Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0018133 (graft-versus-host disease)
 18,032 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Recently, treatment of leukemia has shown remarkable progress. Development of new antileukemic drugs, improvements in supportive care and rapid progress in bone marrow transplantation have resulted in considerable changes in responses in refractory leukemia. Chemotherapy for Acute leukemia: By the introduction of Mitoxantrone and etoposide and a new combination chemotherapy including them, a high remission rate of acute leukemia is obtained, but because of the high relapse rate the 5-year survival rates in our center were 20% for adult ALL and 18% for ANL. In order to reduce the relapse rate, a new regimen containing intensive consolidation treatments is now being studied in a nation-wide cooperative study. BMT: In 1987, 160 BMTs including 75 acute leukemia and 28 CML, were registered in Japan. The improvements in the management of graft versus host disease (GVHD) and infections in the granulocytopenic period has contributed to the marked increase in the long-term survival rate after BMT. In our center the long-term survival rate rose from 20% before 1984 to 85% after 1985. Colony stimulating factor: Macrophage-colony stimulating factor (M-CSF) and granulocyte colony stimulating factor (G-CSF) were studied in Japan. In the double-blind placebo controlled study of M-CSF, a significantly shorter duration of granulocytopenia, as well as a significantly lower rate of failure of BMT (i.e., death or retransplant) was observed. In the phase II study of G-CSF, a rapid recovery of granulocytes after chemotherapy or BMT and marked efficacy on infection in granulocytopenic patients were observed.
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PMID:[Multidisciplinary treatment of leukemia]. 265 20

Advances in the treatment of childhood acute lymphoblastic leukemia (ALL) have been striking while results have been less impressive in adults who develop this disease. Obvious differences in a patient's ability to withstand cytotoxic therapy may account, in part, for these findings, but the biologic behaviour of the disease in the two age groups appears to be different; relapses are more frequent and cures less common in adults. In fact, age alone appears to be the most important prognostic factor in ALL. The demonstration of the efficacy of bone marrow transplantation in advanced disease as well as the marked improvements in supportive care and the development of effective high-dose cytotoxic preparative regimens, especially those which use total body irradiation, however, have paved the way for transplantation in first complete remission. Formerly, most adult ALL patients who underwent bone marrow transplant did so in relapse, or in second or subsequent remission. In most studies 40-50% of first remission adult patients attain long-term disease-free survival after allogeneic and autologous bone marrow transplant. Relapses are considerably higher in the autologous transplant group when compared to the allogeneic group, but the latter population may experience increased morbidity and mortality due to graft-versus-host disease and opportunistic infection. These differences may reflect the beneficial graft-versus-leukemia effect in the allograft as well as infusion of autologous leukemia cells in the autograft but neither transplant subtype appears superior. Compared to more conventional approaches, however, transplantation may offer improved disease-free survival, although patient selection appears to be significantly influence outcome. These many inherent biases must be noted when comparing markedly different approaches, e.g. transplant versus conventional therapy. The challenge of demonstrating which therapy is superior for adult ALL patients can only be addressed in a well-designed, prospective, randomized trial.
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PMID:Bone marrow transplantation for acute lymphoblastic leukemia (ALL). 785 Feb 67

In a retrospective multicentre study, we analyzed 184 consecutive patients who underwent bone marrow transplantation (BMT) from identical siblings for adult acute lymphoblastic leukemia in first complete remission between March 1980 and May 1989. The main causes of transplant-related mortality were GVHD and interstitial pneumonitis. Univariate and multivariate analyses identified the mode of total body irradiation (TBI) as the only independent predictive factor of transplant-related mortality. Ninety-one patients received single-dose TBI and 93 received fractionated-dose TBI as part of the conditioning regimen prior to BMT. Transplant-related mortality was more frequent in the single dose group (p = 0.017). The incidence of interstitial pneumonitis, acute and chronic GVHD and veno-occlusive disease of the liver was not statistically different between the two irradiation groups. However, fatal interstitial pneumonitis was significantly more frequent in the single dose irradiation group (p = 0.031). These results show that transplant-related mortality is closely associated with the mode of TBI administration. The increased relapse rate in the fractionated group explains why there was no difference between the two groups in terms of overall leukemia-free survival.
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PMID:Allogeneic bone marrow transplantation for adult acute lymphoblastic leukemia in first complete remission: factors predictive of transplant-related mortality and influence of total body irradiation modalities. 813 42

Over the past ten years considerable experience has been gained in autologous bone marrow transplantation (ABMT) for acute myelogenous leukemia and it is becoming possible to identify patients who may benefit from this approach. In acute lymphoblastic leukemia (ALL)the precise role of autologous transplantation particularly in first remission is much less clear than in AML. Formerly, most adult ALL patients who underwent ABMT did so in relapse or in second or subsequent remission. The fact that some of these patients could become long term survivors has encouraged the use of ABMT in first remission. In most studies 40-50% of first remission patients attained long term disease free survival (DFS). Relapse rates are considerably higher in patients receiving ABMT when compared to those receiving an allogeneic transplant, but the latter group of patients experience significant morbidity and mortality (15-30%) due to graft-versus-host disease and opportunistic infections. ABMT clearly has the potential to effect cures in ALL patients and its role and timing are now the subject of major clinical studies. As the mortality of ABMT for ALL rapidly decreases to approximately 5%, more widespread use of such a procedure may replace the protracted maintenance chemotherapy usually given in this disease.
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PMID:[Autologous transplantation in acute lymphoblastic leukemia in adults]. 1049 83

We analyzed the outcome of 108 adult acute lymphoblastic leukemia patients undergoing allogeneic bone marrow transplantation (BMT). Philadelphia (Ph) chromosome occurred in 35.2% patients at diagnosis. Two-thirds of patients received allogeneic BMT in first complete remission (CR1) BMT. Salvage BMT was performed in 21 and 16 patients at second complete remission (CR2) and beyond CR2. Donors were human leukocyte antigen-identical siblings in 87 patients, and match-unrelated donors in 21 patients. Conditioning contained total body irradiation (TBI) in 92.6% patients. Overall survival (OS) for BMT at CR1 and BMT beyond CR1 were 46.2 and 20.3% at 15 years. Multivariate analyses (including age, sex, disease status, donor type, acute graft-versus-host disease (aGVHD), stem cell source, cytogenetics, grade 1/2 aGVHD and TBI-containing conditioning regimen) identified age<35, BMT at CR1 and grade 1/2 aGVHD as favorable factors for OS. Disease-free survival (DFS) for BMT at CR1 and beyond CR1 were 45.8 and 15.9% at 15 years, respectively, with BMT at CR1, age<35 and grade 1/2 aGVHD being favorable factors for DFS. Importantly, conventional adverse risk factors such as the Ph chromosome, B-cell phenotype and high leukocyte count were not associated with inferior survivals. In summary, the adverse impact of Ph chromosome, B-cell phenotype and high leukocyte count was overcome by allogeneic BMT. Matched unrelated donor transplantation appears promising.
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PMID:Long-term results of allogeneic bone marrow transplantation for 108 adult patients with acute lymphoblastic leukemia: favorable outcome with BMT at first remission and HLA-matched unrelated donor. 1757 12

We retrospectively evaluated the outcomes of 37 adult patients with acute lymphoblastic leukemia (ALL) undergoing allogeneic hematopoietic stem cell transplantation (allo-SCT) conditioned with medium-dose VP-16 (VP, 30 mg/kg), cyclophosphamide (CY, 120 mg/kg), and fractionated total-body irradiation (TBI, 12 Gy) (medium-dose VP/CY/TBI). The median age of the patients was 26 years. Thirteen patients underwent transplantation from HLA-matched related donors (MRD), 18 patients underwent transplantation from HLA-matched unrelated donors (MUD), and 6 patients underwent transplantation from HLA-mismatched donors (MMD). Thirty-two patients received bone marrow and 4 patients received peripheral blood stem cells. Ten patients were Philadelphia chromosome-positive (Ph(+)) and 35 patients were in complete remission (CR) at transplantation. All of the patients achieved engraftment, and grade 3 organ toxicity before engraftment occurred in 27 patients. Grade II-III acute graft-versus-host disease (GVHD) and chronic GVHD (cGVHD) occurred in 15 and 18 patients, respectively. No patient developed grade IV acute GVHD (aGVHD) or died of GVHD. At median follow-up of 35.1 months, 32 patients were alive and all Ph(+) patients were alive. Three patients died of relapse and 2 died of transplant-related mortality (TRM). The actuarial 3-year overall survival (OS) rate, relapse rate, and TRM rate were 89.2%, 8.1%, and 5.4%, respectively. Non-CR at transplantation, MRD, and no aGVHD were significant adverse prognostic factors for survival. Medium-dose VP/CY/TBI for adult ALL patients was associated with lower relapse rate and no increase in toxicity, resulting in better survival.
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PMID:Excellent outcome of allogeneic hematopoietic stem cell transplantation using a conditioning regimen with medium-dose VP-16, cyclophosphamide and total-body irradiation for adult patients with acute lymphoblastic leukemia. 1841 Aug 99

We present 60 patients with refractory (n=8) or relapsed (n=52) adult ALL who received allogeneic hematopoietic SCT (HSCT) with (n=41) or without (n=19) prior reinduction chemotherapy. In our center, omission of reinduction is recommended if a suitable donor is promptly available, tumor burden is moderate and disease features suggest a highly aggressive course. Overall survival (OS) of the whole cohort at 1, 2 and 5 years was 42, 33 and 28%, respectively. Leukemia-free survival at 1, 2 and 5 years was 37, 33 and 24%. Deaths were due to relapse (n=25), acute or chronic GVHD (n=7), infections (n=8) or toxicity (n=4). Interestingly, patients who did not receive reinduction before HSCT had better outcomes than patients who received reinduction with OS at 1, 2 and 5 years being 58 vs 34%, 47 vs 25% and 47 vs 18%, respectively (P=0.039). Importantly, even achievement of a second CR after reinduction was not associated with improved survival compared to patients directly proceeding to HSCT. We conclude that patients who undergo HSCT for refractory or relapsed ALL can achieve long-term survival. In selected patients, reinduction chemotherapy can be omitted if immediate HSCT is feasible.
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PMID:Allogeneic SCT in refractory or relapsed adult ALL is effective without prior reinduction chemotherapy. 1871 50

Twenty-two adult acute lymphoblastic leukemia (ALL) patients (21 of 22 in complete remission [CR]) received reduced-intensity conditioning followed by allogeneic transplantation. All patients were high risk. After a uniform preparative regimen (fludarabine 40 mg/m(2) x 5, cyclophosphamide 50 mg/kg, 200 cGy total body irradiation), patients received either matched related (n=4) or umbilical cord (n=18) donor grafts. All patients reached neutrophil engraftment and 100% donor chimerism (median, days 10 and 23, respectively). Overall survival, treatment-related mortality (TRM) and relapse were 50% (95% confidence interval [CI], 27%-73%), 27% (95% CI, 9%-45%), and 36% (95% CI, 14%-58%) at 3 years, respectively. There were no relapses beyond 2 years. The cumulative incidence of acute and chronic graft-versus-host disease was 55% and 45%. Hematopoietic cell transplantation in CR1 (n=14) led to significantly less TRM (8%, P< .04) and improved overall survival (81%, P< .01). For adults with ALL in CR, reduced intensity conditioning allografting results in modest TRM, limited risk of relapse, and promising leukemia-free survival. Clinical trial numbers are NCT00365287, NCT00305682, and NCT00303719.
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PMID:Prolonged survival in adults with acute lymphoblastic leukemia after reduced-intensity conditioning with cord blood or sibling donor transplantation. 1917 1

We examined the efficacy of reduced-intensity conditioning (RIC) and compared outcomes of 93 patients older than 16 years after RIC with 1428 patients receiving full-intensity conditioning for allografts using sibling and unrelated donors for Philadelphia-negative acute lymphoblastic leukemia (ALL) in first or second complete remission. RIC conditioning included busulfan 9 mg/kg or less (27), melphalan 150 mg/m(2) or less (23), low-dose total body irradiation (TBI; 36), and others (7). The RIC group was older (median 45 vs 28 years, P < .001) and more received peripheral blood grafts (73% vs 43%, P < .001) but had similar other prognostic factors. The RIC versus full-intensity conditioning groups had slightly, but not significantly, less acute grade II-IV graft-versus-host disease (39% vs 46%) and chronic graft-versus-host disease (34% vs 42%), yet similar transplantation-related mortality. RIC led to slightly more relapse (35% vs 26%, P = .08) yet similar age-adjusted survival (38% vs 43%, P = .39). Multivariate analysis showed that conditioning intensity did not affect transplantation-related mortality (P = .92) or relapse risk (P = .14). Multivariate analysis demonstrated significantly improved overall survival with: Karnofsky performance status more than 80, first complete remission, lower white blood count, well-matched unrelated or sibling donors, transplantation since 2001, age younger than 30 years, and conditioning with TBI, but no independent impact of conditioning intensity. RIC merits further investigation in prospective trials of adult ALL.
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PMID:The outcome of full-intensity and reduced-intensity conditioning matched sibling or unrelated donor transplantation in adults with Philadelphia chromosome-negative acute lymphoblastic leukemia in first and second complete remission. 2040 37

Molecular mechanisms involved in TBI preconditioning before allogenetic transplantation remain unclear. To elucidate possible signaling pathway in it, gene expression profiles of peripheral lymphocytes were compared between samples 24h after each 4.5 Gy total body irradiation treatment (total 9 Gy) from 4 adult ALL patients. 478 significant expressed genes and three unique patterns were identified. Of these, a dominant progressively repressed expression of genes involved in ubiquitin-dependent process and repressed expression only at 9 Gy of genes involved in allograft rejection and graft-versus-host disease pathways were observed. The results suggest these pathways may play important roles for subsequent transplantation.
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PMID:Gene expression signature of lymphocyte in acute lymphoblastic leukemia patients immediately after total body irradiation. 2124 31


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