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)

Autologous bone marrow transplantation (ABMT) has developed considerably in the past 15 years and is now a routine procedure for the consolidation of acute leukemias, non-Hodgkin's lymphomas and Hodgkin's disease. In addition, ABMT has been tested in multiple myeloma (MM) and even considered in highly selected cases of chronic myelocytic leukemia (CML). Interest has resulted from the discovery of new purging procedures such as long-term cultures with or without serum-free media containing various lymphokines, the evaluation of cryoinjury on malignant cells, the increased detection of minimal residual disease using PCR, and the acceleration of hemopoietic recovery post-ABMT through the use of peripheral blood stem cells and/or lymphokines. Results presented include data from the international (ABMTR) and European (EBMT) registries, and our own unit in Paris. With respect to acute leukemias, (a) the EBMT listed 1,688 patients. The overall results were as follows: for patients autografted in complete remission (CR) 1, the leukemia-free survival and relapse rate at 7 years were 48 +/- 2% and 41 +/- 3% for AML and 44 +/- 5% and 45 +/- 5% in acute lymphoblastic leukemia (ALL), respectively. In CR2, the figures were 34 +/- 4% and 54 +/- 5% for AML and 32 +/- 3% and 62 +/- 4% for ALL, respectively. Patients not relapsing at 1 year post-ABMT had a probability of being cured at 7 years of 86 and 71% if autografted in CR1 and CR2 for AML and 81 and 59% for ALL, respectively. Multivariate analysis of relapse rates in several subpopulations confirmed the efficacy of marrow purging in AML CR1: in patients transplanted prior to January 1988 (minimum follow-up of 2 years), the relapse rate with purged marrow was 35 +/- 5% vs. 47 +/- 3% (p less than 0.005). (b) In Paris, St-Antoine, using TBI and marrow purged with mafosfamide at levels individually adjusted (Blood 1986;67:1367), the probability of remission and DFS were 84 and 62% in AML CR1 63 and 59% in ALL CR1, respectively. There was a statistically significant relationship between the relapse rate and the residual amount of CFUGM progenitors in the marrow after purging. The cutoff point was 0.3%, with a relapse rate of 54% in those receiving marrow containing the higher residual CFUGM fractions and only 29% in those receiving less. With respect to non-Hodgkin's lymphomas, the EBMT listed 698 patients. In intermediate or high grade lymphomas, the DFS at 6 years was 30% and 18% in sensitive and resistant relapses, respectively.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Autologous bone marrow transplantation in hematological malignancies. 204 65

Eighty consecutive patients were transplanted with human leukocyte antigen (HLA)-identical sibling marrow for acute myelogenous leukemia (AML, N = 29), acute lymphoid leukemia (ALL, N = 23), or chronic myelogenous leukemia (CML, N = 28). Donor marrow was depleted of lymphocytes using counterflow centrifugation. Median age of the recipients was 31 years. Pretransplant conditioning consisted of cyclophosphamide and fractionated total body irradiation (TBI). Graft failure occurred in 4 of 77 evaluable patients (5%). The probability of acute graft-versus-host disease (GVHD) > or = grade 2 at day 100 after transplantation was 15%. The projected 3-year estimate of extensive chronic GVHD was 12%. The projected 3-year probability of relapse was 30% in transplants for AML in first complete remission (CR1), 35% after transplantation for ALL in CR1, and 38% after transplantation for CML in first chronic phase (CP1). The projected 3-year probability of leukemia-free survival (LFS) was 56% after transplantation for AML-CR1, 42% in patients transplanted for ALL-CR1, and 49% after transplantation for CML-CP1. The chance of relapse was significantly reduced in a cohort of 72 standard risk patients conditioned with a regimen intensified by the addition of anthracyclines. This resulted in DFS at 4 years after BMT of 63% compared to 39% in a historical control group. Enrichment of the donor marrow with NK-cells did not increase the incidence of GVHD, but did neither decrease the relapse rate after BMT. In bone marrow transplantation for leukemia, counterflow centrifugation is a useful technique for the prevention of GVHD. Further efforts should be made to reduce relapse-rate, particularly in high risk patients.
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PMID:Allogeneic bone marrow transplantation for leukemia with marrow grafts treated by counterflow centrifugation. 812 52

Thirty-one patients with either advanced AML (18) or blastic CML (13) were treated with an intensive timed sequential combination of VP-16 (100 mg/m2/day i.v., days 1-3 and 8-10), intermediate-dose Ara-C (500 mg/m2 i.v. over 1 h q 12 h, days 1-3 and 8-10) and carboplatin (150 mg/m2/day i.v. continuous infusion, days 1-3 and 8-10). CR rates were 9/18 (50%) for patients with AML and 9/13 (69%) for those with blastic CML, for an overall CR rate of 58%. Among patients with AML, CR rates for specific subgroups were: primary resistant disease 2/6; resistant relapse 1/5; second relapse 6/7. Ten patients were refractory to VAC and three (10%) died of complications during marrow hypoplasia. Median overall survival was 7 months, and median DFS of the 18 responders 4 months. The major toxicity was myelosuppression and infection. The VAC regimen has significant activity and acceptable toxicity in myelogenous leukemias. The very high response rate observed in blastic CML warrants further testing of carboplatin-based regimens in this poor-risk form of leukemia.
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PMID:A phase II study of VP-16, intermediate-dose Ara-C and carboplatin (VAC) in advanced acute myelogenous leukemia and blastic chronic myelogenous leukemia. 865 69

In this pilot study; we assessed the immunosuppressive and the antileukemic potential of a combination of busulfan and melphalan prior to allogeneic BMT in 25 adult patients with refractory or relapsed hematological malignancies. Twelve patients were transplanted for acute myeloid leukemia (relapse: five patients; primary refractory: four patients; second remission: two patients), two patients for primary refractory acute lymphoblastic leukemia, nine patients for chronic myelogenous leukemia (accelerated phase: six patients; blastic phase: three patients) and two patients for primary refractory lymphoma. All received an unmanipulated marrow from HLA-identical siblings. All patients but one engrafted (median time to ANC > or = 0.5 x 10(9)/l = 17 days, to platelets > or = 50 x 10(9)/l = 29 days). Full chimerism was documented in the seven evaluable patients. The probability for developing acute GVHD was 58%. Complete remission was obtained in 17/18 measurable patients. With a 42 month median follow-up, eight patients are alive in unmaintained remission. The 4-year probabilities for relapse, survival, and DFS are respectively: 42%, 35%, and 31%. These results show that the combination of busulfan and melphalan ensures an effective immunosuppression allowing long-term engraftment. This regimen can provide long-term disease-free survival in patients with high-risk disease and thus represents an interesting alternative to the CY and/or TBI-containing regimens.
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PMID:A pilot study of busulfan and melphalan as preparatory regimen prior to allogeneic bone marrow transplantation in refractory or relapsed hematological malignancies. 887 8

Timing of transplantation in the chronic phase of chronic myeloid leukemia (CML) and previous treatment with interferon remains controversial. We have tried to discover what influence pretreatment with interferon alpha (IFN-A) has on the results of allogeneic bone marrow transplantation for CML patients treated in a single institution. Fifty-one consecutive patients with chronic phase Ph-positive CML who received an allogeneic bone marrow transplantation from a HLA-identical familial donor were evaluated. Thirty had been treated with IFN-A (IFN+ group) prior to BMT and twenty-one had not (IFN- group). Both groups were homogeneous for clinical characteristics such as age, sex, previous chemotherapy, disease status, and time from diagnosis to transplant. No difference was found in neutrophil and platelet count recovery between the IFN+ and IFN- group. The incidence of acute and chronic GVHD, VOD and severe mucositis was not significantly different. Relapse and both overall survival and DFS were similar for both groups. No adverse effects of prior IFN exposure on the outcome of HLA-identical sibling donor BMT for chronic phase CML patients were found in this study.
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PMID:Absence of influence of prior treatment with interferon on the outcome of allogeneic bone marrow transplantation for chronic myeloid leukemia. 967 95

Blood cell transplantation (BCT) is now common practice in the autologous setting. We performed a pilot study of allogeneic BCT, collected after the priming of an HLA-identical sibling with a glycosylated rhu-G-CSF (lenograstim) (10 microg/kg). Fifty-four patients were included (38 +/- 11; M/F = 33/21; CML (n = 17), AML (n = 14), ALL (n = 15); MDS (n = 8)). Transplant procedures were standard (TBI regimen = 47 (87%); MTX-CsA: n = 37; CsA-PDN: n = 17). No serious adverse events were reported in donors. A median of 11 (3.5-29.1) x 10(6)/kg CD34+ cells, 332 (33-820) x 10(6)/kg CD3+ cells were collected. Four patients did not engraft (early death: n = 2; graft failure: n = 2). Fifty-one patients initially recovered 0.5 x 10(9)/l ANC and 25 x 10(9)/l platelets at 15 (10-30) and 13 (9-188) days. 29/51 and 29/38 experienced grade > or =2 acute and chronic GVHD. With a median follow-up of 25 months (18-36), relapse rate is 16% +/- 8, survival and DFS probabilities are similar (50% +/- 13). A better outcome is documented for patients under 45 years and in the early phase of the disease (n = 28), with an identical survival and DFS of 71% +/- 13. In conclusion, lenograstim is a potent rhu-G-CSF for mobilisation of allogeneic hematopoietic progenitors. Two-year follow-up indicates good haematological recovery but some concerns about graft failure and chronic GVHD have arisen deserving prospective evaluation.
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PMID:Mobilisation of healthy donors with lenograstim and transplantation of HLA-genoidentical blood progenitors in 54 patients with hematological malignancies: a pilot study. 1045 58

Among 290 BMT procedures: 74 AML, 78 ALL, 34 CML, 6 SAA, 3 MDS, 42 HD, 35 NHL, 11 MM, and 7 solid tumours (breast or testis cancer) Allogeneic BMT was performed in 76 patients and ABMT/APBCT in 214 patients. Survival, DFS and relapse curves were calculated using the Kaplan-Meier product limit method. Variables potentially affecting survival and DFS were assessed in a multivariate analysis by the Cox proportional hazard model in a stepwise regression. The promising results were obtained in high risk adult ALL in the first CR. DFS in CR1 patients transplanted after full dose induction and high dose consolidation was significantly longer if compared to those who received dose/time reduced or postponed treatment. For CR> or =2 patients and with CNS involvement at diagnosis ABMT offers a salvage therapy that needs further improvement. In relapsed and refractory HD better results are obtained in patients relapsing > 1 year after first CR and in patients with entirely nodal localisation of this relapse. In NHL bone marrow and spleen infiltration at diagnosis appear to be an unfavourable prognostic factor.
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PMID:Allogeneic and autologous bone marrow transplantation in single centre experience. 991 50

The oral antitumor drugs against hematological malignancies are summarized. Sobuzoxane, a topoisomerase II inhibitor, is useful for the treatment of lymphoma, especially adult T cell leukemia/lymphoma. Sobuzoxane has an effect to protect against doxorubicin cardiotoxicity. Cytarabine ocfosfate, a derivative of cytosine arabinoside, is a useful agent against acute leukemia and MDS, especially RAEB, RAEB in T, CMMoL. The JALSG AML 92 study for APL with all-trans retinoic acid resulted in a 89% CR rate in 196 and 64% 4-year DFS in CR cases. Hydroxycarbamide is can control the WBC in CML. This agent is also effective for other myeloproliferative disorders, such as acute leukemia and MDS. Oral administration of 50 mg etoposide daily showed a good outcome in old patients with malignant lymphoma. For old patients and those with refractory hematological malignancies, oral administration of these agents can offer a new form of palliative therapy to allow them to remain at home while maintaining a high quality of life.
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PMID:[Oral antitumor drugs for hematological malignancies]. 1006 91

Peripheral blood stem cell transplants (PBSCT) from unrelated donors (n = 37) were compared with bone marrow transplants (BM, bone marrow group, n = 37) in a matched pair analysis. Ten patients (2, class 1) in the alloPBSCT group and seven patients (2, class 1) in the BM group had one HLA locus mismatch donor, respectively. The following factors were matched: HLA-compatibility, diagnosis, disease stage, age and gender. The median age in the PBSC group was 37 years (19-56, excluding one 6-year-old child) and in the BM group 37 years (18-53). The BM group consisted of 12 females and 25 males, 17 females and 20 males were in the PBSC group. Twelve patients in the BM and 11 patients in the PBSC group were diagnosed with AMI,; 7/7, ALL; 15/15, CML; 2/3, MDS; 1/1, NHL. Thirty-four (14/20) of the 74 patients (45%) were considered as high risk patients. The conditioning regimen was BU/CY for standard risk patients with myeloid diseases (31 patients) and TBI/CY for ALL and NHL patients (36 patients); six patients received intensified conditioning with VP16 (2 patients), thiotepa (2 patients) or melphalan (1 patient). The GVHD prophylaxis regimen was used according to the Seattle protocol. DFS was 51% (19 patients) with a median of 352 days and 59% (21 patients) with a median of 760 days, in PBSC and BM transplants, respectively. The median time to leukocyte engraftment in PBSC patients was 14 days (range 6-26 days) and in the BM group 19 days (range 9-29 days; P < 0.02). The time of platelet engraftment did not differ significantly between the groups. The incidence of grade II-IV acute GVHD was 40% (four patients died, 13%) in the PBSC group and 20)% (three patients died, 8%) in the BM group, respectively (P < 0.05, log-rank). No signs of aGVHD were found in 19% of the patients in the PBSC and 27% in the BM group. Our results indicate that allogeneic PBSCT does lead to a significantly faster leukocyte engraftment. The significant increase with regard to the incidence and shorter time of onset of severe aGVHD in PBSC patients, compared to marrow transplant patients, need to be confirmed in a randomised trial.
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PMID:A comparative study of peripheral blood stem cell vs bone marrow transplantation from unrelated donors (MUD): a single center study. 1093 83

Overall, the MRC Adult Leukaemia Trials have been successful, in that since the 1970s they have demonstrated a stepwise improvement in outcome. Examination of the survival curves shows the DFS rate at 5 years in UKALL Trial 1 of 5% rising to 38% in UKALL Trial XII (year 2000). Unfortunately, compared with children with ALL, these results in adults must be regarded as poor, because in the UKALL children's trials the EFS rate at 5 years for a child entered in the year 2000 is expected to be above 80%. With a low proportion of all adults entered into randomized trials, one cannot be certain that improvements result from treatment rather than patient selection. Only recently have randomized trials in adults become large enough to detect plausible treatment effects. The authors believe that the main contribution of these trials so far, confirmed by other groups, is in examining prognostic features in al patients and finding that age and the presence of the Ph chromosome, independent of WBC count, gender, and cell type, is the main feature for predicting outcome. The UKALL XII trial will provide valuable information on the relative merits of transplantation and molecular studies of MRD. An in-depth study of a large number of Ph chromosome-positive ALL leukemias will also provide information on which to base future studies. Preliminary data suggest that all Ph-positive patients should undergo some sort of allograft early after CR is achieved, because these patients are not rescued by BMT after relapse. At the time of the publication of this article, preliminary studies suggest that STIs may not be as effective in Ph-positive ALL as in chronic granulocytic leukemia. The challenge for the future is to understand the biologic role of age and its impact on outcome so as to overcome "ageism" in adult ALL.
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PMID:The Medical Research Council trials in adult acute lymphocytic leukemia. 1114 26


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