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)

Between July 1991 and January 1994, 52 patients with hematologic malignancies underwent BMT using BU/CY2 as conditioning regimen. Median patient age was 38 years. Eleven patients underwent autologous BMT, 22 HLA-identical allogeneic BMT, and 19 patients underwent a MUD or an allogeneic mismatched BMT. GVHD prophylaxis was with cyclosporine/methylprednisone in 26 patients; T cell depletion was used in 15 patients. VOD was observed in 7.5% of patients, IP in 12%, seizures in 4%. The overall incidence of grade II-IV acute GVHD was 35%. Delayed platelet engraftment was observed in seven of 11 patients who underwent autologous BMT. Graft failure was seen in seven of 19 (37%) patients who underwent MUD or allogeneic mismatched BMT. Six of the seven patients received T cell depletion as GVHD prophylaxis. BU/CY2 transplantation from an unrelated or family-mismatched donor with T cell depletion is associated with a high incidence of graft failure.
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PMID:Toxicity of busulfan and cyclophosphamide (BU/CY2) in patients with hematologic malignancies. 870 82

Twenty-five patients with hematologic malignancies were treated with busulfan (16 mg/kg) and cyclophosphamide (50 mg/kg x 3 days) as conditioning for bone marrow transplantation using marrow from serologically matched, DR locus genotypically identical unrelated donors. Previous studies of BuCy2 as conditioning for UD-BMT have reported a graft failure rate of up to 21% suggesting it may be insufficiently immunosuppressive in this setting. We elected not to use BuCy4 as it may have a higher incidence of extramedullary toxicity. In addition the patients received GM-CSF (500 mg/m2) from day 0, cyclosporine and short-course methotrexate (15 mg/m2 x 1, then 10 mg/m2 x 3) as GVHD prophylaxis and prophylactic ganciclovir at engraftment if either they or their donor were CMV antibody positive. The median age of the 25 patients was 41 years and the most common diagnosis was CML (76%). Seven patients were considered poor risk and eight males were recipients of marrow from female donors. Sixteen patients survive at a median of 435 days from transplant. The actuarial overall and disease-free survivals at 1 year in this group of older patients were 62 +/- 20% and 57 +/- 20% and 100-day survival was 70%. The engraftment rate was 100%; there have been no instances of secondary graft failure. Fifteen patients (60%) developed grade II-IV GVHD and 12 of 16 (75%) developed some chronic GVHD but only half of these were extensive. The performance status of survivors is good (median of 90); seven of 12 eligible patients are back at work. This study demonstrates that UD-BMT can be successfully performed in very closely HLA-matched older patients using a chemotherapy-only protocol and that low rates of severe acute GVHD can be achieved without T cell depletion.
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PMID:Unrelated donor bone marrow transplantation without T cell depletion using a chemotherapy only condition regimen. Low incidence of failed engraftment and severe acute GVHD. 872 53

To assess feasibility and potential advantages of PBSC allograft, we transplanted nine patients (age 20-47 years) with advanced or poor-risk hematologic malignancies. These included eight HLA-identical sibling transplants and one partially matched. Cells were collected from donors by apheresis after rh-G-CSF 10-16 micrograms/kg/day for 4-5 days, and stored at 4 degrees C until infusion. Patients were conditioned with busulfan 16 mg/kg and cyclophosphamide 200 mg/kg, and received GVHD prophylaxis with CSA-MTX. The graft consisted of PBSC alone, with a median of 101.2 (range 28-254.2) x 10(4)/kg CFU-GM, 6.84 (range 4.57-15.9) x 10(6)/kg CD34+ cells and 2.5 (range 1.2-6) x 10(8)/kg CD3+ cells. An ANC > 0.5 x 10(9)/1 occurred on (median) day 13 range 11-17), and a platelet count > 50 x 10(9)/l on (median) day 15 (range 12-29) post graft. One patient died of ARDS on day 13, the others are alive 96-485 (median 245) days from the graft. Two patients have relapsed, one of them with isolated CNS involvement. Acute GVHD (grade I-II) occurred in three patients and severe chronic GVHD in six patients, with no relationship to CSA withdrawal. This unexpected incidence of chronic GVHD might be linked to the high number of CD3+ cells in the graft, contributing to a favourable GVL effect.
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PMID:High incidence of chronic GVHD after primary allogeneic peripheral blood stem cell transplantation in patients with hematologic malignancies. 872 54

Twenty-six patients with haematological malignancy received cryopreserved but otherwise unmanipulated blood cell transplants (BCT) from five- or six-antigen matched siblings in whom progenitor cells had been mobilized by G-CSF. Outcomes were compared with a historical control group of 26 BMT patients matched for age and disease status. Granulocyte counts recovered to 0.5 x 10(9)/l in a median of 16 days after BCT compared with 21.5 days after BMT (P = 0.0002). Platelet counts, unsupported for 3 days, reached 20 x 10(9)/l in a median of 14 days vs 20.5 days (P = 0.0003) after BCT compared with BMT in those patients who engrafted. In the BCT and BMT groups, respectively, the risk of grade II-IV acute GVHD was 37 vs 21% (P = 0.16) and of chronic GVHD at 1 year 53 vs 48% (P = 0.9). There was no significant difference in red cell transfusions but BCT patients required fewer platelet transfusions (median 3 vs 5, P = 0.015) and fewer days in hospital (20.5 vs 25, P = 0.02). These results indicate that allogeneic BCT from matched and partially mismatched family donors result in faster engraftment than BMT without a significant increase in GVHD. Allogeneic BCT may prove to be a more tolerable procedure than BMT for both donor and recipient and there are indications of improved cost-effectiveness.
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PMID:Allogeneic blood cell transplants for haematological malignancy: preliminary comparison of outcomes with bone marrow transplantation. 873 85

Interleukin 2 (IL-2) stimulates the proliferation of T-cells both in vitro and in vivo. When murine or human peripheral blood (PB) or bone marrow (BM) mononuclear cells are incubated with IL-2 in vitro for 24 hours, cytotoxic T-cells are generated. If these activated cells are infused into mice, the enhanced cytotoxicity continues if low dose IL-2 is administered. This combination of administering activated cells with the subsequent low dose IL-2 infusion results in enhanced tumor cell destruction and improved survival rates in mice with acute myeloid leukemia. The encouraging results of these laboratory experiments prompted the initiation of phase I clinical trials in patients with refractory/relapsed hematologic malignancies and patients with breast cancer (Stages II-IV). Results from these trials demonstrate that stem cell transplantation with IL-2 activated stem cells (either PB or BM) with or without parenteral administration of IL-2 results in hematopoietic reconstitution with mild-to-moderate toxicities. This regimen also generates cutaneous and visceral autologous graft versus host disease (AuGVHD). The majority of our patients with relapsed/refractory hematologic malignancies or breast cancer developed either clinical and/or histological evidence of AuGVHD. Further studies are being conducted to determine if patients who develop AuGVHD experience improved disease-free survival from a possible autologous graft versus tumor (GVT) effect. Current laboratory evaluations include the elucidation of the pathogenesis of AuGVHD and molecular evaluation of the purging efficacy of IL-2.
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PMID:Stem cell transplantation with chemoradiotherapy myeloablation and interleukin-2. 874 4

The validity of biochemical indices routinely used for nutritional assessment was evaluated in patients undergoing allogeneic bone marrow transplantation for hematologic malignancies. Sixteen patients received total parenteral nutrition (TPN) for 15 days (35 kcal kg.body wt-1.day-1; 1.4 g amino acid.kg body wt-1.day-1) starting 1 day after transplantation. Nutritional status was evaluated before and after the TPN period by determining anthropometric (body weight, triceps skinfold thickness, and midarm circumference) and biochemical (transferrin, prealbumin, ceruloplasmin, and C3c) indices. Anthropometric indices, which were within the normal range before TPN, were not changed on day 15; transferrin and prealbumin concentrations significantly (p = 0.03) decreased whereas ceruloplasmin and C3c significantly (p = 0.03) increased. The levels of acute-phase proteins (alpha-1-acid glycoprotein, alpha-1-antitrypsin, and C-reactive protein), determined in 8 of the 16 patients at the same time intervals, were increased after 15 days of TPN and were significantly inversely correlated with transferrin and prealbumin. On the basis of these data, it appears that biochemical indices are not sufficiently reliable in the nutritional assessment of bone marrow transplantation patients because the levels of these substances are markedly affected by the acute-phase response secondary to febrile episodes and graft-versus-host disease, which frequently complicate transplantation.
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PMID:Biochemical indices may not accurately reflect changes in nutritional status after allogeneic bone marrow transplantation. 874 94

Sixty-five patients with haematological malignancy received high-dose chemotherapy or chemoradiotherapy followed by a T replete, HLA-identical sibling bone marrow transplant. All were scheduled to receive a standard cyclosporine/methotrexate immune suppressive regimen to minimise the risk of graft-versus-host disease post-transplant. Forty-six patients received all four scheduled doses of methotrexate, while in nineteen the day 11 dose was omitted due to marked oropharyngeal mucositis or febrile neutropenia. There was a slight increase in the incidence of acute graft-versus-host disease (GVHD) grades I-IV in those not receiving compared to those receiving day 11 methotrexate (84 vs 71% (P = 0.04)). However, there was no difference in the incidence of acute GVHD grades II-IV (14 vs 22%), in the incidence of chronic GVHD (38 vs 47%), in transplant-related mortality (21 vs 24%), in relapse rate (42 vs 51%), in 4-year survival (38 vs 48%), or in disease-free survival (38 vs 42%). These findings suggest that the day 11 methotrexate dose could be omitted without a major deleterious effect on the outcome of HLA-identical sibling marrow transplantation.
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PMID:Omission of day 11 methotrexate does not appear to influence the incidence of moderate to severe acute graft-versus-host disease, chronic graft-versus-host disease, relapse rate or survival after HLA-identical sibling bone marrow transplantation. 875 Feb 65

We retrospectively reviewed all positive Pneumocystis carinii findings among adult patients who had received an allogeneic BM transplant at the Helsinki University Central Hospital between July 1990 and December 1993. The aim was to define the incidence of late onset Pneumocystis carinii pneumonia (PCP) in BMT patients who had routinely received PCP prophylaxis for 6 months post-BMT. In 110 BMT patients, 16 episodes of PCP were documented. Only one patient had been receiving PCP prophylaxis at the onset of PCP. Fourteen of the episodes occurred more than 6 months post-BMT. (median 10.5, range 4-42 months); three of them beyond 1 year. All three had extensive chronic GVHD. Of the 11 patients with an onset between 7-12 months post-BMT, all but one were on methylpredisolone because of chronic GVHD (n = 7) or cytopenia (n = 2) and five of them were in relapse of their hematological malignancy. No mortality from PCP was detected. The risk of developing PCP between 7-12 months post-BMT among patients at risk was 13.4%. We conclude that PCP prophylaxis should be continued until 1 year post-BMT in patients receiving corticosteroid treatment as well as in those with a hematological relapse. Long-term prophylaxis beyond 1 year should be considered in cases with extensive chronic GVHD.
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PMID:Late onset Pneumocystis carinii pneumonia following allogeneic bone marrow transplantation. 880 14

The results of 33 allogeneic peripheral blood progenitor cells transplants (allo-PBPCT) in adult patients with hematologic malignancies were analyzed in a retrospective and multicenter study. In 21 of 33 cases (63%) the disease was refractory or in advanced stage and eight of the 33 cases (24%) were second transplants after relapse. Donors were treated with a median of 10 (4-16) micrograms/kg/day of rhG-CSF subcutaneously for 5-7 days. Three required a central venous line for harvesting. Peripheral blood leukapheresis product contained a median of 5.9 (1.8-13) 10(6)/kg CD34+ cells and a median of 309.5 (153-690) 10(6)/kg CD3+ cells. After a myeloablative regimen, all patients received PBPC from HLA-identical donors as the sole source of progenitor cells. Cyclosporin A (CsA) alone (n = 2), CsA and steroids (n = 9), and CsA and methotrexate (MTX) (n = 22) were used for GVHD prophylaxis. Growth factors post-transplant were given to 11 patients (33%). The median follow-up of the patients was 3 months. Actuarial median day for hemopoietic recovery was: neutrophils to >0.5 (>1) x 10(9)/l, day 14 (15); platelets to >20 (>50) x 10(9)/l, day 14 (21). The quantity of CD34+ cells infused did not significantly affect the engraftment kinetics, from a starting cutoff of 2.5 x 10(6)/kg. The speed of neutrophil recovery seemed to be influenced strongly by using rhG-CSF post-transplant and marginally by the type of GVHD prophylaxis. Actuarial probability for grade II-IV acute GVHD of the whole group was 37% (95% Cl, 20-54%).
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PMID:Allogeneic peripheral blood progenitor cell transplantation: analysis of short-term engraftment and acute GVHD incidence in 33 cases. allo-PBPCT Spanish Group. 883 93

Transfusion requirements of 477 patients with hematologic malignancies undergoing BMT from HLA-identical siblings were studied. The median (range) number of red cells transfused in the first, second and third months were 4 (0-32), 1 (0-39), and 0 (0-22) respectively, and the number of random donor platelet concentrates 32.5 (0-196), 0 (0-220) and 0 (0-135). On multivariate analysis, diagnosis other than acute leukemia, conditioning regimen other than cyclophosphamide-TBI, cyclosporine-methotrexate GVHD prophylaxis, and occurrence of acute GVHD increased platelet requirements significantly in the first month. Diagnosis other than acute leukemia, donor-recipient ABO incompatibility, conditioning regimen other than cyclophosphamide-TBI, and age over 18 years increased red cell requirements significantly in the first month. Platelet requirements in the second month and red cell requirements in the second and third months were increased significantly by the occurrence of acute GVHD, a diagnosis other than acute leukemia, and a conditioning regimen other than cyclophosphamide-TBI. Platelet requirements in the third month were influenced only by acute GVHD. We conclude that ABO incompatibility does not influence platelet requirements after allogeneic BMT. It affects red cell requirements in the first month along with the diagnosis, conditioning regimen, and age. However, other factors outweigh the influence of ABO-incompatibility on red cell requirements beyond the first month.
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PMID:Transfusion requirements after bone marrow transplantation from HLA-identical siblings: effects of donor-recipient ABO incompatibility. 883 8


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