoietic Stem Cell Transplantation/adverse effects , Hematopoietic Stem Cell Transplantation/methods , Hematopoietic Stem Cell Transplantation/standards , Humans , Radioimmunotherapy/methods , Transplantation Conditioning/standardsABSTRACT
The erythroid transcription factor erythroid factor-1 (EF1) plays a critical role in the transcription of erythroid-specific genes. Here we report the presence of a factor with the mobility and sequence-specific DNA-binding characteristics of EF1 at low abundance in a wide variety of non-erythroid cell types. This is the first report of an EF1-like activity in non-erythroid cells and indicates that this factor may play a role in the regulation of genes expressed in such cells.
Subject(s)
DNA-Binding Proteins/analysis , Transcription Factors/analysis , Animals , Binding, Competitive , Cell Line , Cell Nucleus/analysis , DNA/metabolism , Electrophoresis, Polyacrylamide Gel , Erythroid-Specific DNA-Binding Factors , HeLa Cells , Humans , Leukemia, Erythroblastic, Acute , Mice , T-Lymphocytes/analysis , Teratoma/analysis , Tumor Cells, CulturedABSTRACT
We used a standard methyl cellulose method to assay erythroid progenitor cells in the blood of 35 patients with untreated CGL and of 18 normal controls. In 28 patients we simultaneously assayed granulocyte/monocyte committed progenitor cells (CFU-c) by an agar method. Circulating erythroid burst-forming units (BFU-e) in CGL were increased above normal by a factor of about 180; CFU-c were increased by a factor of about 9000. Both BFU-e and CFU-c numbers were linearly related to the total leucocyte count in individual patients but not to numbers of circulating blast cells. There was a positive correlation in individual patients between CFU-c and BFU-e numbers. Circulating BFU-e and erythroid colony-forming cells (CFU-e) were unable to proliferate in vitro in the absence of erythropoietin. We conclude that erythroid progenitor cells are involved in the 'clonal expansion' that characterizes CGL, but apparently to a lesser extent than are granulocyte/moonocyte progenitor cells.
