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)

In a pilot study we tested the feasibility and safety of peripheral blood precursor cells instead of bone marrow cells for allogeneic transplantation. 13 patients, 7 male and 6 female between 24 and 52 years of age with hematological malignancies (10 with acute leukemias, 3 with myeloproliferative syndromes-were conditioned for bone marrow transplantation with VP-16, cyclophosphamide and total body irradiation followed by graft-versus-host disease prophylaxis with cyclosporin and methotrexate. Precursor cells were mobilized in the donors by granulocyte colony stimulating factor (G-CSF, Neupogen) 10 micrograms/kg s.c. from day-5 on. A total of 14.05 x 10(8) nucleated cells/kg recipient body weight (range 9.52-20.23 x 10(8)/kg), corresponding 6.82 x 10(6)/kg CD 34+ cells (range 1.43-15.84 x 10(8)/kg) or 113.9 x 10(4) CFU/kg (range 45.15-431.64 x 10(4)/kg) were collected by 3 phereses (1 patient 5 phereses) of 27-45 liters and infused without further manipulation. All patients engrafted with a recovery of total white blood cell count > 1 x 10(9)/l on day 15 (day 10-26) and of platelets > 20 x 10(9)/l on day +18 (day 12-39). 11 of the 12 patients developed aGvHD, 8 with grade II, 3 with grade > or = II. 9 of 13 patients are alive and well +4 to +16 months posttransplant, 3 patients died of aGvHD, one of veno-occlusive disease. These preliminary results confirm the capacity of peripheral blood precursor cells for rapid and complete engraftment in the allogeneic setting. Whether they induce more or equal aGvHD is an open question. Their value in allogeneic transplantation is currently under investigation in prospective randomized trials.
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PMID:[Transplantation of allogeneic peripheral hematopoietic progenitor cells instead of bone marrow]. 870 Dec 53

Six patients with high risk haematological malignancies received peripheral blood progenitor cells (PBPC) from unrelated donors. Four patients received PBPC as primary treatment and 2 following graft failure. Five donors were HLA-A, -B and -DR identical and one had a one antigen mismatch. PBPC were mobilised by treatment with G-CSF for 4-6 days. The patients received a range of 3.4 to 11.4 x 10(8) mononuclear cells/kg and 1.0 to 15.0 x 10(6) CD34 positive cells/kg. Four patients were given Campath 1G and 2 ATG prior to transplantation. The patient with one antigen mismatch received in vitro T-cell depleted PBPC using Campath 1M. All received cyclosporin and 5 in addition methotrexate. All recipients were given G-CSF and all engrafted. The patients developed no or mild acute GVHD. Two patients had limited chronic GVHD of the skin. The recipient of the mismatched graft died from extensive chronic GVHD. Three patients have had a relapse and two are alive and free of leukaemia.
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PMID:Transplantation of peripheral blood progenitor cells from unrelated donors. 872 40

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

The use of mobilized peripheral blood stem cells (PBSC) for hematopoietic reconstitution following myeloablative chemoradiotherapy has been well shown to be an effective and probably superior alternative to autologous bone marrow support. Early concerns of increased engraftment failure risk (owing to a decreased number of multipotential stem cells), increased graft vs. host disease risk (due to an excess of circulating T cells) and donor safety concerns, however, delayed efforts to use mobilized PBSC for allogeneic transplantation. Recent reports, however, have demonstrated excellent donor tolerance of G-CSF administration and yields of CD34+ progenitor cell collections. Engraftment with allogeneic peripheral blood stem cells has been rapid and sustained in several early clinical series. Surprisingly, no apparent increase in risk of moderate to severe acute graft versus host disease has occurred with unmanipulated mobilized PBSC. Despite this early promise, long-term safety concerns of administration of recombinant myeloid growth factors to normal donors have been raised. Long-term lymphohematopoietic engraftment also needs to be more conclusively demonstrated. Optimal mobilizing and collecting strategies also need to be defined to ensure donor safety and comfort. The possible roles of PBSC in the matched unrelated donor and mismatched related donor settings need to be defined before widespread adoption of mobilized PBSC as an alternative to bone marrow for allogeneic transplantation. Prospective randomized trials are recommended to definitively evaluate long term donor safety and recipient hematopoietic and immunologic reconstitution.
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PMID:Allogeneic peripheral blood stem cell transplantation. 874 5

The published experience of allogeneic bone marrow transplantation for primary myelofibrosis (PMF) is limited. Three patients (24-49 years) with PMF received allogeneic marrow grafts from HLA-identical sibling donors after conditioning with 110 mg/m2 melphalan and 1050 cGy total-body irradiation (TBI). Donor marrow was not depleted of T cells, and graft-versus-host disease (GVHD) prophylaxis comprised cyclosporine and methotrexate. None of the patients was splenectomized prior to the transplant. Two patients received G-CSF post-transplant to hasten neutrophil recovery. One patient died of multi-organ failure 23 days post-transplant. Hematopoietic recovery was relatively slow in the other two who had gradual resolution of the marrow fibrosis over several months. One of the two died of overwhelming pneumococcal sepsis within 2 weeks of stopping prophylactic penicillin 31 months post-transplant. The other patient is alive and well 20 months post-transplant with a Karnofsky score of 100% and no fibrosis of the marrow. We conclude that PMF is correctable by allogeneic BMT. Hematologic recovery post-transplant is slow, but counts may normalize with time without the need for splenectomy.
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PMID:Allogeneic bone marrow transplantation for primary myelofibrosis. 875 Feb 63

Allogenic peripheral blood stem cells (PBSC) were used for graft failure after BMT in two patients. These PBSC were mobilized by G-CSF in the same donors, harvested and given without reconditioning to the patients. In one patient, PBSC with a very high T cell number were given unprocessed, in the other patient, CD34+ cells were positively enriched due to a 2-antigen difference. None of the patients had hyperacute GVHD. Trilineage engraftment was seen after 13 days. Acute GVHD grade II to III developed on days +31 in patient 1 and +16 in patient 2, involving predominantly gut and liver, but sparing the skin. Thus, allogeneic PBSCT for graft failure did not cause hyperacute GVHD even with very high T cell numbers in patient 1, and graft failure with CD34 selected PBSC was successfully reversed even with a low number of T cells in patient 2.
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PMID:Allogenic peripheral blood stem cell (PBSC) transplantation in two patients with graft failure. 875 Feb 79

Six patients with high-risk leukaemia received a myeloablative regimen followed by allogeneic peripheral blood progenitor cells transplantation (PBPCT) from an HLA-identical sibling donor. Donors received 10-12 mu g/kg/day of G-CSF subcutaneously for 5 days. G-CSF was well tolerated except for moderate bone pain. Peripheral blood leukapheresis product contained 1-4 times more CD34+ cells and approximately a log more of T lymphocytes than marrow grafts from normal donors. In the two first cases the leukapheresis product was partially depleted of T-lymphocytes using counterflow centrifugation. No growth-factors were administered post-transplant. GVHD prophylaxis consisted of cyclosporin A (CyA) in one case, and CyA and methotrexate in five cases. All patients engrafted with a neutrophil count reaching more than 0.5 x 10(9)/L by day 12 to 21 post-transplant and a platelet count above 20 x 10(9)/L by day 6 to 41 post-transplant. Acute GVHD was clinical grade 0 (n = 2), I (n = 1), II (n = I), grade III (n = I) and grade IV (n = 1). One case presents an extensive chronic cutaneous GVHD and is currently being treated with methylprednisolone. In conclusion, allogeneic transplants using PBPC can be performed safely. This may result in a rapid neutrophil and platelet engraftment, without an apparent increased risk of GVHD.
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PMID:Allogenic transplants with peripheral blood progenitor cells: a report of six cases. 883 5

Allogeneic transplantation of selected CD34+ cells, rather than conventional transplantation of bone marrow (BM) harvest or peripheral blood (PB) leukapheresis products, has the advantage of reducing volume, facilitating storage and decreasing the amount of dimethylsulfoxide (DMSO) and cell lysis products, as well as reducing the number of T-lymphocytes responsible for graft-versus-host disease (GVHD). Using biotinavidin immunoaffinity columns (Ceprate SC system, CellPro; Bothell, WA), CD34+ cells were selected from each of 20 allografts (12 G-CSF-mobilized PB and 8 BM) collected from 14 HLA-identical normal healthy donors for transplantation. After the clinical-scale selection, the median concentration of CD34+ cells was 44.6% (range, 13% to 91%) in BM and 50.4% (range, 15% to 77%) in PB. Whereas 75% of the PB allografts had a CD34+ cell yield of more than 65%, only 37.5% of the BM allografts achieved such a yield, p < 0.01. The number of T-lymphocytes in the selected CD34+ cell allografts was reduced by two to three logs from a median of 4.2 x 10(9) to 7.8 x 10(5) CD3+ cells. The enrichment in CD34+ cells was 240-fold (range, 24- to 382-fold) in PB versus only 34-fold (range, 14- to 108-fold) in BM. Also, the enrichment in clonogenic cells was significantly more in PB (median value of 38.6-fold) than in BM (median value of 19.2-fold) and more in allografts from younger (< 50 years old) rather than older (> or = 50 years old) adult donors. A correlation was found between the percentage of CD34 or CD3+ cells before and after selection (r = 0.58 or r = 0.60, respectively, p < 0.05). Selective enrichment of the colony forming units-granulocyte-macrophage (CFU-GM) was found in all 20 allografts. The progenitor cell recovery after freezing and thawing was similar in BM and PB allografts, with a mean of about 60% for the CFU-GM and BFU-E. In the same six donors, the CD34+ cell yield was significantly more in the PB after mobilization (median 78.5%, range 50% to 90%) than in the BM before mobilization (median 41.5%, range 25% to 87%), p < 0.01. Ten patients with hematologic malignancies have been allotransplanted with 14 of the 20 selected CD34+ cells either combined BM + PB (n = 4) or single (n = 6) grafts. Seven patients did not develop acute GVHD, and only two patients developed > or = grade II GVHD, one of whom developed only grade II GVHD that resolved after brief treatment with corticosteriods. Only one patient showed chronic GVHD (skin and liver). The low incidence and severity of GVHD seen in the present study (only 30%) could be due to the two- to three-log reduction of T-lymphocytes in the selected CD34+ cell allotransplants. All 10 patients had stable hematological recovery, and seven had full donor hematopoiesis. In conclusion, G-CSF-mobilized PB leukapheresis products undergoing selection of CD34+ cells have a greater yield and enrichment of progenitor cells than BM harvests collected from HLA-identical normal healthy donors for allogeneic transplantation. The low incidence and severity of both acute and chronic GVHD (30%) seen in the present study are very encouraging.
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PMID:Comparison between bone marrow and G-CSF-mobilized peripheral blood allografts undergoing clinical scale CD34+ cell selection. 884 43

There is increasing interest in blood cell transplants (BCT) from normal donors as an alternative to BMT. Ten patients with relapsed or persistent leukemia after BMT received intensive cytotoxic conditioning followed by allogeneic BCT. Three BCT were from single-antigen mismatched donors; two of the corresponding recipients had rejected a BMT from the same donor. Two patients received BCT from a different donor (one matched, one single-antigen mismatched). The other six BCT were from the same, fully matched, bone marrow donors. Donors were given G-CSF to mobilize progenitor cells which were collected by a single 2-4 h leukapheresis. Methotrexate, CsA and folinic acid were used for GVHD prophylaxis for all transplants but CsA was discontinued sooner after BCT than after BMT. One patient died without engraftment having rejected a BMT from the same single-antigen mismatched donor 4 years previously. Nine patients had granulocyte recovery at a median of 14 days, up to 6 days faster than with their previous BMT. Platelet recovery was also 2-6 days faster than with BMT in four previously engrafting patients. Four patients died without platelet recovery after BCT within a year of BMT, three of treatment-related toxicity and one of relapse. Two patients developed grade II acute GVHD. Of six patients given BCT more than a year from BMT, four, all with acute leukemia, survive 7, 14, 29 and 29 months after BCT and one relapsed at 7 months. All four survivors developed chronic GVHD. These results indicate that BCT may be useful therapy for relapse occurring more than a year after BMT.
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PMID:Second allogeneic transplants for leukemia using blood instead of bone marrow as a source of hemopoietic cells. 887 9


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