Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0023473 (chronic myeloid leukemia)
 18,916 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The aim of the present study was to assess the influence of socioeconomic status (SeS) on the outcome of allo-SCT at a Brazilian SCT center. In total, 201 patients receiving HLA-identical related allo-SCTs were studied. The median age was 30 years. Overall, 163 patients had malignancies (CML 68, ALL/AML 63, myelodysplastic syndrome 12 and others 20). SeS was defined according to the Brazilian Association of Market Research Agencies classification, where people are clustered in groups A-E (richest to poorest). In total, 146 patients (72%) were classified as richest (A+B+C) and 55 (28%) as poorest (D+E). The D+E SeS group was associated with a higher incidence of chronic GVHD and acute GVHD (hazard ratio (HR)=2.61; P=0.001 and HR=2.62; P=0.001, respectively), better platelet and neutrophil engraftment (HR=1.94; P=<0.001 and HR=2.12; P=0.001) and with a higher TRM in multivariate analysis (HR=1.92; P=0.039). Estimated overall survival at 5 years was 55.2%. A D+E SeS (HR=2.13; P=0.001) was associated with a worse survival on multivariate analysis. In conclusion, a lower SeS is a strong prognostic factor in patients undergoing allo-SCT in Brazil, influencing engraftment, TRM and overall survival.
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PMID:Patient socioeconomic status as a prognostic factor for allo-SCT. 1897 20

Do some patients benefit from an unrelated donor (URD) transplant because of a stronger graft-versus-leukemia (GVL) effect? We analyzed 4099 patients with acute myeloid leukemia (AML), acute lymphoblastic leukemia (ALL), and chronic myeloid leukemia (CML) undergoing a myeloablative allogeneic hematopoietic cell transplantation (HCT) from an URD (8/8 human leukocyte antigen [HLA]-matched, n=941) or HLA-identical sibling donor (n=3158) between 1995 and 2004 reported to the CIBMTR. In the Cox regression model, acute and chronic GVHD were added as time-dependent variables. In multivariate analysis, URD transplant recipients had a higher risk for transplantation-related mortality (TRM; relative risk [RR], 2.76; P< .001) and relapse (RR, 1.50; P< .002) in patients with AML, but not ALL or CML. Chronic GVHD was associated with a lower relapse risk in all diagnoses. Leukemia-free survival (LFS) was decreased in patients with AML without acute GVHD receiving a URD transplant (RR, 2.02; P< .001) but was comparable to those receiving HLA-identical sibling transplants in patients with ALL and CML. In patients without GVHD, multivariate analysis showed similar risk of relapse but decreased LFS for URD transplants for all 3 diagnoses. In conclusion, risk of relapse was the same (ALL, CML) or worse (AML) in URD transplant recipients compared with HLA-identical sibling transplant recipients, suggesting a similar GVL effect.
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PMID:The graft-versus-leukemia effect using matched unrelated donors is not superior to HLA-identical siblings for hematopoietic stem cell transplantation. 1905 78

A higher absolute lymphocyte count 1 month (LC30) after allogeneic hematopoietic stem cell transplantation (HSCT) is associated with better outcome in patients transplanted from a matched sibling. We studied 102 SCT patients with unrelated donor and matched unrelated donors and the relationship between LC30 and outcome in patients with myelogenous leukemia. Conditioning was myeloablative using cyclophosphamide (Cy) with busulfan (Bu; n=61) or total body irradiation (TBI; n=41). LC30 was low (<0.2x10(9)/L) in 18 patients, intermediate (0.2-1.0x10(9)L) in 67, and high (>1.0x10(9)/L) in 17 patients. In multivariate analysis, independent factors associated with high relapse-free survival (RFS) were high LC30, high CD34 cell-dose, and absence of acute graft-versus-host disease (aGVHD) grades II-IV. When analyzed as a continuous variable in multivariate analysis, a higher LC30 was associated with a lower transplant-related mortality (TRM; relative hazard [RH]=0.87, P < .05), higher relapse-free survival (RH=3.42, P=.036), and improved survival (RH=4.53, P=.016, excluding GVHD). In patients with high, intermediate, and low LC30, overall survival (OS) was 91% versus 60%, versus 36% (P=.02 and .001, respectively). This significant relationship was maintained in patients who did not develop GVHD by day 30. Significant risk factors to develop low LC30 was chronic myelogenous leukemia (CML; hazard ratio [HR] 0.73, P=.001), prophylaxis with granulocyte colony-stimulating factor (G-CSF; HR 0.81, P=.02) and aGVHD (HR 0.84, P=.05). These results indicate that LC30 is an independent prognostic factor for transplant outcome in matched unrelated SCT for myelogenous malignancies.
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PMID:Lymphocyte recovery is a major determinant of outcome after matched unrelated myeloablative transplantation for myelogenous malignancies. 1966 Jul 24

We retrospectively compared clinical outcomes in 1593 T-replete unrelated donor (URD) marrow transplant recipients with AML, MDS and CML who received myeloablative conditioning regimens of either BU and CY (BuCy), standard-dose Cy/TBI (1000-1260 cGy) or high-dose Cy/TBI (1320-1500 cGy). Subjects were drawn from patients transplanted between 1991 and 1999 facilitated by the National Marrow Donor Program. Patients who received high-dose Cy/TBI regimens were slightly younger, more likely to receive a mismatched transplant and to have intermediate or advanced disease compared with patients in the BuCy or standard-dose TBI group. Neutrophil recovery was significantly higher in the standard-dose CY/TBI group compared with the high-dose Cy/TBI or BuCy group. Patients who received the high-dose Cy/TBI regimen had an increased risk of developing grades III-IV aGVHD when compared with the control group who received BuCy (P = 0.011). OS, disease-free survival (DFS), TRM and relapse were not significantly different between any of the regimens. We conclude that BuCy, standard-dose and high-dose Cy/TBI regimens have equivalent efficacy profiles for OS, DFS, TRM and relapse risk in patients undergoing T-replete URD marrow transplantation for AML, CML and MDS.
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PMID:Comparative analysis of BU and CY versus CY and TBI in full intensity unrelated marrow donor transplantation for AML, CML and myelodysplasia. 2040 Sep 89

Allogeneic hematopoietic SCT is an effective treatment in accelerated (AP) or blast phase (BP) CML. Imatinib (IM) has transient but significant activity in advanced phases of CML, which may permit early allografting for responding patients. To identify prognostic factors in allograft recipients previously treated with IM, we analyzed 449 allogeneic hematopoietic SCTs performed from 1999 to 2004 in advanced-phase CML, using the data reported to the Center for International Blood and Marrow Transplant Research. CML patients in second chronic phase (CP2, n=184), AP (n=185) and BP (n=80) received HLA-identical sibling (27%), related (3%), or matched or mismatched unrelated donor (70%), peripheral blood (47%) or BM (53%) hematopoietic SCT after myeloablative (78%) or non-myeloablative (22%) conditioning. In all, 52% in CP2, 49% in AP and 46% in BP received IM before hematopoietic SCT. Disease-free survival was 35-40% for CP2, 26-27% for AP and 8-11% for BP. Cumulative incidence of acute and chronic GVHD and TRM were not affected by the stages of CML or pre-hematopoietic SCT IM exposure. Multivariate analyses showed that conventional prognostic indicators remain the strongest determinants of transplant outcomes. In conclusion, there are no new prognostic indicators of the outcomes of allogeneic hematopoietic SCT for advanced-phase CML in the IM era.
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PMID:Prognostic factors for outcomes in allogeneic transplantation for CML in the imatinib era: a CIBMTR analysis. 2198 36

It was previously shown that chronic myeloid leukemia (CML) patients transplanted with peripheral blood progenitor cells (PBPC) from HLA-C allele-matched donors had better clinical outcome when lacking the HLA-C-encoded KIR epitope C2. We investigated whether this holds true in other diseases and in HLA-C allele-mismatched patients. Twenty-four myelodysplastic syndrome (MDS), 39 acute myeloid leukemia (AML)/CML, and 34 acute lymphoblastic leukemia/non-Hodgkin lymphoma patients received unrelated unmanipulated PBPC. HLA matching was analyzed retrospectively (including DNA-based direct sequencing of HLA-C). Only in AML/CML, the C2 ligand was associated with impaired overall survival (OS, p < 0.05). We next calculated the impact of donor/recipient HLA-C allele matching within the C1 and C2 groups. Surprisingly, AML/CML and MDS patients with C2 ligands profited from HLA-C allele mismatching (OS, p < 0.01), whereas in the C1 group, allele matching was beneficial (p < 0.05). HLA-C allele mismatching in the C2 KIR ligand group was associated with lower TRM (OR 0.48, p < 0.009) and lower relapse rate (OR 2.7 p < 0.1) when compared to allele-matched C2 patients. Thus, patients could be assigned to a low- and a high-risk group according to their C1/C2 ligand status and the HLA-C allele matching degree. These data suggest that four-digit allele matching of HLA-C has differential effects dependent on the presence of C1 and C2 KIR epitopes in the patient.
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PMID:The impact of HLA-C matching depends on the C1/C2 KIR ligand status in unrelated hematopoietic stem cell transplantation. 2292 51


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