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

We have analysed the results of treating 140 consecutive patients with chronic myeloid leukaemia (CML) in chronic phase by bone marrow transplantation (BMT) using marrow from HLA-identical siblings performed between February 1981 and July 1991. Three different regimens were used sequentially to prevent graft-versus-host disease (GVHD): cyclosporin A (CsA) alone (n = 39), T-cell depletion of donor marrow (n = 51) and CsA with methotrexate (MTX) (n = 50). Eighty-four patients (61%) survive at a median of 49 months from BMT (range 3-120). The actuarial overall and leukaemia-free survivals at 5 years were 52% and 41% respectively. The actuarial probabilities of leukaemia-free survival and haematological relapse at 2 years for the CsA only group were 65% and 4%, for the T-cell depletion group 40% and 41% and for the CsA/MTX group 68% and 6% respectively. For the T-cell depletion group the probability of leukaemia-free survival was significantly lower (P less than 0.001) and the probability of relapse significantly higher (P less than 0.001) than for other methods of GVHD prophylaxis; differences between the other two groups were not significant. Previous reports that T-cell depletion with Campath-1M results in a high rate of relapse are confirmed. Patients in the CsA/MTX group have been monitored with cytogenetic and polymerase chain reaction studies for residual BCR/ABL transcripts. We conclude that the combination of CsA/MTX is currently the best available approach to prevention of GVHD after BMT for CML and in our hands it is not associated with a major risk of relapse.
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PMID:HLA-identical sibling donor bone marrow transplantation for chronic myeloid leukaemia in first chronic phase: influence of GVHD prophylaxis on outcome. 139 Feb 11

Twenty-two patients (16 male, six female; median age 34 years, range 16-49) with acute myeloid leukemia (1st complete remission (CR), n = 9), acute lymphocytic leukemia (1st CR, n = 5), chronic myeloid leukemia (chronic phase n = 5, accelerated phase n = 1), malignant lymphoma (n = 1) and myeloma (n = 1) were transplanted with unmanipulated donor bone marrow after standard conditioning including the monoclonal antibody Campath-1G daily from day -4 to day 0. No further graft-versus-host disease (GVHD) prophylaxis was given. All patients engrafted and neither graft failure nor rejection were observed. Acute GVHD grade I (skin) was seen in 12 out of 21 patients at risk. Acute GVHD grade II (skin) occurred in two patients. Severe GVHD (grade III, IV) of the gut, liver and skin developed in two patients. The overall incidence of severe acute GVHD (II-IV) was 19% of the patients at risk. Chronic GVHD (skin only) was seen in eight patients (42%) (six of extensive severity). A total of 14 patients died, the causes being relapse (four), direct cytotoxic drug toxicity (one), a GVHD (two), disseminated varicella zoster (one), systemic tuberculosis (one), interstitial pneumonitis (three) and veno-occlusive disease (two). These results indicate that the intravenous administration of Campath-1G may have reduced the incidence of severe acute GVHD without the occurrence of graft failure. However, the incidence of chronic GVHD does not appear to have decreased.
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PMID:In vivo use of Campath-1G to prevent graft-versus-host disease and graft rejection after bone marrow transplantation. 160 Apr 13

The Polymerase Chain Reaction (PCR) was used to evaluate minimal residual disease in 21 Ph+ CML patients at various intervals after allogeneic bone-marrow transplantation (ABMT) by amplification of bcr-abl cDNA. All patients were cytogenetically Ph- at the moment of molecular analysis. Of these 76% were PCR negative, 24% positive for bcr-abl transcripts. 100% of the Cyclosporine A/Methotrexate treated patients (7/7) were negative. Severe chronic GvHD was twice as frequent in PCR positive patients (60%) than in negative ones (31%). The only patient who relapsed during follow up was PCR positive. The two longest survivors were PCR negative. These data are still insufficient for assessing the predictive value of PCR analysis in CML. Patients. 25 patients with Ph+ CML at diagnosis were enrolled in this study. Two died soon after BMT because of infection for failure of engraftment/early relapse, two were Ph chromosome positive and PCR+, and were therefore dismissed from this study. All remaining 21 patients were cytogenetically Ph- at the time of molecular analysis and underwent ABMT from matched donors. All patients were conditioned with cyclophosphamide and TBI: 330 cGy the three days prior to transplantation (990 cGy total, treatment B), or 200 cGy two times daily for three days (1200 cGy total, treatment A). In 3 cases the marrow was treated for GvHD prophilaxis with Campath alone or Campath plus BT 5/9 monoclonal antibodies (1). All patients were treated with Cyclosporin A (CS) 5 mg/kg i.v. from the day prior to transplantation until 25-30 days after; 9 of these were treated with CS plus Methotrexate (MTX).
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PMID:An assessment of chimeric transcript detection in CML patients after bone marrow transplantation. 187 98

Adherent lymphokine activated killer (ALAK) cells are a subpopulation of activated natural killer (NK) cells with MHC unrestricted antitumour activity distinguished by their propensity to adhere to plastic in the presence of interleukin-2 (IL-2). We generated ALAK cells from seven patients with chronic myeloid leukaemia (CML) following Campath-1-depleted bone marrow transplantation (BMT). Five had relapsed and were in chronic phase, one had cytogenetic evidence of relapse and one had prior evidence of cytogenetic relapse but was in complete remission at time of study. Phenotypically the ALAK cells included both CD56+/CD3- NK cells and CD56-/CD3+ T cells. The CD3- subpopulation were studied cytogenetically and their functional activity tested in a 4 h 51Cr release cytotoxicity assay using the pretransplant leukaemia cells as targets. Cytogenetic studies showed that the ALAK cells from six patients were Ph negative, and where donor and recipient were sex mismatched, ALAK cells were exclusively of donor origin. In one patient ALAK cells were Ph positive and of recipient origin in eight of nine metaphases. In the 51Cr release assay the ALAK cells showed significant lysis of the pretransplant leukaemia in five of the seven patients tested. These data indicate that in CML patients who relapse post-BMT the NK cells are usually of donor origin but may be recipient-derived. In most patients these ALAK cells have antileukaemic activity in vitro.
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PMID:Origin and function of adherent lymphokine activated killer cells in patients with chronic myeloid leukaemia who relapse following bone marrow transplantation. 199 98

From April, 1985, to February, 1989, 102 consecutive patients received unrelated donor bone marrow transplantation therapy for chronic myelogenous leukemia (CML) at four centers. Median age of the group was 31 years (range, 4.5 to 51 years). Fifty-four patients were in first chronic phase (CP) at time of transplantation, and 48 had evidence of more advanced disease (AD) (accelerated phase, 32; blast crisis, 9; second CP, 7). In 44 cases, the donor and recipient were identical at the HLA A, B, and DR loci and were nonreactive in bidirectional mixed leukocyte culture (MLC) ("matched"). In 58 cases, nonidentity between donor and recipient could be determined at at least one HLA locus or in bidirectional MLC ("mismatched"). Fifty-eight patients were prepared for transplantation with a combination of cyclophosphamide and fractionated total body irradiation (FTBI) and received acute graft-versus-host disease (GVHD) prophylaxis consisting of methotrexate alone or in combination with cyclosporine, prednisone, or antithymocyte globulin (ATG). In 44 cases, patients received preparative agents in addition to cyclophosphamide and FTBI, and marrow depleted of mature T lymphocytes by ex vivo incubation with either anti-CD3 antibody plus complement (n = 24) or Campath-1 (n = 20). Engraftment defined by a peripheral blood neutrophil count greater than 0.5 X 10(9)/L was demonstrated in 92 cases and occurred at a median of 22 days (range, 11 to 46 days). In 10 cases, peripheral blood evidence of engraftment did not occur, and in one case, engraftment was followed by aplasia. Hematologic relapse was seen in four cases. Recurrence or persistence of the Ph1 chromosome without evidence of hematologic relapse occurred in four additional cases. The incidence of grade II to IV acute GVHD is 65% (95% confidence interval [CI], +/- 10%). After adjustment for recipient age and donor matching status, recipients of T lymphocyte-depleted donor marrow had a significantly lower incidence of grade II to IV acute GVHD (P less than .01); however, T depletion was not significantly associated with improved survival (P = .34), disease-free survival (P = .51), or increased incidence of relapse (P = .39). Of 102 patients, 46 are alive, with a median survival of 12 months (range, 3 to 46 months), and the Kaplan-Meier estimate of disease-free survival is 29% (95% CI, +/- 9%) for the entire group at 2 1/2 years.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Therapy for chronic myelogenous leukemia with unrelated donor bone marrow transplantation: results in 102 cases. 232 22

We treated 17 patients with chronic myeloid leukemia (CML) by bone marrow transplantation using marrow from human leukocyte antigen (HLA)-matched unrelated donors. Patients were conditioned with a combination of in vivo monoclonal antibodies, chemotherapy with daunorubicin (n = 7) or busulfan (n = 10) and cyclophosphamide, and both total body and total lymphoid irradiation. Donor marrow was depleted of T cells by incubation with monoclonal antibodies of the Campath series. Fourteen (88%) of 16 evaluable patients had sustained engraftment. Four (27%) of the 15 evaluable patients developed acute graft-versus-host disease (GVHD) of grade II or greater, and 4 of 12 evaluable patients developed chronic GVHD. Three patients developed hematological and two developed cytogenetic evidence of relapse. Eight patients (47%) survive at a median follow-up of 32 months (range 10-51 months), giving an actuarial survival of 44%. Five patients remain alive without evidence of hematological or cytogenetic relapse, giving an actuarial disease-free survival of 27%. Pneumonitis caused or contributed to death in six of the nine patients who died. We conclude that T-cell depletion can prevent the severest forms of GVHD but also increases the risk of relapse after transplant with unrelated donors, as it does with HLA-identical siblings. Nevertheless the use of matched unrelated donors should be considered for CML patients who lack HLA-identical siblings.
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PMID:Bone marrow transplantation for chronic myeloid leukemia: the use of histocompatible unrelated volunteer donors. 233 31

Pulmonary function was measured before and at intervals after treatment in 44 patients who received a bone marrow transplant for chronic myeloid leukaemia in the chronic phase. All patients were treated with cytotoxic drugs, total body irradiation, and post-graft immunosuppression. Thirty four patients surviving for 12 months were followed at three monthly intervals and 16 patients for 24 months. Fifteen patients received unmanipulated donor marrow cells and 29 patients received donor marrow cells depleted of lymphocytes ex vivo with the monoclonal antibody Campath-1. The 21 patients treated early in this study received 10 Gy of total body irradiation whereas the 23 patients treated more recently, who were all T lymphocyte depleted, received 12 Gy. Pretransplant lung function for the group was normal and was similar in survivors (n = 34) and nonsurvivors (n = 10), and in smokers (n = 8) and non-smokers (n = 36). (Carbon monoxide transfer factor--TLCO) was under 75% of predicted normal in nine patients before transplantation. TLCO, carbon monoxide transfer coefficient (KCO), FEV1, and vital capacity (VC) values were lower 6 and 12 months after bone marrow transplant than initially. The greatest decline was in TLCO, from an initial value of 89% to 66% at 6 and 70% at 12 months. The 16 longer term survivors showed significant recovery of function between 6 and 24 months after bone marrow transplant for TLCO, KCO, and VC, the increase ranging from 6.3% to 7.3% predicted. Airflow obstruction (FEV1/VC ratio less than 70%) developed in one patient. The major factors associated with deterioration in pulmonary function at 6 and 12 months after transplantation in the 34 survivors (stepwise multiple regression analysis) were (a) transplantation with T cell depleted donor marrow (p less than 0.005) and higher total body irradiation dose (p less than 0.02) with a fall in KCO and an increase in the FEV1/VC ratio; (b) chronic graft versus host disease with a fall in VC (p less than 0.01); and less fall in KCO (p less than 0.01); and (c) acute graft versus host disease with a fall in FEV1 (p less than 0.01). It is considered that most patients who survive the short term risks of bone marrow transplant have only minor long term impairment of pulmonary function.
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PMID:Pulmonary function after bone marrow transplantation for chronic myeloid leukaemia. 304 53

We analysed the incidence of graft failure, graft-versus-host disease (GVHD) and relapse of leukaemia in 208 patients undergoing allogeneic bone marrow transplantation (BMT) for chronic myeloid leukaemia in chronic phase in eight transplant centres in Europe and the United States. 106 patients received unmanipulated donor bone marrow (Group 1) and 102 patients received marrow depleted of T-cells by incubation with the monoclonal antibodies Campath-1 or CT-2 and complement (Group 2). The incidence of graft failure was higher and of GVHD was lower in Group 2 than in Group 1. Relapse of leukaemia occurred more frequently in patients in Group 2 than in Group 1 (17 v. 2, P less than 0.001). Multivariate analysis showed that the following factors were associated with an increased risk of relapse: the use of T-cell depletion, the absence of GVHD and a high platelet count at the time of admission for transplant. The findings support the concept that a graft-versus-leukaemia effect mediated by T-lymphocytes is important for cure of leukaemia after BMT.
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PMID:Bone marrow transplantation for chronic myeloid leukaemia in first chronic phase: importance of a graft-versus-leukaemia effect. 329 30

Between December 1983 and November 1985 we treated 39 patients with chronic myeloid leukaemia by chemoradiotherapy and transplantation from HLA-identical sibling donors using bone marrow that had been depleted of T cells ex vivo with the rat monoclonal antibody Campath-1. Twenty-eight of the patients were in the chronic phase (good-risk group) and 11 patients were in more advanced phases of the disease (accelerated phase or blastic transformation; poor-risk group). Of the patients of good risk 23 (82%) survive; the median duration of follow-up is 461 (range 111-776) days; of the 11 patients of poor risk four survive; the median duration of follow-up is 280 (range 189-658) days. Acute graft-versus-host disease (GVHD) of grade II or greater occurred in three (11%) of the patients of good risk and in six (55%) of the patients of poor risk. In the patients of good risk haematological evidence of relapse was seen in four and cytogenetic evidence of persisting or relapsed leukaemia (based on the finding of Philadelphia-chromosome-positive marrow metaphases more than 6 months after transplant) was seen in three other patients. In comparison with the patients of good risk transplanted with untreated marrow between February 1981 and December 1983, the incidence of acute GVHD was reduced significantly (P less than 0.001) but the risk of leukaemic relapse (including patients with only cytogenetic evidence of relapse) was increased (P less than 0.005). We conclude that T-cell depletion used in this manner may be associated with an increased risk of leukaemic relapse.
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PMID:Bone marrow transplantation for patients with chronic myeloid leukaemia: T-cell depletion with Campath-1 reduces the incidence of graft-versus-host disease but may increase the risk of leukaemic relapse. 333 20

Between May 1989 and February 1994, we performed 48 volunteer unrelated donor BMTs for first chronic phase chronic myeloid leukemia using in vivo T cell depletion for acute graft-versus-host disease (aGvHD) prophylaxis. In 40 cases, adequate material was available to measure the frequency of antirecipient MHC cytotoxic T lymphocyte precursor (CTLp) cells in the blood of potential donors. This supplemented standard serological typing, one-dimensional isoelectric focusing for class I proteins, and allogenotyping for DR and DQ alleles using DNA RFLP analysis in the donor selection process. All recipients were conditioned with cyclophosphamide 120 mg/kg, TBI 1320 cGy, and intravenous Campath 1G. GvHD prophylaxis consisted of CsA, short-course methotrexate, and intravenous Campath 1G. Minimum follow-up in all surviving recipients was 100 days. The development of aGvHD and the probability of leukemia-free survival were compared between the high frequency group (CTLp > 1 in 100,000) (n = 15) and the low frequency group (CTLp < 1 in 100,000) (n = 25). There was a trend for increasing grade of aGvHD, which was statistically significant in the high frequency group when compared with the low frequency group (P = 0.003). Both a high frequency of CTLp (relative risk [RR] = 9.0, P = 0.016) and HLA mismatch (RR = 6.7, P = 0.023) were predictors of severe aGvHD (grade III or IV). Multivariate analysis showed that CTLp group (RR = 3.4, P = 0.015) and CMV status (RR = 3.9, P = 0.008) were predictors of leukemia-free survival. Further investigation showed an interaction between the two, such that CMV seropositive recipients in the high frequency group had a relative risk of 9.4 (P = 0.0001) of treatment failure (death or relapse) when compared with other combinations. We conclude that with our present GvHD prophylaxis regimen, CTLp frequency analysis predicts post-BMT outcome and is a valuable aid in donor selection.
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PMID:Cytotoxic T lymphocyte precursor frequency analyses in bone marrow transplantation with volunteer unrelated donors. Value in donor selection. 776 66


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