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 prospective randomized study was conducted comparing two conditioning regimens for the treatment of patients with chronic myeloid leukemia in chronic phase by marrow transplantation from HLA identical siblings. Sixty-nine patients received 60 mg/kg of cyclophosphamide on each of 2 successive days followed by 6 fractions of total body irradiation each of 2.0 Gy (CY-TBI), and 73 patients received 16 mg/kg of busulfan delivered over 4 days followed by 60 mg/kg CY on each of 2 successive days (BU-CY). There was no significant difference between the CY-TBI and the BU-CY groups in the 3-year probabilities of survival (0.80 for both), relapse (0.13 for both), or event-free survival (CY-TBI, 0.68; BU-CY, 0.71) or in speed of engraftment or incidence of venocclusive disease of the liver. The 4-year probabilities of survival and event-free survival for patients transplanted within 1 year of diagnosis were 0.86 and 0.72, respectively, for each group. Significantly more patients in the CY-TBI group experienced major creatinine elevations. There was significantly more acute graft-versus-host disease in the CY-TBI group. Fever days, positive blood cultures, hospitalizations, and inpatient hospital days were significantly more common in the CY-TBI group than in the BU-CY group. In conclusion, the BU-CY regimen was better tolerated than, and associated with survival and relapse probabilities that compare favorably with, the CY-TBI regimen.
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PMID:Marrow transplantation for chronic myeloid leukemia: a randomized study comparing cyclophosphamide and total body irradiation with busulfan and cyclophosphamide. 1139 26

Between October 1988 and December 1992, 167 patients with leukemia receiving marrow transplants from HLA-identical donors and conditioned with cyclophosphamide (120 mg/kg) were randomized to additional treatment with either busulfan (16 mg/kg, n = 88) or total body irradiation (TBI; n = 79). The busulfan-treated patients had an increased cumulative incidence of veno-occlusive disease of the liver, ie, 12% compared with 1% in the TBI group (P = .009). Furthermore, hemorrhagic cystitis occurred in 24% of the busulfan patients versus 8% in the TBI patients (P = .003). In patients with advanced disease beyond first remission or first chronic phase, transplantation-related mortality was 62% among the busulfan-treated patients compared with 12% among the TBI recipients (P = .002). These differences between the two groups were statistically significant in multivariate analysis. Seizures were seen in 6% of the busulfan-treated patients and were absent in the TBI group (P = .03). Grade II-IV of acute graft-versus-host disease (GVHD) was similar in the two groups, but grade III-IV and chronic disease was more common in the busulfan-treated group (P = .04). Death associated with GVHD occurred in 17% of the busulfan-treated group and 2% of the TBI group (P = .003). Patients treated with busulfan had a 3-year actuarial survival of 62%, which was worse than the 76% among those treated with TBI (P < .03). In multivariate analysis, poor survival was associated with advanced disease (P < .0001), no posttransplant septicemia (P = .0006), grade II-IV GVHD (P = .006), and busulfan treatment (P < .02). The incidence of relapse did not differ between the two groups. Relapse-free survival was also similar in the two treatment groups on analysis of data from all patients, children, patients with early disease, and those with acute myeloid leukemia, acute lymphoblastic leukemia, and chronic myeloid leukemia. However, in adults (P = .05) and patients with advanced disease (P = .005), leukemia-free survival was significantly better in those treated with TBI. We conclude that patients treated with busulfan have more early toxicity and an increased transplant-related mortality in patients with advanced disease. TBI is therefore the treatment of choice, especially in adults and patients with advanced disease. However, busulfan is an acceptable alternative for patients with early disease and for those in whom TBI is not feasible.
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PMID:A randomized trial comparing busulfan with total body irradiation as conditioning in allogeneic marrow transplant recipients with leukemia: a report from the Nordic Bone Marrow Transplantation Group. 816 51

This study examined the role of intrathymic injection of allogeneic spleen cells in induction of donor-specific unresponsiveness to heart allografts in the Lewis-to-ACI rat combination. Intrathymic injection of naive Lewis SC led to rejection in naive or sublethally irradiated (200 rads TBI) ACI recipients at times equivalent to those obtained in control animals. Intrathymic injection of UV-B-irradiated Lewis SC, on the other hand, led to indefinite cardiac allograft survival (> 300 days) in sublethally irradiated ACI recipients; similar treatment failed to prevent rejection of third-party (Wistar Furth) cardiac allografts, which demonstrates the specificity of the immunologic unresponsiveness thus induced. The finding that intrathymic injection of untreated allogeneic SC does not prevent rejection of subsequently transplanted allograft suggests that modulation of major histocompatibility complex class II molecule by methods such as UVB may be critical to induction of unresponsiveness. Inoculation of UV-B donor SC in extrathymic sites (subcutaneous, intraperitoneal and intratesticular) did not significantly prolong graft survival in similarly prepared animals, thus confirming the privileged position of the thymus in the induction of tolerance. When the unresponsive recipients of cardiac allografts were made diabetic at 100 days and rechallenged with a second-set donor-type neovascularized pancreatic islet grafts, three of four animals accepted permanently (> 100 days) the islet grafts, thus indicating tolerance to donor alloantigens. To define the underlying mechanisms of specific tolerance in this model, in vitro MLR and in vivo adoptive transfer studies failed to demonstrate suppressor activity in the long-term cardiac allograft recipients. In contrast CML assays using 51Cr-release showed that T cells obtained from the unresponsive animals had no detectable cytotoxic activity to Con A-stimulated donor blast targets. The latter finding suggests clonal anergy or deletion of cytotoxic T cells to donor alloantigens. Our results confirm the role of the thymus as a privileged site for the induction and maintenance of specific immunologic unresponsiveness to organ allografts and suggest that this approach may be potentially useful in clinical transplantation of immediately vascularized allografts and neovascularized grafts.
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PMID:Induction of donor-specific unresponsiveness to rat cardiac allografts by intrathymic injection of UV-B-irradiated donor spleen cells. 851 24

There are reports of acute graft-versus-host disease (GVHD) after autologous and twin bone marrow transplants but they are controversial because of the difficulty of accurate diagnosis. We report a subject with Philadelphia chromosome-positive CML who received two syngeneic transplants of blood cells. In the first transplant of 2.6 x 10(8) mononuclear cells/kg, no pretransplant conditioning was given; in the second transplant of 4.9 x 10(8) mononuclear cells/kg, pretransplant conditioning therapy consisted of chemotherapy and TBI. Although no symptoms were seen after the first transplant, the second was followed by fever, diarrhea, rash and liver function test abnormalities coincident with engraftment. Symptoms resolved spontaneously. The patient was not on any medication and had not received any transfusions. Our observations suggest either that acute GVHD in a twin transplant is a direct consequence of conditioning or that pretransplant conditioning is a prerequisite for developing features resembling acute GVHD.
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PMID:Acute graft-versus-host disease in a recipient of a twin blood cell transplant. 867 46

Two major problems of unrelated donor transplantation have been an increased incidence of GVHD and graft failure. Even with HLA identity by microlymphocytotoxicity assay and non-reactive MLC, URD marrow transplant recipients have a higher incidence of graft rejection and GVHD. The preparative regimen busulfan 16 mg/kg and cyclophosphamide 120 mg/kg (BuCy2) has been shown to be at least as effective in preparation of recipients with CML of HLA-identical sibling grafts as cyclophosphamide and total body irradiation (Cy/TBI). However, concern about a high rejection rate in URD transplants has prevented most centers from using BuCy2 in this setting. From March 1990 to March 1994, 26 patients underwent URD transplantation following preparation with BuCy2. Patients received either standard cyclosporine and methotrexate or cyclosporine and methylprednisolone for GVHD prophylaxis. Two patients died on day 16 and 20 without evidence of hematopoietic engraftment. Of the 24 patients evaluable for engraftment, 23 (96%) had evidence of donor engraftment defined as an ANC > 0.5 x 10(9)/1. No patient who had initial engraftment had late graft failure. Within our study group the risk of graft rejection or graft failure does not appear to be higher than that reported for URD transplants utilizing TBI-containing regimens.
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PMID:Bone marrow engraftment following unrelated donor transplantation utilizing busulfan and cyclophosphamide preparatory chemotherapy. 872 42

Myeloablative treatment followed by lymphohaematopoietic reconstitution with stem cells from umbilical cord blood (UCB) can cure children with leukaemia. The clinical experience of UCB transplantation with HLA 2- and 3-antigen mismatched siblings is rather limited and there are no reports of such patient being given UCB significantly contaminated with maternal T lymphocytes. In this study, we report our experience in treating a child with chronic myeloid leukaemia in blast crisis who was transplanted using UCB cells from mismatched sibling donor containing a significant number of maternal T cells. The patient received 1.17 x 10(8) nucleated cells/kg after conditioning with Ara-C, busulphan, TBI and cyclophosphamide. GVHD prophylaxis was with cyclosporine and an anti-CD25 monoclonal antibody. Although engraftment was somewhat slow it was complete as documented by cytogenetic analysis and DNA studies. Results of minimal residual disease monitoring by RT-PCR for the hybrid BCR/ABL gene showed no evidence of leukaemic mRNA post-transplant. Acute GVHD, skin only, developed on day +14 but promptly responded to low-dose steroids. The technique used for UCB collection may have cell contamination found. In spite of these potential disadvantages: advanced disease, HLA antigen disparate donor and significant maternal T cell contamination, the transplant was successful and at a follow-up of 14 months the child is well with no evidence of chronic GVHD. Immune naivety of cord blood and lack of immunological reactivity of maternal T cells in this context may have played a significant role in the outcome of this case.
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PMID:Haploidentical cord blood transplant contaminated with maternal T cells in a patient with advanced leukaemia. 873 18

A 6-year-old boy with CML in blastic crisis was transplanted with BM and PBSC from his HLA-mismatched MLC-positive mother following CD34-positive selection. Preconditioning for transplant was with thiotepa, cyclophosphamide, rabbit anti-human thymocyte globulin, and TBI followed by infusion of 2.6 x 10(6)/kg of CD34-positive BM and PBSC. Engraftment was confirmed by FISH analysis, and GVHD was not observed. On day 50, he relapsed and died despite three transfusions of donor lymphocytes without GVHD prophylaxis. CD34-positive cell selection for HLA-mismatched transplantation may prevent severe acute GVHD.
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PMID:Allogeneic bone marrow and peripheral stem cell transplantation from a haplo-identical mother and CD34 positive selection for CML. 886 62

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

Between June 1985 and May 1992, 94 consecutive patients with acute myeloid leukemia (AML = 28), acute lymphoblastic leukemia (ALL = 27) and chronic myelogenous leukemia (CML = 39), were transplanted using genotypically HLA-identical marrow donors. All were conditioned with cyclophosphamide (CY) plus 12 Gy fractionated TBI. Graft-versus-host disease (GVHD) prophylaxis consisted of cyclosporin A alone in nine patients and methotrexate-cyclosporin A in 85 patients. Forty-eight patients developed grades II-IV acute GVHD and 24 of 68 patients who survived at least 100 days developed chronic GVHD. The 5-year actuarial probability of survival, event-free survival and relapse were 41 +/- 5%, 37 +/- 5% and 37 +/- 6%, respectively. In multivariate analysis, an increased risk of leukemia relapse was associated with (1) absence of chronic GVHD (P = 0.017), (2) advanced disease at transplant (P = 0.034) and (3) diagnosis of AML (P = 0.047). Our results confirm that disease status at transplant and chronic GVHD are the more important risk factors associated with leukemia relapse, and suggest that CY-TBI has only a partial role in eradicating leukemia in AML.
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PMID:Prognostic factors affecting leukemia relapse after allogeneic BMT conditioned with cyclophosphamide and fractionated TBI. 887 23

A 44-year-old woman with Ph-positive CML was treated with TBI, splenic irradiation, Ara-C, and CY. She then received unmanipulated marrow cells from her HLA-identical brother. GVHD prophylaxis was FK506 and MTX. WBC counts reached 1000/microliter on day 28 when all metaphases of marrow cells showed 46XY. However, on day 42, 46XX was detected in two of 20 metaphases, and the percentage of cells with female karyotype subsequently increased. On day 519, all metaphases showed female karyotype. BCR-ABL mRNA and Philadelphia chromosome were never detected throughout her post-transplant course. Fluorescence in situ hybridization (FISH) revealed complete recovery of host-derived hematopoiesis in the bone marrow, however, mixed T cell chimerism in the peripheral blood. This suggests that the persistence of donor-derived T cells may prevent disease recurrence through graft-versus-leukemia effect. The patient remains in a molecular complete remission with host-derived hematopoiesis 749 days post-transplant.
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PMID:Durable molecular remission in a patient with chronic myelogenous leukemia and host-derived hematopoiesis after allogeneic bone marrow transplantation. 889 99


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