Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0023467 (acute myeloid leukemia)
 35,200 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Patients who relapse post-ABMT are usually resistant to conventional therapy, and a potentially curative therapy with allogeneic BMT is limited due to availability of a matched donor. To assess whether such patients can be salvaged using partially mismatched related donors (PMRD), eight patients age 6-50 years old underwent PMRD-BMT. All patients ALL (n = 3) and AML (n = 5) were in relapse 7-31 months after first BMT. Donors (1-3 Ag mismatch) were selected from family members. Conditioning included TBI, etoposide, Ara-C and cytoxan (n = 3), or busulfan, thiotepa, and etoposide (n = 5). GVHD prophylaxis consisted of partial T cell depletion followed by systemic immunosuppression. All evaluable patients established sustained engraftment by day 18. Severe regimen-related toxicity was evident in the gastrointestinal and hepatic systems (6/8 and 4/8, respectively), the latter associated with poor outcome (P < 0.014). Acute but not chronic GVHD, grade > or = II occurred in 3/7 patients. Four of eight patients are disease-free, maintaining longer remission than following their first BMT (14 vs 9 months). In conclusion, our data shows that PMRD-BMT is a feasible option for patients who relapse post-BMT and use of such alloreactive grafts may be appropriate earlier in the disease course of high risk patients.
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PMID:Partially mismatched related donor transplants as salvage therapy for patients with refractory leukemia who relapse post-BMT. 867 54

A patient with non-Hodgkin's lymphoma in remission developed a myelodysplastic syndrome (MDS) 12 years after ABMT. This patient had undergone bone marrow harvesting prior to any chemoradiotherapy. He had received the autograft following conditioning with high-dose CY and TBI. Chromosomal analysis of BM cells revealed complicated abnormalities. Similar karyotypic abnormalities in host-derived BM cells were found in another patient with AML who had received allogeneic BM following conditioning with CY plus TBI 15 months previously. These findings suggest that MDS or clonal karyotypic abnormalities following ABMT may derive from endogenous hematopoietic stem cells that survive the BMT preparative regimen.
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PMID:Hematopoietic clone with karyotypic abnormalities of host origin after bone marrow transplantation: two case reports. 870 2

Between May 1983 and March 1994, 31 patients with AML in second CR underwent BMT. Fifteen underwent allogeneic BMT from an HLA-identical sibling donor and 16 without a donor, unpurged ABMT. Two different preparative regimens were used: CY (120 mg/kg) and 12 Gy of fractioned TBI (19 patients), and Bu (16 mg/kg) and Cy (120 mg/kg) (BuCy2) in 12 patients. Main clinical characteristics including age, sex, length of first remission, FAB type, and number of leukocytes at diagnosis were similar in both groups. A combination of MTX and CsA was used in 13 cases whereas either CsA or MTX alone was employed in the other two patients. With a median follow-up of 5 years the actuarial 5 year probability of disease-free survival (DFS) for the whole group was 39.8% (95% CI: 29.5-50.1%). The 5 year DFS was equivalent for those who received either ABMT (41.6 +/- 14.2%) or allogeneic BMT (40 +/- 15%). Probabilities of relapse and non-relapse mortality for ABMT and allo BMT patients were 48.7 +/- 16.1 and 18.7 +/- 14.3, and 30.1 +/- 19.2 and 40.7 +/- 16.9, respectively. DFS was better in those patients with a longer duration of first CR (> 18 months) 62.5 +/- 14.4 vs 30.4 +/- 17.9%, attributable to a significantly lower relapse rate in this group of patients 16.6 +/- 12.8 vs 57.8 +/- 22.7 (P 0.05). In conclusion, similar results were observed when ABMT and allo BMT were compared for AML in CR2. A higher antileukemic effect associated with the allo BMT is balanced by an increase in transplant-related mortality. Duration of first remission was the most important factor affecting DFS and better outcome was observed for patients with longer CR1.
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PMID:Autologous or allogeneic bone marrow transplantation for acute myeloblastic leukemia in second complete remission. Importance of duration of first complete remission in final outcome. 880 3

We analyzed retrospectively data from 1696 patients with AML transplanted in Europe from January 1987 to December 1992 and reported to the acute leukemia EBMT registry. Groups of patients were analyzed according to age (adults and children) and status at transplant (first remission = CR1; second remission = CR2). (1) 1114 adult patients were transplanted in CR1; 516 received an allograft; 598 received an autograft. Following alloBMT, the transplant-related mortality (TRM) was significantly higher (27 vs 13%, P < 10(-4)), the relapse incidence (RI) lower (25 vs 52%, P < 10(-4)) and the leukemia-free survival (LFS) better (55 vs 42%, P = 0.006). Favorable prognostic factors for alloBMT were a FAB type other than M4-M5, a donor-recipient combination excluding a female donor to a male recipient, and a younger age. Favorable prognostic factors for ABMT were a younger age of the patients at time of transplant, the AML3 FAB type, and a longer interval from CR1 to ABMT. (2) 288 adult patients were transplanted in CR2: 98 received an allograft; 190 received an autograft. The TRM was higher following allogeneic BMT (32 vs 20%, P = 0.02) and the RI lower (42 vs 63%, P = 0.001). The LFS was not significantly different (alloBMT: 39%; ABMT: 30%, P = 0.22). (3) 242 children were transplanted in CR1; 129 received an allograft; 113 received an autograft. Following alloBMT, the RI was lower (25 + 5 vs 48 + 6%, P < 10(-4)), and the LFS better (68 vs 47%, P = 0.002). The use of TBI was a favorable prognostic factor in allografted patients with a lower RI and a better LFS. (4) The number of children transplanted in CR2 was too small for a comparative analysis. These results confirm that both allogeneic and autologous BMT are suitable curative approaches for AML. They favor the use of an HLA identical related allogeneic transplant when available, especially in younger patients, over ABMT with unpurged marrow. The role of purging in ABMT could not be addressed in this study.
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PMID:Retrospective evaluation of autologous bone marrow transplantation vs allogeneic bone marrow transplantation from an HLA identical related donor in acute myelocytic leukemia. A study of the European Cooperative Group for Blood and Marrow Transplantation (EBMT). 883 3

Forty-four adults with AML (n = 18) or ALL (n = 26) beyond first remission underwent unpurged (n = 39) or purged (n = 5) autografting after 110-140 mg/m2 melphalan and 1050 cGy TBI. ALL patients were eligible to receive maintenance chemotherapy with 6-mercaptopurine and methotrexate for 2 years after hematologic recovery. The duration of first remission was 1-167 months (median 11). The median time to 50 x 10(9)/I platelets was 76 days, and that to 0.5 x 10(9)/I neutrophils 31 days. Eight patients died of transplant-related toxicity; seven within 1 year. Twenty-two patients relapsed at 1-20 months (median 2.5 months). The 3-year probabilities (95% CI) of relapse and disease-free survival are 58% (43-75%) and 31% (17-45%), respectively. The duration of the first remission (< 1 year vs > or = 1 year) and the stage of transplant (second remission vs other) had no effect on relapse or disease-free survival. There was a trend towards higher relapse rates (76 vs 34%) and poorer disease-free survival (19 vs 49%) among ALL patients compared with AML which did not reach significant levels due to small patient numbers. We conclude that melphalan-TBI is a suitable conditioning regimen for autografting in advanced leukemia. The outcome of AML patients is comparable to standard regimens, but the outcome of ALL patients is poor and measures to enhance the anti-leukemic efficacy are necessary.
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PMID:Melphalan-total body irradiation and autologous bone marrow transplantation for adult acute leukemia beyond first remission. 883 4

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

Eighty-five patients (median age 28 years) with acute myeloid leukemia (AML) in first remission underwent allogeneic bone marrow transplantation (BMT) from HLA-identical siblings between 1978 and 1987 after cyclophosphamide and single-fraction total body irradiation with cyclosporine for graft-versus-host disease (GVHD) prophylaxis. The actuarial probabilities of development of acute and chronic GVHD were 57% and 47%, respectively. Twenty-six patients died of transplant-related complications at a median of 3.5 months, and two of unrelated causes. Seventeen patients relapsed at a median of 6.5 months. Forty patients were alive and well at 74-197 months (median 157) after BMT; seven (18%) with limited chronic GVHD requiring therapy. The actuarial 10-year probabilities of transplant-related death, relapse, and disease-free survival were 33%, 25% and 48% respectively. In multivariate analysis, infusion of a lower cell dose, development of GVHD, and age > 35 years were associated with increased transplant-related mortality, donor-recipient ABO incompatibility with a lower relapse rate, and age > 35 years and a lower cell dose with poorer disease-free survival. We conclude that with long-term follow-up, allografting in AML after cyclophosphamide-TBI and cyclosporine has resulted in disease-free survival that is comparable to most currently reported series. Patients who are alive and well 3-4 years after BMT have excellent prospects of long-term survival.
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PMID:Long-term follow-up of patients undergoing allogeneic bone marrow transplantation for acute myeloid leukemia in first complete remission after cyclophosphamide-total body irradiation and cyclosporine. 889 89

In the present single institution study of 66 leukaemia patients (28 AML, 23 ALL, 15 CML), the factors influencing haematological recovery after allogeneic bone marrow transplantation (alloBMT) were analysed retrospectively in order to identify the optimal conditions required for a rapid haematological recovery after alloBMT. All patients received GVHD prophylaxis with cyclosporine A plus methotrexate. The mean number of days required to achieve > or = 0.5 x 109/l neutrophil count after alloBMT was 17 (median 17, range 9 to 27 days) and 19 patients (28.8%) had rapid neutrophil recovery within 15 days after alloBMT. The haematological recovery was more rapid in the 38 patients without GVHD or with only grade I GVHD. Furthermore, 50% and 40% of patients receiving 10 (n = 18) or 5 (n = 20) micrograms/kg/day G-CSF had rapid neutrophil recovery within 15 days after alloBMT, versus only 7.1% of patients not receiving G-CSF post-transplant (n = 28), p < 0.001. The neutrophil recovery was similar in patients receiving either fresh or cryopreserved allografts and either TBI-containing or busulfan-containing conditioning regimen. A significant correlation was found between neutrophil recovery and either the MNC or CFU-GM content of the allografts, r = 0.33, p < 0.01. The mean number of days required for neutrophil recovery was only 16 days (median 16, range 9 to 24 days) in patients receiving allografts containing > 1 x 10(5) CFU-GM/kg (n = 28) versus 19 days (median 19, range 13 to 27 days) in patients receiving allografts containing < 1 x 10(5) CFU-GM/kg (n = 35). Three patients receiving allografts containing less than 0.5 x 10(5) CFU-GM/kg had primary neutrophil engraftment failure. The mean number of days required to achieve 20 x 109/l platelet count was 21 (median 20, range 11 to 50 days) and 30 patients (46.9%) had platelet recovery within 20 days after alloBMT. The platelet recovery after alloBMT was not significantly affected by the type of leukaemia, conditioning regimen, or G-CSF administration. The mean number of days required for platelet recovery after alloBMT was only 20 days (median 18 days) in patients receiving allografts containing > 1.0 x 10(5) BFU-E/kg (n = 35) versus 23 days (median 20 days) in patients receiving allografts containing < 1.0 x 10(5) BFU-E/kg (n = 24). Seven patients receiving allografts containing less than 0.5 x 10(5) BFU-E/kg had primary platelet engraftment failure. The present study has identified the high number of progenitor cells in the allografts infused and the daily administration of G-CSF post-transplant as the optimal combination for a rapid neutrophil recovery after alloBMT. More significantly, the number of BFU-E in allografts was the most significant factor to determine platelet recovery after alloBMT. The development of GVHD of grade II or more during the first weeks after alloBMT was associated with slower haematological recovery and longer period of fever during neutropenia and hospitalisation.
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PMID:Factors influencing the haematological recovery after allogeneic bone marrow transplantation in leukaemia patients treated with methotrexate-containing GVHD prophylaxis: a single-centre experience. 906 85

We report the outcome of 50 consecutive patients with CR1 acute leukemia (AML = 22; ALL = 28) treated with autologous BMT, after cyclophosphamide and TBI, followed with a sequential high dose rIL2 regimen. rIL-2 (RU 49637 from Roussel-Uclaf, Romainville, France) was started after hematological reconstitution an average of 72 +/- 22 days post transplant. The schedule consisted of a continuous infusion over 5 cycles (Cycle 1: 5 days starting on day 1; cycle 2-5: 2 days starting on day 15, 29, 43 and 57). Patients were treated at 4 different dosages (12 (N = 40), 16 (N = 3), 20 (N = 2), 24 (N = 5) x 10(6) IU/m2/day). Toxicities were mainly related to capillary leak syndrome and thrombocytopenia. Patients received an average of 122 +/- 49 10(6) IU/m2. Two patients with AML died from toxicity. rIL-2 infusion was associated with very a high level of immune stimu-lation of both T-cells (P < 0.05) and natural killer (NK) cells (P < 0.05) and associated cytolytic functions (P < 0.05). With a minimal and median follow-up of 21 and 46 months, 3 year leukemia free survival is 41 +/- 6% overall, 39 +/- 10% and 43 +/- 8% for AML and ALL respectively. Relapse probabilities at 3 years are 59 +/- 11% for AML and 57 +/- 8% for ALL. We conclude that this short infusion of rIL-2 over 2 months, resulting in an increased immune stimulation, is not associated with a better leukemic control for patients with acute leukemia transplanted early after reaching first complete remission.
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PMID:The use of a sequential high dose recombinant interleukin 2 regimen after autologous bone marrow transplantation does not improve the disease free survival of patients with acute leukemia transplanted in first complete remission. 925 Aug 17


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