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)

A total of 239 patients with chronic myeloid leukaemia (CML) in chronic phase awaiting bone marrow transplantation (BMT) from an HLA-identical sibling donor were randomized to receive, as part of their conditioning, splenic irradiation (SI+) or no splenic irradiation (SI-). There was no difference between the SI+ and SI- groups regarding the distribution of age, sex, donor/recipient sex combination and blood counts at diagnosis and at BMT. Survival, leukaemia-free survival (LFS), incidence of transplant-related mortality, incidence of rejection and probability of relapse do not differ between the 117 SI+ and the 118 SI- patients at a median follow-up time of 2.5 years (minimum 0.5 years). LFS at 30 months is 56% (SE 5%) for the SI+ and 51% (SE 6%) for the SI- group (p = 0.65). LFS is better for younger patients (less than 25 years), for patients without T cell depletion and for those with a low white blood cell count at diagnosis (less than 30 x 10(9)/l) (p less than 0.05). It is worst for male recipients of a female marrow (p less than 0.05). The incidence of graft-versus-host disease grade greater than or equal to II was higher in the SI+ group, though not significantly. We conclude that routine splenic irradiation prior to BMT for patients with CML is of no benefit and should not be used as a routine procedure.
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PMID:No advantage for patients who receive splenic irradiation before bone marrow transplantation for chronic myeloid leukaemia: results of a prospective randomized study. 152 4

Between July 1986 and March 1991, 16 patients who had relapsed after T-lymphocyte depleted bone marrow transplantation (BMT) for chronic myeloid leukaemia (CML) received a second transplant using unmanipulated marrow cells from the same HLA-identical sibling donor. The median numbers of days from first BMT to haematological relapse and to second BMT were 557 (range 273-1543) and 1211 (range 476-2310) respectively. 11 patients were in uncomplicated chronic phase at time of second BMT, and five had more advanced disease. As conditioning for second BMT, eight patients received various combinations of cytotoxic drugs, and eight received high-dose busulphan alone. Eight (50%) patients survive at a median of 424 d post-second BMT (range 158-1789) and all are free of leukaemia by conventional criteria: five had been conditioned with high-dose busulphan alone. Causes of death in the eight patients who died included relapse (n = 2), graft-versus-host disease (n = 2), interstitial pneumonitis (n = 2), and infection (n = 2). We conclude that patients relapsing into chronic phase after BMT with T-lymphocyte depleted donor marrow may be offered the option of second BMT with unmanipulated marrow from the original donor. Conditioning with high-dose busulphan alone may be safer than use of more intensive schedules.
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PMID:Second transplants for patients with chronic myeloid leukaemia in relapse after original transplant with T-depleted donor marrow: feasibility of using busulphan alone for re-conditioning. 153 8

Twenty-one patients (median age = 34, range = 10-49; F:M = 7:14) received a preparative regimen consisting of busulfan 4 mg/kg/day x 4, cytosine arabinoside 2 g/m2/12 h x 4 and cyclophosphamide 60 mg/kg/day x 2 ('BAC' regimen) for allogeneic bone marrow transplantation. Out of 12 patients with acute myeloid leukemia (AML), two were in first remission, six were in second remission and four had resistant, relapsed disease or prolonged marrow aplasia after induction chemotherapy. Five of the 12 patients with AML had secondary AML. Four patients had transfusion-dependent myelodysplastic syndrome. Three patients with chronic myeloid leukemia were in the accelerated phase and two were in the blastic phase. Organ toxicities related to the preparative regimen were graded. Liver toxicity occurred in 11 patients, two of these were fatal veno-occlusive disease (VOD) (10%). Nineteen of the 21 patients had grade 2 or less diarrhea, and 13 also had mucositis. One patient developed grade 3 cardiac toxicity, and one other patient had grade 1 skin toxicity. Four patients had gross hematuria related to treatment (19%). No renal, pulmonary or CNS toxicities were encountered. Ten patients have died, two from regimen-related hepatic VOD. Of the remaining eight deaths, four were from respiratory failure in four patients (one case each of Pneumocystis pneumonia, CMV pneumonia, bronchiolitis obliterans associated with chronic graft-versus-host disease, and interstitial pneumonitis complicated pulmonary emboli), and one patient each from GI bleeding, cardiac arrhythmia, sepsis and CNS bleeding. Thus far, only one patient transplanted for secondary AML in second remission relapsed at day 230.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Allogeneic bone marrow transplantation in high-risk myeloid disorders using busulfan, cytosine arabinoside and cyclophosphamide (BAC). 154 49

The reciprocal translocation (9;22)(q34;q11) is highly characteristic of chronic myeloid leukemia (CML) and the pericentric inversion inv(16)(p13q22) is almost only found in acute nonlymphocytic leukemia of the myelomonocytic subtype (ANLL M4). Only twice before have an inv(16) and a t(9;22) been found in the same cells, and both times the patients seemed to have de novo ANLL M4. We describe the case of a 21-year-old man who in July 1986 presented with a clinically and hematologically classic chronic phase CML. Treatment with busulfan led to no improvement; instead in September 1986 he developed blast crisis with ANLL M4Eo morphology. He was now cytogenetically examined and the karyotype 45,X,-Y,t(9;22)(q34;q11),inv(16)(p13q22) was found. Southern blot analysis of the bone marrow DNA sampled at this time revealed a standard rearrangement in the 3' end of the M-bcr. Intensive cytostatic treatment caused cytopenia followed by complete hematologic, clinical, and cytogenetic reversal to chronic phase CML, so that in January 1987 the bone marrow karyotype was 46,XY,t(9;22)(q34;q11). Persistent splenomegaly was treated with splenectomy, and a chloroma of the skin was removed by irradiation. In March 1987 he received an allogeneic bone marrow transplant. Since then his only medical problem has been mild graft-versus-host disease; he is well and is working full time as a blacksmith.
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PMID:Acute myelomonocytic leukemia with inv(16)(p13q22) complicating Philadelphia chromosome positive chronic myeloid leukemia. 155 89

A 43-year-old man developed the nephrotic syndrome 26 months after allogeneic bone-marrow transplantation for chronic myeloid leukemia. This occurred during an exacerbation of graft-versus-host disease (GVHD) and both problems remitted after therapy with cyclosporine and prednisolone. Renal biopsy showed ultrastructural and immunofluorescence evidence of membranous nephropathy. Anti-nuclear antibodies (but not antiglomerular or anti-renal tubular epithelial antibodies) were detected in his serum. Experimental GVHD in mice has been associated with immune complex glomerulonephritis and the presence of IgG autoantibodies which has been attributed to abnormal T (donor)/B (recipient) cell co-operation. This association can be extrapolated to the human GVHD where autoantibody formation is better described than immune complex glomerulonephritis.
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PMID:Membranous nephropathy with graft-versus-host disease in a bone marrow transplant recipient. 156 14

Only a minority of all patients with CML can today be treated by allogeneic bone marrow transplantation (BMT) but the probability of cure for such patients is high. The complications of BMT are similar to those that occur following transplant for other diseases, notably GVHD, pneumonitis and infections. Of special interest is the demonstration that a graft-versus-leukaemia effect plays a role in the cure of CML. Studies using the polymerase chain reaction to detect minimal residual disease (BCR/ABL transcripts) may prove useful in predicting relapse and optimizing conditioning schedules. It is now important to test whether BMT can be equally successful in older patients (over 50 years) and in those lacking HLA-identical sibling donors. For other patients autografting may offer the possibility of achieving complete cytogenetic remission and perhaps prolonging life.
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PMID:Bone marrow transplantation for chronic myeloid leukaemia. 157 36

The safety and possible efficacy of recombinant human granulocyte-macrophage colony-stimulating factor (rhGM-CSF) were evaluated in 40 consecutive patients who received transplants from unrelated donors. rhGM-CSF was administered by 2-hour daily intravenous infusion from day 0 to day 20 or day 27 after the marrow infusion. These patients were compared with 78 historical patients who received transplants from unrelated donors who did not receive rhGM-CSF. The rhGM-CSF-treated patients were older (P = .037) and were treated less frequently in laminar air flow rooms (P = .005) than were control patients. However, the rhGM-CSF-treated group had a higher proportion of "good risk" patients with chronic myelogenous leukemia in chronic phase (P = .006) than did the comparison group (P = .017), rendering comparisons of transplant-related complications not meaningful. rhGM-CSF was well tolerated and did not adversely increase the incidence of graft rejection or increase the incidence and severity of acute graft-versus-host disease. The median day the absolute neutrophil count reached 500/mm3 in patients who received rhGM-CSF was day 21, which was not different from that of historical patients. Nevertheless, the numbers of febrile days and septicemic episodes within the first 28 days in patients who received rhGM-CSF were less than in historical patients. The probability of nonrelapse mortality at 1 year in patients who received rhGM-CSF was 22%. In view of the retrospective nature of the control group, we cannot conclusively determine whether rhGM-CSF administration was beneficial. A prospective, randomized controlled study of rhGM-CSF is required to confirm these suggestive data.
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PMID:Phase II trial of recombinant human granulocyte-macrophage colony-stimulating factor in patients undergoing allogeneic bone marrow transplantation from unrelated donors. 158 9

It is generally accepted that patients with chronic myelogenous leukemia in chronic phase under the age of 50 years who have HLA-identical siblings, should be offered bone marrow transplantation within the first year of diagnosis. The projected disease-free survival for these patients is 70% to 80% at 4 years, and most of these will prove to have been cured. Results of bone marrow transplantation for patients with more advanced disease are less promising. For transplant conditioning there is no important difference between cyclophosphamide plus total-body irradiation and busulphan plus cyclophosphamide. Nonenlarged spleens require neither splenectomy nor additional radiotherapy. The use of cyclosporine and methotrexate is currently the optimal approach to graft-versus-host disease prevention. Fewer good results are obtained with "matched" volunteer marrow donors. Use of the polymerase chain reaction to monitor residual BCR-ABL transcripts after bone marrow transplantation may prove useful in identifying patients at increased risk for relapse. Autografting may offer the prospect of prolonged life or even cure for patients without suitable allogeneic donors.
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PMID:Bone marrow transplantation for chronic myelogenous leukemia. 159

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

We analysed data from 114 recipients of HLA-identical sibling transplants who relapsed and received a second transplant between 1978 and 1989. Twenty-nine patients had acute lymphoblastic leukemia, 46 acute myeloid leukemia and 39 chronic myelogenous leukemia. Median (range) interval between first and second transplants was 15 (1-80) months. Following the second transplant, graft failure occurred in 2%, acute graft-versus-host disease (GVHD) in 27% and chronic GVHD in 21% of patients at risk. Risks of interstitial pneumonia and hepatic veno-occlusive disease were higher after the second than the first transplant. Two-year probabilities (95% confidence interval) of treatment-related mortality, relapse and leukemia-free survival were 41% (30-53%), 65% (53-75%) and 21% (14-30%), respectively. Leukemia-free survival was 7% (2-19%) among patients relapsing less than 6 months after their first transplant, with high rates of both relapse, 77% (49-92%), and treatment-related mortality 69% (46-85%). In contrast, leukemia-free survival was 28% (19-41%) in those relapsing more than 6 months after the first transplant; in this group the probability of relapse was 59% (45-72%) and treatment-related mortality 30% (20-43%). Factors correlated with better outcome included a diagnosis of chronic myelogenous leukemia, relapse more than 6 months after the first transplant, acute leukemia in remission prior to the second transplant and good performance status.
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PMID:Second HLA-identical sibling transplants for leukemia recurrence. 160 Apr 15


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