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)

Pluripotent stem cells of hematopoiesis and lymphopoiesis are among the CD34+ cells in blood or bone marrow. After granulocyte-colony stimulating factor (G-CSF) treatment, 1% to 2% of the mononuclear cells in blood are CD34+ cells, which can be procured by leukapheresis. We investigated the potential of CD34+ blood cells for reconstituting hematopoiesis and lymphopoiesis after allogeneic transplantation. HLA-identical sibling donors of 10 patients with hematologic malignancies were treated with G-CSF (filgrastim), 5 microgram/kg subcutaneously twice daily for 5 to 7 days. CD34+ cells were selected from the apheresis concentrates by immunoadsorption, concomitantly the number of T cells was reduced 100- to 1,000-fold. After transplantation, five patients received cyclosporine A for graft-versus-host disease (GvHD) prophylaxis (group I); five patients additionally received methotrexate (group II). G-CSF and erythropoietin were given to all patients. Mean numbers of 7.45 x 10(6) CD34+ and 1.2 x 10(6) CD3+ cells per kilogram were transplanted. In group I, the median times of neutrophil recovery to 100, 500, and 1,000 per mm3 were 10, 10, and 11 days, respectively. Group II patients reached these neutrophil levels after 10, 14, and 15 days, respectively. Platelet transfusions were administered for a median of 18 days in group I and 30 days in group II, and red blood cells for 9 and 12 days, respectively. Between day 30 and 60, lymphocytes reached levels of 353 +/- 269 cells per mm3. The median grades of acute GvHD were III in group I and I in group II. Two patients in group I died from acute GvHD. Two leukemic relapses occurred in group II. Complete and stable donor hematopoiesis was shown in all patients with a median follow up of 370 (45 to 481) days. Allogeneic blood CD34+ cells can successfully reconstitute hematopoiesis and lymphopoiesis. Reduction of T cells by CD34+ blood cell enrichment and cyclosporine A alone might not be sufficient for prophylaxis of severe acute GvHD.
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PMID:Transplantation of allogeneic CD34+ blood cells. 863 65

We evaluated patients presenting with large and recurrent sterile serosal effusions following bone marrow transplants. From a review of the Minnesota BMT Database from 1974 to 1993, seven patients with unexplained multiple effusions involving two or more of the pleural, pericardial or peritoneal cavities were identified. Patients with veno-occlusive disease (VOD), infections, cardiac insufficiency, tumor relapse and GM-CSF toxicity were excluded. All had onset following engraftment and six occurred before day 100. Unexplained multiple effusions were observed in recipients of allogeneic transplants but not autologous transplants and were found only in patients with acute and/or chronic GVHD. Five of seven patients also had cytomegalovirus (CMV) disease. Multiple effusions appear to be part of the presentation of severe acute or chronic GVHD, often in association with CMV disease in patients who receive allogeneic donor marrow.
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PMID:Unexplained effusions: association with allogeneic bone marrow transplantation and acute or chronic graft-versus-host disease. 1456

The role of recombinant human granulocyte colony-stimulating factor (rHuG-CSF) in myeloid recovery of children given an allogeneic bone marrow transplant (BMT) from an HLA-identical sibling for acute leukemia was evaluated in a retrospectively historically controlled study, involving 20 consecutive treated patients and 30 historical controls. In order to investigate the efficacy of rHuG-CSF in patients given a matched unrelated BMT with methotrexate as part of graft-versus-host disease (GVHD) prophylaxis, we also analyzed the kinetics of engraftment in eight further children with acute or chronic leukemia, transplanted using a volunteer donor. Patients were treated with 5 micrograms/kg/day of rHuG-CSF by 1-h intravenous infusion from day +5 until the absolute neutrophil count (ANC) was > or = 2 x 10(9)/l. No adverse effect related to treatment was observed in any patients. Children transplanted from an HLA-identical sibling and treated with rHuG-CSF reached an ANC count greater than 0.5 x 10(9)/l, 1 x 10(9)/l and of 2 x 10(9)/l in a significantly shorter time than the control group (day +9, +10 and +12, vs day +15, +22 and +29, respectively). An accelerated granulocyte production was also observed in patients receiving an unrelated transplant after a GVHD prophylaxis schedule including methotrexate, the median time to neutrophil recovery above 0.5 x 10(9)/l, 1 x 10(9)/l and 2 x 10(9)/l being +14, +15 and +17 days, respectively. In comparison to historical controls, all rHuG-CSF-treated patients had fewer days of fever, of antibiotic therapy and, only for children with HLA-compatible siblings, of hospitalization, whereas in the three groups the duration and severity of mucositis were comparable. No difference between the rHuG-CSF-treated patients and the historical controls given BMT from HLA-identical sibling was seen with regard to incidence of acute or chronic GVHD, relapse rate and actuarial event-free survival at day +100 and 1 year after transplantation. Our data suggest that in children given allogeneic BMT for acute or chronic leukemia, rHuG-CSF reduces duration of neutropenia, without increasing the rate of relapse or the incidence and severity of GVHD.
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PMID:Use of recombinant human granulocyte colony-stimulating factor in children given allogeneic bone marrow transplantation for acute or chronic leukemia. 867 51

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

We report the first experience of the use of GM-CSF as prophylaxis of ganciclovir induced severe bone marrow suppression in a CMV seropositive patient with acute myeloid leukemia who underwent a complete remission after an allogeneic bone marrow transplantation from an identical HLA sibling who also was CMV seropositive. A successful bone marrow engraftment was documented by day 14. Once peripheral blood counts stabilized, the patient received ganciclovir 5 mg/kg TIW. By day 73 severe neutropenia was documented but a spontaneous improvement occurred with discontinuation of ganciclovir. From day 100 to day. 110 he received daily ganciclovir at a dose of 5 mg/kg and the same dose of GM-CSF without signs of toxicity. There was no evidence of either acute graft versus host disease or of CMV infection. One year after transplantation he relapsed and died of complications of acute leukemia.
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PMID:[Prevention of myelotoxicity in a case of bone marrow transplantation using granulocyte-macrophage colony-stimulating factor along with ganciclovir]. 881 88

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

Treatment options for acute leukemia relapsing after allogeneic BMT include conventional chemotherapy or a second transplant; however, results are rather discouraging, the first option being associated with poor survival and the second with a high mortality rate. More recently, donor leukocyte infusion (DLI) from the original donor has been used for relapsed patients in an attempt to induce a graft-versus-leukemia (GVL) effect. This procedure is partially devoid of the toxicity inherent to a second BMT. At our Institution, a 36-year-old patient with biphenotypic AML in second complete remission after relapse following allogeneic BMT was treated with peripheral blood stem cell (PBSC)-enriched donor leukocytes, obtained after in vivo priming with rhG-CSF. The patient experienced extensive cGVHD but developed a testicular relapse while in full hematologic remission. After irradiation of the sanctuary site he remains free of disease, still with chronic GVHD, 21 months after bone marrow relapse. This case suggests that immunologically privileged sites are inaccessible to GVHD/GVL effect. This should be considered when planning salvage transplants procedures in patients at risk for extramedullary involvement.
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PMID:Testicular relapse of AML during chronic graft-versus-host disease induced by donor leukocyte infusion. 887 Mar 79

Successful allogeneic peripheral blood progenitor cell (PBPC) transplantation has recently been reported by several transplant centers. This is a first report describing allogeneic PBPC transplantation in five patients using related pediatric donors between the ages of 4 and 13 years. Donors underwent 3 or 4 days of rhG-CSF treatment (6 micrograms/kg q 12 h) for stem cell peripheralization prior to PBPC collection, which was performed by continuous-flow apheresis on day 4 or 5. Venous access was exclusively by ante-cubital veins. A median of 2.2 times (range 1.4-3.6) the donor's total blood volume (TBV) was processed per procedure. In cases where the donor's TBV was < 2 liters, the blood cell separator was primed with human serum albumin (HSA-5%), and anticoagulation was performed using a combination of heparin (pre-apheresis bolus + continuous infusion (CI)) and/or ACD-A (CI at a reduced rate). The median number of CD34+ cells collected per kg of donor body weight (b.w.) and per liter of donor blood processed during each procedure was 128 x 10(4) (range 58 x 10(4)-314 x 10(4)). Between one and two aphereses were sufficient to collect a safe CD34+ cell engraftment dose of 3 or 4 x 10(6)/kg of recipient b.w. Two PBPC recipients were parents, and three were siblings. After freezing and thawing, the median number of CD34+ cells per kg of recipient b.w. thawed and transfused was 8.5 x 10(6) (range 3.2 x 10(6)-9.7 x 10(6)). The time to PMN > 1000/microliters was between 10 and 16 days (four out of five evaluable patients), and platelets > 20000/microliters were reached between day 13 and 14 post-transplantation (three out of five evaluable patients). Two out of three evaluable patients developed grades one and three acute GVHD, and one out of three developed chronic GVHD. Two patients died of sepsis and VOD at day 10 and 19, respectively. Two adult patients are alive and in cytogenetic and molecular remission of CML at +339 and +227 days post-allotransplantation. One 3-year-old girl with hemophagocytic lymphohistiocytosis is in remission at +304 days post-transplantation. Using pediatric donors for allogeneic PBPC transplantation appears to be safe, yields a sufficient amount of progenitors for prompt engraftment, and results in clinical outcome similar to adult PBPC allotransplantation.
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PMID:Allogeneic peripheral blood stem cell transplantation using normal patient-related pediatric donors. 893 41

Dendritic cells (DC), as professional antigen-presenting cells, play a major role in stimulating naive T cell responses in vivo and in vitro, and may exacerbate or modulate T lymphocyte-mediated reactions, such as interactions between a hematopoietic graft and the recipient, eg GVHD and graft-versus-leukemia. Here, we describe a two-stage cell culture system for expansion of functionally active human DC from CD34+ marrow precursors. Optimal outgrowth was achieved by initially culturing CD34+ cells for 5 days in medium containing GM-CSF, MGF and TNF-alpha. Substitution of CD40L and IL-4 for TNF-alpha during a subsequent 5-day subculture increased DC content, such that by 10 days the cultures contained approximately 40% DC as determined by immunophenotype and morphology. An increase in DC purity to 84% at 10 days was achieved by immunomagnetic separation for CD1a+ cells from 5-day cultures and subculturing these cells in medium with IL-4 and CD40L. Reversing the sequence of growth factors during culture and subculture decreased the yield and purity of DC. Expression of CD80 and CD86 was enhanced by adding CD40L and IL-4, and the DC showed stimulatory activity in MLC. In conclusion, we have described a simple two-stage culture system to generate functional DC from CD34+ marrow precursors.
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PMID:In vitro expansion and characterization of dendritic cells derived from human bone marrow CD34+ cells. 893 57

Hematopoietic progenitor and stem cells are contained within the CD34+ cellular compartment of the bone marrow. Positively selected cytokine primed peripheral blood derived CD34+ cells have been shown to support autologous hematopoiesis after myeloablative therapy. We investigated hematologic reconstitution and incidence of graft-versus-host disease (GVHD) after transplantation of allogeneic peripheral blood CD34+ cells. CD34+ cells were selected from the peripheral blood of 10 matched related donors after treatment with rG-CSF followed by one to four apheresis procedures and biotin-avidin immune affinity purification. Ten patients with advanced hematologic malignancies were subsequently transplanted with cryopreserved allogeneic CD34+ cells after myeloablative chemotherapy. Immune affinity purification of CD34+ cells resulted in a 370-fold T cell reduction. Patients were grafted with a median number of 4.1 x 10(6) kg (1.6-6.4) CD34+ cells and 0.42 x 10(6)/kg (0.29-2.2) CD3+ cells. All patients received rG-CSF 5 micrograms/kg post-transplant and completely engrafted with neutrophils > 500/microliter after a median time of 10 days (9-15) and platelets > 20,000/microliter after 16 days (10-74). Complete donor chimerism was demonstrated by cytogenetic and molecular methods up to day +385 post-transplant. Cyclosporin A only was used for GVHD prophylaxis. Four of 10 patients developed acute GVHD with grade I (one) and II (three) which completely resolved with treatment. Two patients died from infectious complications. Three patients died from relapse or progressive disease. Five patients are alive in remission without GVHD with a median follow-up time of 254 (93-457) days and three of five are without immunosuppression. Allogeneic transplantation of positively selected peripheral blood-derived CD34+ cells is feasible and safe and leads to long-term engraftment without severe GVHD suggesting that peripheral blood-derived CD34+ cells contain pluripotent hematopoietic stem cells. The reduced number of T cells transplanted appears to be sufficient for engraftment.
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PMID:Allogeneic transplantation of positively selected peripheral blood CD34+ progenitor cells from matched related donors. 897 76


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