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)

Blood cell transplantation (BCT) is now common practice in the autologous setting. We performed a pilot study of allogeneic BCT, collected after the priming of an HLA-identical sibling with a glycosylated rhu-G-CSF (lenograstim) (10 microg/kg). Fifty-four patients were included (38 +/- 11; M/F = 33/21; CML (n = 17), AML (n = 14), ALL (n = 15); MDS (n = 8)). Transplant procedures were standard (TBI regimen = 47 (87%); MTX-CsA: n = 37; CsA-PDN: n = 17). No serious adverse events were reported in donors. A median of 11 (3.5-29.1) x 10(6)/kg CD34+ cells, 332 (33-820) x 10(6)/kg CD3+ cells were collected. Four patients did not engraft (early death: n = 2; graft failure: n = 2). Fifty-one patients initially recovered 0.5 x 10(9)/l ANC and 25 x 10(9)/l platelets at 15 (10-30) and 13 (9-188) days. 29/51 and 29/38 experienced grade > or =2 acute and chronic GVHD. With a median follow-up of 25 months (18-36), relapse rate is 16% +/- 8, survival and DFS probabilities are similar (50% +/- 13). A better outcome is documented for patients under 45 years and in the early phase of the disease (n = 28), with an identical survival and DFS of 71% +/- 13. In conclusion, lenograstim is a potent rhu-G-CSF for mobilisation of allogeneic hematopoietic progenitors. Two-year follow-up indicates good haematological recovery but some concerns about graft failure and chronic GVHD have arisen deserving prospective evaluation.
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PMID:Mobilisation of healthy donors with lenograstim and transplantation of HLA-genoidentical blood progenitors in 54 patients with hematological malignancies: a pilot study. 1045 58

Allogeneic peripheral blood progenitor cell (PBPC) transplants are an alternative to BMT, although G-CSF mobilization dose, timing of pheresis and risk of GVHD are not well defined. We compared harvest characteristics, donor and recipient outcomes and costs of two PBPC transplant strategies with historical controls who received BMT. Twenty donors mobilized with four daily s.c. G-CSF doses (5 microg/kg/day) (group 1) and 20 mobilized with 10 microg/kg/day G-CSF (group 2) were compared with 20 BM controls (group 3). G-CSF and phereses were well tolerated. Four of 40 PBPC donors required femoral catheter placement. At least 2.5 x 10(6) CD34+/kg recipient weight were collected with two phereses in 19/20 donors (group 1) and 18/20 donors (group 2). Time to neutrophil (18 vs 20 vs 22 days, P = 0.02) and platelet (21 vs 24 vs 27 days, P = 0.005) engraftment was shorter in the PBPC groups (group 2 vs group 1 vs group 3) but secondary engraftment outcomes were not different. The incidence of grade 2-4 aGVHD was higher in the low-dose G-CSF group (group 1) but there was no difference in cGVHD, 100-day or 1-year survival. The mean PBPC transplant cost (group 1) at first hospital discharge was less than BM (group 3) ($34,643 vs $37,354) but the mean overall cost for both groups was similar at 100 days ($46,334 vs $46,083). Allogeneic PBPC transplant with short course, low-dose G-CSF mobilization is safe, feasible and cost equivalent to allogeneic BMT.
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PMID:Clinical and economic analysis of allogeneic peripheral blood progenitor cell transplants: a Canadian perspective. 989 24

13 patients have been transplanted at Institute of Hematology and Blood Transfusion since 1995 using allogeneic PBPC either alone or with bone marrow as a source of progenitor cells. All donors were G-CSF mobilised HLA identical family members. PBPC harvests were performed on D 4,5, (6) of G-CSF administration. The medium content of TNC, CD34+, CD3+, CD4+and CD8+cells/kg b.w. of the recipients in the grafts were: 13,1x10(8)(TNC), 11,4x10(6)(CD34+), 393x10(6)(CD3+) 243x10(6)(CD4+), 125x10(6)(CD8+) The patients received either BuCy2 or CyTBI preparative regimen and Cyclosporin A + short course of Methotrexate for GVHD prophylaxis. Engraftment of ANC >500 was achieved by D+16 and PLT >20.000 by D+19. Three of ten evaluable patients developed acute and three of nine chronic GVHD. 8 patients survive with the longest follow up 776 days.
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PMID:Transplantation of allogeneic peripheral blood progenitor cells--a single centre experience. 991 42

AlloPBSC-T is rapidly replacing bone marrow transplantation. The minimum number of progenitor cells required for rapid engraftment following PBSCT is unknown. 12 patients underwent alloPBSC-T during treatment for haematological malignancy. PBSC's were mobilised with Filgrastim (10microg/kg/day sc). The mobilisation was monitored daily by the number of mononuclear cells (MNC) and CD34+ cells in peripheral blood. Collections were normally performed on days 4 and 5, by means of apheresis (Fenwall CS 3000+). No further manipulation of PBSC was performed. A median of 10.15x10(8)/kg MNC (range 5.87-12.24), 9.075x10(6)/kg CD34+ (range 0.78-18.98), 53.85x10(4)/kg CFU-G (range 17.2-138.4), 28.05x10(4)/kg CFU-M (range 4.1-102.2), 115.65x10(4)/kg BFU-E (range 9.1-255.2), 3.65x10(4)/kg CFU-GEMM (range 0.3-10.4) were infused into recipients following BuCyl20 conditioning. Haematopoietic reconstitution was observed in 11 patients. The median number of days to achieve a neutrophil count of 0.5x10(9)/l was 16 (range 12-20), the platelet count of 20x10(9)/l was 12 (range 8-20) and RBC transfusion independence was 11 (range 8-20). 9 recipients developed acute GVHD (3 grade I0, 2 grade II0, 1 grade III0, 3 grade IV0). We found that the number of MNC in PBSC had no influence on the number of progenitors. All the patients who received G-CFU>20x10(4)/kg, BFU-E>60x10(4)/kg and CFU-GEMM>1x10(4)/kg experienced a rapid haematopoietic recovery. No relation was found between the number of reinfused progenitors and the appearance of GVHD.
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PMID:The number of particular hematopoietic progenitors cells and the haematopoietic recovery following Allo PBSCT. 991 48

Between February 1995 and August 1997, 11 children (eight males, three females) aged 4-16 years (median 7 years) underwent allogeneic PBPC transplantation for treatment of hematological disorders. Seven patients with acute leukemia (n = 5 ALL, n = 1 AML) or lymphoma (n = 1) received primary allogeneic PBPC transplantation, four patients received a second allotransplantation for graft failure (n = 1 AML, n = 1 sickle cell anemia) or disease recurrence (n = 1 ALL, n = 1 MDS). Five donors were HLA-identical siblings, five were 0-1 antigen mismatched family members and one was a matched unrelated donor. Donors received G-CSF 10-12 microg/kg/day for 3-7 days, and underwent one or two leukaphereses. The median cell yield per donor expressed per kg of recipient body weight was as follows: mononucleated cells 10.8 x 10(8)/kg (range 4.7-21.2); CD34+ cells 8.6 x 10(6)/kg (range 3.2-22); CD3+ cells 3.7 x 10(8)/kg (range 2.7-7.5). All patients achieved an ANC >0.5 x 10(9)/l after a median of 12 days (11-18). An unsupported platelet count >50 x 10(9)/l was reached 15 days (13-21) after PBPC transplantation; four patients failed to reach this threshold. Acute GVHD (aGVHD) grades II to IV occurred in eight (73%) patients: seven of them experienced grade III-IV aGVHD. Seven patients evaluable for chronic GVHD (cGVHD) were scored as absent in five, limited in one and extensive in one patient. As of September 1997, six patients (55 %) were alive between 60 and 938 days post-transplant (median follow-up 274 days); four patients with malignancy were alive in CR after primary allotransplantation, two patients were alive after a second PBPC transplant. Five patients have died with the main causes of death being aGVHD (n = 3), ARDS (n = 1), relapse of the underlying disease (n = 1). In conclusion, despite the limited number of patients, these preliminary results indicate that PBPC may be considered as an alternative to bone marrow for allografting also in children.
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PMID:Allogeneic transplantation of peripheral blood progenitor cells in children: experience of two pediatric centers. 998 87

Eleven patients with hematologic malignancies and two with aplastic anemia were treated using unmanipulated marrow and immunoselected CD34+ blood cells. Donors began G-CSF (10 microg/kg) injections 1 day after undergoing bone marrow harvest. Blood stem cells were collected on day 5 of G-CSF. Peripheral blood lymphocytes were depleted via CD34-positive selection. If, after marrow and blood harvest, less than 2.0 x 10(6) CD34 cells/kg were mobilized, leukapheresis was repeated on day 6. Median time to an absolute neutrophil count greater than 500 microl was day 10; transfusion-independent platelet count greater than 20,000/microl was day 13; average hospital discharge was day 14; and average inpatient hospital charges were 101,870 US dollars. Acute GVHD grade II occurred in five of 13 patients. No patient developed grade III or IV acute GVHD. At a median follow-up of 10 months, no patient has developed extensive chronic GVHD. Allografts of unmanipulated bone marrow supplemented with G-CSF-mobilized and CD34 immunoselected blood cells may prevent an increased risk of GVHD while preserving the rapid engraftment kinetics of peripheral blood. Supplementation of marrow with CD34 enriched blood cells appears to result in rapid engraftment, early hospital discharge, lower inpatient charges, decreased regimen-related toxicity, and no apparent increase in GVHD.
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PMID:Stem cell component therapy: supplementation of unmanipulated marrow with CD34 enriched peripheral blood stem cells. 1010 May 82

Many patients have not been offered potentially curative allogeneic marrow transplants because of the toxicity of myeloablative regimens in the setting of advanced age or organ dysfunction. We treated five patients, ineligible for myeloablative chemotherapy due to one of these criteria, with fludarabine-based non-myeloablative chemotherapy followed by reinfusion of G-CSF-mobilised allogeneic peripheral blood progenitor cells (PBPC). Two patients died early of multi-organ failure. Another patient with massive splenomegaly was infused with a suboptimal number of PBPC; no engraftment was documented. The remaining two patients demonstrated mixed chimerism early post-transplant, but by 3 and 6 months respectively, engraftment was almost entirely of donor origin. One of these patients, transplanted with relapsed AML, remains in remission with extensive chronic GVHD at 17 months. The other patient, transplanted with chemorefractory mantle cell lymphoma, progressed early post-transplant but entered remission coincident with the onset of severe GVHD following cessation of cyclosporin A, suggesting a powerful graft-versus-mantle cell lymphoma effect. These preliminary observations suggest this approach results in engraftment and GVHD/graft-versus-tumour effects similar to myeloablative regimens and may provide an alternative in patients ineligible for conventional conditioning regimens.
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PMID:Fludarabine-based non-myeloablative chemotherapy followed by infusion of HLA-identical stem cells for relapsed leukaemia and lymphoma. 1019 93

To determine whether administration of G-CSF induces phenotypic or functional changes in T cells, we examined peripheral blood T cells from normal individuals receiving G-CSF for activation antigen and adhesion molecule expression before and after G-CSF administration. G-CSF (10 microg/kg/day) was administered subcutaneously to 14 normal individuals for 3-5 days and their PBMC were serially analyzed with monoclonal Ab (mAb) directed to HLA-DR, CD45RO, CD45RA, CD25, CD122, CD95, CD11a, CD49d, CD44 and CD62L (L-selectin) coupled with anti-CD3 mAb. Among T cells positive for these antigens, only the proportion of T cells expressing L-selectin significantly decreased from 68% to 37% after 3-day G-CSF administration. When peripheral blood CD3+ T cells obtained before and after G-CSF administration were sorted into two populations depending on the expression of L-selectin and tested for their proliferative response to allogeneic B cells, the reactivity of L-selectin- cells to alloantigen stimulation was consistently lower than that of L-selectin+ cells regardless of the exposure to G-CSF. The decrease in the relative number of L-selectin+ cells induced by G-CSF administration may contribute to the unexpectedly low incidence of severe acute GVHD after allogeneic PBSC transplantation.
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PMID:Administration of G-CSF to normal individuals diminishes L-selectin+ T cells in the peripheral blood that respond better to alloantigen stimulation than L-selectin- T cells. 1019 95

Ten patients with acute leukemia (AL) in early relapse after allo-BMT were treated with a modified MEC (mitoxantrone, etoposide and Ara-C) regimen followed by donor PBPC collected after mobilization with G-CSF. Seven patients achieved CR or had normal hemopoietic reconstitution: two had an early relapse at days +53 and +48, two patients died from acute GVHD at days +31 and +96, one died of interstitial pneumonia at day +55, and two patients experienced long-term survival. One patient with refractory disease and nodal involvement who did not respond to the first BMT had overt expansion of the leukemia at day +36; one patient with Ph+ ALL and one with ANLL evolving from MDS, both with skin involvement, had blast cells in peripheral blood at day +27 and +26, respectively. Transient cytopenia occurred in all patients; a normal granulocyte and platelet count was achieved within 3 weeks in all patients but one; acute GVHD occurred in six patients, and four had chronic GVHD. This approach is feasible in patients in early relapse after allo-BMT. It assists prompt re-establishment of normal donor hematopoiesis avoiding the prolonged cytopenia observed after donor lymphocyte infusion in AL patients relapsed after allo-BMT.
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PMID:Chemotherapy and donor peripheral blood progenitor cells for acute leukemia in early relapse after allogeneic bone marrow transplantation. 1021 92

Serum soluble interleukin-2 receptor - alpha (sIL-2R) levels markedly increased at the engraftment period in patients who underwent allogeneic bone marrow transplantation (BMT). Since serum G-CSF levels increased during G-CSF administration and decreased after the cessation, increased sIL-2R levels appeared to be induced by G-CSF administration. There was no increase in sIL-2R levels in a patient given macrophage colony-stimulating factor (M-CSF). The sIL-2R levels at the engraftment period and the onset of acute graft-versus-host disease (GVHD) were higher in patients who developed acute GVHD during G-CSF administration than in those who developed acute GVHD after G-CSF cessation. This finding suggests that G-CSF administration may possibly augment acute GVHD. However, it appears to be unlikely, because in the entire population, 18 of 35 patients had acute GVHD while only 6 of 17 patients had acute GVHD during G-CSF administration. Further analysis is still needed in order to draw definite conclusions. Preconditioning regimens did not appear to affect the sIL-2R levels, when the variable frequencies of methotrexate (MTX) administration were compared.
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PMID:Possible role of granulocyte colony-stimulating factor in increased serum soluble interleukin-2 receptor-alpha levels after allogeneic bone marrow transplantation. 1034 83


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