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)

Eight patients with chronic myeloid leukemia relapse after allogeneic BMT were treated with IFN-alpha and buffy coat transfusions (BC) of the bone marrow donor. The antileukemic effect of this treatment was directly demonstrated in 4 patients by the disappearance of Philadelphia chromosome-positive metaphases or the loss of detectable BCR-ABL transcripts by polymerase chain reaction. In 2 patients in whom cytogenetic or polymerase chain reaction analysis was not performed, a change in hemopoietic chimerism with recurrence of donor-type hemopoiesis was demonstrated. Two patients, both treated in advanced stages of hematological relapse after BMT, did not respond. However, severe side effects of the treatment were observed: graft-versus-host disease (GVHD) occurred in 5 patients. Two of these patients progressed to severe chronic GVHD and 1 patient ultimately died of this complication. GVHD occurred in 5 of the 6 responding patients; one patient responded without developing clinical symptoms of GVHD. Six patients developed bone marrow hypoplasia after IFN/BC treatment, and pancytopenia occurred in 4 patients. None of these 4 patients recovered spontaneously and 2 patients died of complications of pancytopenia (cerebral bleeding, infection). Our results demonstrate that treatment of chronic myeloid leukemia relapse with IFN and BC transfusions is highly effective in patients with relapse in chronic phase. The occurrence of GVHD and pancytopenia, however, resulted in a high treatment-associated morbidity and mortality. Whereas a response to treatment was observed in 1 patient without GVHD, indicating that GVHD and a graft-versus-leukemia effect may be clinically separable, bone marrow hypoplasia occurred in all responding patients.
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PMID:Interferon-alpha and donor buffy coat transfusions for treatment of relapsed chronic myeloid leukemia after allogeneic bone marrow transplantation. 824 10

There is no doubt that the poor reputation of T-cell depleted bone marrow transplant arises from its use in CML patients, where an increase in graft rejection and, above all, in leukaemia relapse has been reported by almost all centres. Evidence suggests that the standard conditioning regimen (once thought to be sufficiently immunosuppressive and myeloablative in unmanipulated transplants) should no longer be considered adequate when the immunological balance has shifted in favour of unopposed host-versus-graft reactivity and the GvL effect is lacking. Since GvHD remains the major problem in BMT, we suggest T-cell depletion should be considered the most effective method for GvHD prophylaxis but the cytoreductive effect of the conditioning regimens and the anti-leukaemia immune reactivity should be enhanced.
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PMID:Is there any future for T-cell depleted bone marrow transplantation in chronic myeloid leukaemia? 825 97

The management of CML patients with some evidence of disease after BMT depends on the molecular, cytogenetic and hematological findings of relapse. Presently, a number of technical and biological problems do not allow to draw any definitive conclusion on the prognostic significance of Minimal Residual Disease detected by PCR. A positive PCR, particularly if observed late after BMT, leads to increase the frequency of cytogenetic examinations, but a therapeutic intervention is not justified. The criteria to define the cytogenetic relapse are not still established. Therefore it is difficult to interpret the reappearance of Ph-1 chromosome after BMT as disease recurrence invariably progressing towards the hematological phase. However, alpha-Interferon, donor buffy-coat infusion or their association should be considered in the treatment of patients for whom the cytogenetic relapse has been confirmed. The therapeutic approach to patients with hematological relapse is mainly depending on the phase of disease. The single, sequential or combined use of chemotherapy, alpha-IFN, donor buffy-coat infusion and second transplant has been shown to be effective in restoring donor hematopoiesis in several patients who relapsed either in chronic or advanced phase. Prospective, randomized, multicentre trials on CML relapse after BMT should be planned.
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PMID:What does one do for the CML patient in relapse after allogeneic bone marrow transplantation? 825 99

Immune mechanisms superimposed to the myeloablative conditioning regimens exert an additional powerful effect in eradicating leukemia and in achieving immunological control of minimal residual disease. The impact of GVHD-independent GVL has been evaluated to be absent, or near absent, in ALL, about 30% in AML and about 40% in CML. While until little time ago most of the evidence in favor of an immune antileukemia mechanism exerted by allo BMT in CML was indirect, based on the lack of GVL, there is now solid evidence of a positive type, based on the antileukemia effect of donor lymphocyte infusions in patients having relapsed after transplant. There are three lines of indirect clinical evidence for GVL in CML: they include the classical linkage between GVHD and reduced relapse rate, increased relapse rate after identical twin allografts, and increased relapse risk after effective GVHD prophylaxis, with T lymphocyte depletion in the foreground. The eradicating effects of donor lymphocyte infusions in relapsed patients are the ultimate demonstration that allogeneic immune competent cells are capable of recognizing and destroying the Ph-positive clone. However the frequency of irreversible aplasia indicates that donor lymphocytes act in the same way on residual host hematopoiesis, so that a second graft, without repeat conditioning, should be programmed for such cases.
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PMID:The graft versus leukemia (GVL) effect after allogeneic bone marrow transplantation for chronic myelogenous leukemia (CML). 825

Two hundred and twenty-nine patients with chronic myeloid leukaemia in chronic phase awaiting bone marrow transplantation from an HLA-identical sibling donor were randomized as part of their conditioning, to receive splenic irradiation (SI+, 115 patients), or not (SI-, 114 patients). Both groups were identical in regard to age, sex, donor/recipient sex combination and disease activity. Survival, leukaemia-free survival, incidence of transplant-related mortality, acute and chronic graft versus host disease, incidence of rejection and probability of relapse were not different in either groups at a median follow-up time of 4.5 years (minimum follow-up 2 years). Recovery of peripheral white blood cell counts to 1 x 10(9)/l but not of platelet counts to 50 x 10(9)/l was significantly faster in patients with SI+ (21 vs 24 days). This small benefit does not justify routine splenic irradiation prior to BMT, in CML.
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PMID:Splenic irradiation before bone marrow transplantation for chronic myeloid leukemia: update of a prospective randomized study. 825 1

This is an interim report of the Roferon A/ABMT protocol by ICSG on CML aimed at investigating the feasibility and potential of combining treatment with alpha-IFN with ABMT in Ph+ CML. Of 675 Ph+ CML patients recruited between January 1989 and January 1991 by 44 Italian institutions, 398 were 55 or less years old and eligible for the protocol. Of 132 patients who completed IFN treatment 118 had evaluable karyotype; of these only 48 showed > 25% Ph--metaphases and were eligible for BM harvest. In 24 patients BM was collected and 13 were submitted to ABMT. The major causes of drop out from the protocol were shift to allogeneic BMT, accelerated blastic phase, patient refusal and logistic problems. Data on hematologic reconstitution are presently available in 11 patients: Neutrophils were > 0.5 x 10(9)/l in 23 days (median), (range 16-40 days); platelets reached 50 x 10(9)/l in 28 days (median), (range 25-100 days). One patient had a very delayed BM take and was rescued with autologous peripheral blood stem cells collected at diagnosis.
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PMID:Karyotypic conversion by interferon as preparative treatment for autologous BMT in Ph positive CML. Italian Cooperative Study Group (ICSG) on Chronic Myeloid Leukemia. 825 9

To evaluate the prognostic features of Ph+ CML patients treated by allogeneic BMT or by IFN, we reviewed the data of 50 consecutive pts who were transplanted between 1984 and 1988 and of 180 consecutive patients who were assigned to continuous IFN treatment between 1986 and 1988. In the BMT group, Sokal's system predicted survival (transplant-associated mortality). In the IFN group, Sokal's system, platelet count, and peripheral blood blast cell percentage predicted karyotypic response. In this group, survival was related more significantly with blast cell than with Sokal's score. The strongest predictor of survival was karyotypic response to IFN, with a 4-year survival of 94% for responders vs. 56% for non-responders.
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PMID:Prognostic factors in chronic myeloid leukemia. Relationship with interferon and bone marrow transplantation. The Italian Cooperative Study Group on Chronic Myeloid Leukemia. 825 20

Bone marrow transplantations have a definite role in treatment of leukemias and lymphomas. In acute myeloid leukemia and CML an allogeneic transplant using an HLA identical donor certainly provides a far superior survival than chemotherapy. Patients with Ph' chromosome need to be transplanted in first remission if a suitable donor is available. In recurrent lymphomas the best results are achieved if the patient is transplanted in complete remission. Transplantation done using minor mismatched family donors or unrelated donors are still considered experimental and more data is needed before final recommendations can be made. Availability of supportive services is an absolute must prior to establishing transplant program. Selection of patients for transplantation should be done after carefully reviewing the indications and discussing with the family the emotional, financial and physical burden of the procedure. For selected indications in leukemias and lymphomas, BMT may be the only viable treatment option and therefore must be considered.
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PMID:Bone marrow transplantation. 826 90

A significant proportion of patients relapse after allogeneic BMT for CML. These relapses have been treated by induction of a graft-versus-leukemia effect by transfusing donor leukocytes. We have treated a 27-year-old woman with interferon and donor leukocyte transfusion and a complete haematological and cytogenetic remission was obtained coincident with the onset of GVHD. Her course was complicated by prolonged and profound pancytopenia which was fully reversed by the administration of rGM-CSF. She remains in CR with mild dermatomyositis due to chronic GVHD 17 months after the procedure.
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PMID:Reinduction of remission of chronic myeloid leukemia by donor leukocyte transfusion following relapse after bone marrow transplantation: recovery complicated by initial pancytopenia and late dermatomyositis. 827 41

Patients with chronic granulocytic leukemia (CGL) can be classified in different groups according to risk factors at diagnosis (Sokal). The aim of the present study was to assess the impact of Sokal's risk factors in 100 patients with CGL undergoing allogeneic BMT. Patients were in first chronic phase (CP) (n = 65), or with advanced disease (n = 35), grafted from an HLA-identical sibling following conditioning with cyclophosphamide and total body irradiation (TBI). Median follow up for survivors is 1783 days (429-3533 days). Variables recorded at diagnosis to calculate Sokal's prognostic index were: leukocyte, platelet and peripheral blood blast cell counts, age and spleen volume. The median value of the Sokal index was 0.87. Projected survival for all patients at 9 years was 28% (95% confidence limits (CL) 6-49), 48% (34-62) for first CP patients and 15% (0-36) for more than first CP patients (p = 0.04). Survival was 25% and 31% for all patients with a Sokal index of < 0.87/> or = (p = 0.07) and 55% vs 39% for first CP patients only (p = 0.03). The relapse rate was similar for patients with Sokal index < 0.87/> or = (41% vs 39%, p = 0.9) and this was also true for first CP patients (33% vs 26%, p = 0.8). In multivariate analysis, an interval between diagnosis and BMT of > 2 years was the most significant negative predictor for survival for the whole group of patients (p = 0.01) and more so for first CP patients (p = 0.0004).(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Multivariate analysis of risk factors for survival and relapse in chronic granulocytic leukemia following allogeneic marrow transplantation: impact of disease related variables (Sokal score). 829 54


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