Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0023418 (leukemia)
 93,477 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We analyzed the effects of T-cell depletion on the outcome of HLA-identical sibling bone marrow transplants for leukemia by comparing 731 T-cell-depleted transplants with 2,480 non-T-cell-depleted transplants. T-cell depletion decreased acute graft-versus-host disease (GVHD) (relative risk [RR] 0.45; P less than .0001) and chronic (GVHD) (RR 0.56; P less than .0001). However, it increased graft failure (RR 9.29; P less than .0001). Leukemia relapse also was increased. In first remission acute leukemia or chronic phase chronic myelogenous leukemia, leukemia relapse was 2.75 times more likely after T-cell-depleted transplants (P less than .0001). T-cell depletion increased the risk of treatment failure (RR 1.35; P less than .0003) and decreased leukemia-free survival. We also studied controllable variables associated with outcome of T-cell-depleted transplants. The unique findings were that among recipients of T-cell-depleted transplants for early leukemia, radiation doses greater than or equal to 11 Gy (RR 0.54; P less than .01), dose rates greater than 14 cGy/min (RR 0.56; P less than .002), and additional posttransplant immune suppression with cyclosporine alone (RR 0.53; P less than .0006) or cyclosporine plus methotrexate (RR 0.36; P less than .01) were associated with fewer treatment failures. Use of monoclonal antibodies rather than physical techniques for T-cell depletion (RR 2.01; P less than .03) and fractionated radiation (RR 1.69; P less than .05) were associated with increased treatment failure and lower leukemia-free survival. These data may be useful in designing strategies to improve results of T-cell-depleted transplants.
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PMID:T-cell depletion of HLA-identical transplants in leukemia. 191 89

One hundred and forty-six patients with acute leukaemia (81 with ANLL and 65 with ALL) received allogeneic bone marrow transplantation from their fully matched siblings. 121 patients underwent T-cell depletion (TCD) using Campath 1 monoclonal rat anti-human lymphocyte (CDw52) antibodies; 67 with Campath 1M and 54 with Campath 1G isotypes. Patients were conditioned for transplant using either total body irradiation combined with chemotherapy (125 patients) or busulfan and cyclophosphamide (21 patients). 112 recipients of T-cell depleted allografts received in addition total lymphoid irradiation (TLI) for prevention of rejection. Engraftment of neutrophils (> 0.5 x 10(9)/l) and platelets (> 25 x 10(9)/l) occurred on days 15 and 18, and on days 18 and 20 in recipients of Campath 1M and Campath 1G treated marrows respectively. Rejection was documented in 6.8% of T-cell depleted transplants. Leukaemia relapse-free survival at 2 years was 83% for patients transplanted in first CR, 76% in second CR (P2 = 0.34) and 42% in advanced leukaemia (P2 = 0.009). 81 marrow recipients, 38 with Campath 1M and 43 with Campath 1G treated marrow, received post-transplant graded increments of donor's peripheral blood lymphocytes (PBL) to induce graft-versus-leukaemia (GVL) effects. Administration of donor's PBL was associated with clinically significant GVHD and with decreased relapse rate especially in patients with ALL. Our data suggest that in patients receiving marrow allografts depleted of T cells by Campath 1 monoclonal antibodies, rejection can be reduced by adequate pregrafting immunosuppression. In patients with advanced disease, post-transplant cell-mediated immunotherapy (CMI) using donor's PBL may be beneficial; however, further studies are needed to define the optimal schedule of CMI for safe and effective prevention of relapse following TCD bone marrow transplantation in malignant haematological diseases.
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PMID:T-cell-depleted allogeneic bone marrow transplantation for acute leukaemia using Campath-1 antibodies and post-transplant administration of donor's peripheral blood lymphocytes for prevention of relapse. 773 48

A 16-year-old girl with refractory AML received unmanipulated BMT from an unrelated donor. Leukemia relapse occurred 82 days later. The patient was then treated with IL-2 1.8 x 10(6) U/m2 for 5 days per week and 2.5 MU/m2 IFN-alpha three times per week. Toxicities included fever, skin rash, somnolence and a generalized seizure. Treatment was stopped after 2 weeks. Acute GVHD developed at the end of therapy and the patient's leukemia went into remission. She died of fungal pneumonia 30 days later. We conclude that a combination of cytokines may be useful in treating relapsed leukemia after BMT.
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PMID:Treatment of leukemia relapse after bone marrow transplantation with interferon-alpha and interleukin 2. 777 25

We report 12 years' experience with histocompatible, related donor marrow transplantation for 123 patients with acute lymphoblastic leukaemia; 104 > or = second remission. Four regimens were studied: cyclophosphamide (Cy)-+total body irradiation (TBI) (n = 35); Cy+fractionated TBI (n = 45); TBI+high-dose cytarabine (n = 15); and hyperfractionated TBI+Cy (n = 28). 45 patients survive (34 +/- 9%; 95% confidence interval) between 1 and 12.7 years (median 7.8 years) following BMT and 29 +/- 8% survive leukaemia-free. Significantly improved disease-free survival was observed in patients with an initial WBC < 50 x 10(9)/l (P = 0.02). Conditioning regimens tested yielded similar outcomes, though TBI/cytarabine led to greater treatment-associated mortality. Leukaemia relapse was the most frequent cause of failure in 56 +/- 11%; median time of relapse 8 months following BMT, none beyond 2.2 years. Relapse was more frequent with higher WBC, shorter initial remission and previous CNS leukaemia. Acute and/or chronic GVHD was associated with a strong trend (P = 0.06) towards less relapse. Allogeneic BMT may be curative for a substantial fraction of patients with ALL, but additional anti-leukaemic measures beyond these conditioning modifications tested will be required to prevent post-transplant leukaemia recurrence.
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PMID:Allogeneic bone marrow transplantation for acute lymphoblastic leukaemia: risk factors and clinical outcome. 801 50

Forty-five patients with untreated, de novo acute myeloid leukemia (AML) were treated with high-dose cytosine arabinoside (Ara-C) plus mitoxantrone or daunorubicin. Forty-two patients entered complete remission with recovery of normal blood counts. Seven of these patients were excluded from further analysis (two, early consolidation chemotherapy; four, early relapse; one, hypersplenism). Of the remaining 35 patients, 20 (57%) developed thrombocytopenia and anemia (with or without neutropenia) a median of 3 weeks after entering complete remission. Post-remission cytopenias were more common in patients receiving mitoxantrone (81%) compared to those receiving daunorubicin (37%; p < 0.003). The cytopenias lasted a median of 54 days. Four of five patients in whom the cytopenias did not recover received mitoxantrone. Leukemia relapse or myelodysplasia did not explain these cytopenias. Post-remission cytopenias resulted in a greater than 90-day delay or prevention of planned autologous bone marrow transplantation in 13 of 17 otherwise eligible patients. We conclude that post-remission cytopenias are common following blood count recovery in AML patients entering complete remission with high-dose Ara-C and mitoxantrone or daunorubicin. Post-remission cytopenias do not necessarily imply leukemia relapse.
Leukemia 1994 Apr
PMID:Post-remission cytopenias following intense induction chemotherapy for acute myeloid leukemia. 815 48

Autologous bone marrow transplantation for leukemia was developed to extend the apparent curative potential of myeloablative therapy with allogeneic bone marrow transplantation to leukemia patients without histocompatible marrow donors. The conceptual problem with this approach is obvious: if the need for the transplant is based on overt or occult contamination of the marrow by leukemia, the use of autologous marrow seems destined to failure because of reinfusion of leukemia cells along with the harvested marrow. For this reason, ex vivo antileukemic treatment ("purging") of remission marrow was developed to justify autologous transplants for leukemia. Clinical trials involving thousands of patients worldwide have demonstrated curative potential of autologous bone marrow transplants, using purged or untreated remission marrow, for selected patients with acute myelogenous leukemia and acute lymphocytic leukemia. Purging appears to contribute to increased leukemia-free survival, at least in a subset of patients who are at very high risk of relapse, but this has not been tested in a prospective randomized trial and remains controversial. In acute myelogenous leukemia, in which the greatest experience exists, procedure-related mortality is much less for autologous than for allogeneic transplants; however, since leukemia relapse is much more frequent for autologous than for allogeneic transplants, the long-term disease-free survival is similar. In general, autologous transplants are preferred for older individuals and those without matched related donors, whereas allogeneic transplants are preferred for younger patients with matched related donors. Leukemia relapse has greatly limited the success of autologous transplants for acute lymphocytic leukemia. Autologous transplants for the chronic leukemias are in a much earlier stage of investigation. Autologous transplantation for leukemia is a fertile area for research. Important topics include conditioning regimens with improved antileukemic efficacy, the value of purging and the best method(s) for leukemia stem cell purging or normal stem cell selection, the possibility of inducing an autologous graft versus leukemia reaction, the use of immunomodulatory cytokines for postgrafting immune system manipulation, and the use of hematopoietic growth factors for ex vivo stem cell expansion and postgrafting support of marrow recovery.
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PMID:Autologous bone marrow transplantation for leukemia. 821 Dec 15

Chronic myeloid leukaemia (CML) can be treated successfully with allogeneic bone marrow transplantation (BMT) leading to long-term disease-free survival. Leukemia relapse, however, remains a significant clinical problem. Relapse following BMT presumably results from the expansion of small numbers of recipient leukaemic cells which have survived the conditioning therapy. In order to define patients who are at a high risk of leukaemia relapse, a variety of techniques have been employed to detect persistence of host haemopoiesis (mixed chimaerism, MC) or residual leukaemia (minimal residual disease, MRD). However, the precise relationship between the detection of MC and MRD post-BMT is unknown. We have investigated chimaerism and MRD status in 22 patients who were in clinical and haematological remission post-allogeneic BMT for chronic phase CML. Chimaerism was assessed using short tandem repeat PCR (STR-PCR) while BCR-ABL mRNA detection using reverse transcriptase polymerase chain reaction (RT-PCR) was performed to detect the presence of MRD. Seventeen patients received unmanipulated marrow (non-TCD) while in five patients a T cell-depleted transplant (TCD) was performed as additional GVHD prophylaxis. Chimaerism was evaluated in 18 patients (14 non-TCD, four TCD). Mixed chimaerism was an uncommon finding in recipients of unmanipulated BMT (21%) when compared to TCD BMT (100%). No evidence of MRD, as identified using the BCR-ABL mRNA RT-PCR assay, was detected in those patients who were donor chimaeras. Early and transient MC and MRD was detected in four patients (two non-TCD, two TCD) who have subsequently converted to a donor profile. One patient has stable low-level MC but remains MRD negative 4 years post-BMT. Late MC and MRD was observed in two patients who relapsed >6 years after TCD BMT for CML. We conclude that mixed chimaerism is a rare event in recipients of unmanipulated BMT and that donor chimaerism as detected by STR-PCR assay is consistent with disease-free survival and identifies patients with a low risk of leukaemic relapse post-BMT for CML.
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PMID:Persistent donor chimaerism is consistent with disease-free survival following BMT for chronic myeloid leukaemia. 925 92

Leukemia relapse is a major cause of treatment failure after allogeneic bone marrow transplantation. We administered recombinant interleukin-2 (rIL-2) to a patient who relapsed after unrelated allogeneic bone marrow transplantation (uBMT). While the number of peripheral blood monoblastic leukemia cells increased after administration of rIL-2, the patient achieved durable remission for 5 months after low-dose chemotherapy followed by adoptive transfer of engrafted graft-derived lymphokine-activated killer (LAK) cells. Following the disappearance of the blast cells, however, both cutaneous and liver GVHD were exacerbated. Administration of rIL-2 and adoptive transfer of graft-derived LAK cells are considered to be possible choices for the treatment of acute leukemia relapsing after uBMT when donor leukocyte transfusion is not available.
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PMID:IL-2/LAK therapy for refractory acute monoblastic leukemia relapsing after unrelated allogeneic bone marrow transplantation. 1019 6

Leukemia relapse is a major cause of treatment failure for patients with acute leukemia given allogeneic bone marrow transplantation (BMT). This study evaluated whether a reduction of the dosage of cyclosporine-A (Cs-A) used for graft versus host disease (GVHD) prophylaxis could reduce relapse rate (RR) in children with acute leukemia given BMT. Fifty-nine children who had transplantation from HLA-identical siblings were randomized to receive Cs-A intravenously at a dosage of 1 mg/kg/d (Cs-A1) or of 3 mg/kg/d (Cs-A3) until patients were able to tolerate oral intake. Subsequently, both groups received Cs-A orally at a dosage of 6 mg/kg/d, with discontinuation 5 months after BMT. The probability of developing grade II-IV acute GVHD was 57% for the Cs-A1 group versus 38% for the Cs-A3 group (P =.06); the probability of developing chronic GVHD was 30% for the Cs-A1 group and 26% for the Cs-A3 group (P = NS). Three patients died of grade IV acute GVHD: 2 were in the Cs-A1 and the third in the Cs-A3 group. The RR was 15% for the Cs-A1 group and 41% for the Cs-A3 group (P =.034); 1-year transplant-related mortality estimates were 17% and 7%, respectively (P = NS). With a median observation time of 44 months from BMT, the 5-year event-free survival for children belonging to Cs-A1 and Cs-A3 groups was 70% and 51%, respectively (P =.15). Our data demonstrate that the use of low Cs-A doses is associated with a statistically significant reduction of leukemia relapse, probably due to an increased graft versus leukemia effect. (Blood. 2000;95:1572-1579)
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PMID:Graft versus host disease prophylaxis with low-dose cyclosporine-A reduces the risk of relapse in children with acute leukemia given HLA-identical sibling bone marrow transplantation: results of a randomized trial. 1068 10

Early studies in murine models and more recent clinical data in heavily pretreated leukemia patients have shown that escalation of hematopoietic progenitor cells can overcome major genetic barriers and enable rapid and durable engraftment of haploidentical 3-loci mismatched transplants without graft-versus-host disease. In vitro studies suggest that veto cells within the progenitors population most likely mediate this facilitating effect. Leukemia relapse is relatively low in patients with acute myeloid leukemia (AML) but is greater in adults with acute lymphoblastic leukemia (ALL). Donor NK cells most likely mediate the resistance to relapse in patients with AML who are recipients of haploidentical transplants. Immune reconstitution in adults but not in children is slow as in adult recipients of HLA matched unrelated bone marrow transplants. The "mega dose" concept was also shown recently to be useful for tolerance induction in sublethally irradiated mice, so as to effectively overcome the marked resistance presented by the large number of lymphocytes surviving the sublethal conditioning. Thus, allogeneic chimeras generated by transplantation of large doses of Sca1+Lin- cells, permanently accept allogeneic donor type skin grafts. However, the numbers required to attain this desirable goal may not be easily collected from human donors. Nonalloreactive T cells synergize with murine Sca1+Lin- cells and might, therefore, enable achievement of engraftment of haploidentical transplants in sublethally conditioned patients.
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PMID:Transplantation tolerance induced by "mega dose" CD34+ cell transplants. 1070 67


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