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

Most children with acute lymphoblastic leukemia (ALL) are successfully treated by chemotherapy. For those patients, who relapse on therapy, bone marrow transplantation (BMT) is considered most appropriate after a subsequent remission is achieved. Three boys with ALL aged from 9 to 13 years met these criteria and received BMT from their HLA-compatible sisters after marrow ablation with total body irradiation 12 Gy plus high dose cytosine arabinoside 3 gm/m2/12h x 12 doses and graft-versus-host disease (GVHD) prophylaxis with cyclosporine plus short course methotrexate from March 10, 1989 to May 23, 1992. Filgrastim (rhG-CSF) was used to hasten the recovery of granulocyte in one patient. All three patients got full engraftment and two had grade 1 acute GVHD. None of them developed chronic GVHD. Two patients have disease-free survival over 51 and 12 months respectively post BMT without further chemotherapy. One patient died of recurrent refractory leukemia 5 months after BMT. The toxicity of this conditioning regimen included photophobia, conjunctivitis and erythematous skin rashes. One patient who received filgrastim from day 1 to 21 developed severe bone pain. However, this patient had faster recovery of granulocyte count than the other two patients. The preliminary results of this work favors BMT for children with recurrent ALL whose ultimate survival is usually poor when treated with chemotherapy. Further efforts are necessary to investigate new methods for reducing leukemic relapse in ALL patients undergoing BMT.
 ...
PMID:Allogeneic bone marrow transplantation for children with acute lymphoblastic leukemia in second remission or relapse. 783 80

Peripheral blood stem cells (PBSCs) have been used rarely for allogeneic transplantation because of concerns regarding graft failure and graft-versus-host disease (GVHD). We evaluated the results of allogeneic PBSC transplantation (allo-PBSCT) in 9 patients with refractory leukemia or lymphoma receiving myeloablative therapy followed by allo-PBSCT from an HLA-identical sibling donor. Three patients had relapsed 11 to 21 months after allogeneic bone marrow transplantation (allo-BMT) and underwent allo-PBSCT using the same donor. Six patients received PBSCs as their initial allogeneic transplant. Filgrastim-mobilized PBSCs were collected from the donors in 3 to 4 aphereses and cryopreserved. The apheresis collections contained a median nucleated cell count of 16.5 x 10(8)/kg (range, 10.8 to 28.7 x 10(8), 10.7 x 10(6) CD34+ cells/kg (range, 7.5 to 22.5 x 10(6)), and 300.0 x 10(6) CD3+ cells/kg (range, 127.8 to 1,523.2 x 10(6)). The median recovery of CD34+ progenitor cells after freezing, thawing, and washing was 106.4% (range, 36.7% to 132.0%). All patients received filgrastim posttransplant through engraftment, and cyclosporine and methylprednisolone were used for GVHD prophylaxis. Neutrophil recovery to greater than 0.5 x 10(9)/L and greater than 1.0 x 10(9)/L occurred at a median of 9 (range, 8 to 10) and 9 days (range, 8 to 11) posttransplant, respectively, which was similar to historical controls after allo-BMT and granulocyte colony-stimulating factor therapy. Platelets recovered to greater than 20 x 10(9)/L and greater than 50 x 10(9)/L at a median of 12 (range, 8 to 25) and 15 days (range, 11 to 59), respectively, which was significantly more rapid than for the controls (P < .01). Donor cell engraftment was documented by cytogenetics, fluorescence in situ hybridization, and/or restriction fragment length polymorphisms with longest follow-up of 283 + days. Three patients developed grade 2 acute GVHD involving only the skin. Three of five evaluable patients show limited chronic GVHD. Cryopreserved, filgrastim-stimulated allogeneic PBSCs may be a suitable alternative to allogeneic marrow for transplantation with the advantage of more rapid platelet recovery. Acute GVHD was minimal despite the infusion of 1 log more CD3 cells than with marrow allografts. Further studies are required to assess long-term risks of chronic GVHD.
 ...
PMID:Allogeneic blood stem cell transplantation for refractory leukemia and lymphoma: potential advantage of blood over marrow allografts. 760 19

Thirty adults with hematologic malignancies at high-risk for relapse were treated on a phase I-II study of high-dose thiotepa, busulfan (BU) and cyclophosphamide (CY) as the preparative regimen for allogeneic marrow transplantation. Cyclosporine and methylprednisolone or anti-CD5 ricin A chain immunoconjugate were used as graft-versus-host disease prophylaxis. Filgrastim was given from day 1 to enhance engraftment. Median follow-up time is 16 months (range 9-29 months). Grades III-IV regimen-related toxicity occurred in 5 (26%) of 19 patients treated with thiotepa 250 mg/m2 x 3, BU 1 mg/kg x 12 and CY 60 mg/kg x 2 and this was considered the maximal tolerated dose-schedule. Stomatitis and hepatoxicity were dose-limiting. All patients engrafted and had complete donor chimerism. The actuarial rate of acute graft-versus-host disease was 71% (95% CI 62-80%). The relapse rate at 1 year was 38% (95% CI 25-50%) and the actuarial survival at 1 year was 30% (95% CI 22-38%). The combination of thiotepa, BU and CY is tolerable as a preparative regimen for allogeneic marrow transplantation.
 ...
PMID:A phase I-II study of high-dose thiotepa, busulfan and cyclophosphamide as a preparative regimen for allogeneic marrow transplantation. 799 71

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.
 ...
PMID:[Transplantation of allogeneic peripheral hematopoietic progenitor cells instead of bone marrow]. 870 Dec 53

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.
 ...
PMID:The number of particular hematopoietic progenitors cells and the haematopoietic recovery following Allo PBSCT. 991 48

Unmodified allogeneic peripheral blood stem cell transplantation (alloPBSCT) was performed in 20 consecutive acute non-lymphoblastic leukemia (ANLL) patients from their HLA-identical siblings. There were 11 males and 9 females. Median age was 34 years (range 17-43). Donors were primed with 2.5-15 micrograms/kg/day s.c. granulocyte-colony stimulating factor (G-CSF, Neupogen, Roche). Conditioning regimen was Bu (16 mg/kg) + Cy (120 mg/kg) in 19 patients and high dose Ara-C (3 gr/m2 twice daily for 3 days) for one patient who relapsed after bone marrow transplantation. Eighteen patients were in CR1. CsA + short-term MTX (n = 19) or CsA alone (n = 1) were used for graft versus host disease (GVHD) prophylaxis. The median number of apheresis procedures for each patient was 2 (2-4). A median of 6.5 (3.2-38.2) x 10(8)/kg MNC or 9.4 (2.2-12.4) x 10(6)/kg CD34+ cells were given. Median days to reach granulocyte of > 0.5 x 10(9)/l and platelet of > 50 x 10(9)/l were 12 (10-14) and 15 (11-35) respectively. Day 100 transplant-related mortality was 20 per cent (4/20). Grade 2 to 4 AGVHD was seen in 8 out of 17 (47%) evaluable patients. Severe AGVHD occurred in 3 out of 17 (18%). Clinical CGVHD of all grades developed in 12 out of 17 (70%) evaluable patients. The mean disease-free survival and overall survival were 17 (range: 8-33 months) and 18 months (range: 10-34 months), respectively. In conclusion, alloPBSCT in ANLL is associated with a faster engraftment, no greater incidence of AGVHD, but increased risk of CGVHD.
 ...
PMID:Allogeneic peripheral blood stem cell transplantation in acute non-lymphoblastic leukemia. 1041 35

A study was done to compare treatment with Filgrastim (r-metHuG-CSF) given at three different times after unrelated bone marrow transplantation (BMT). Sixty-nine patients grafted with HLA-A, -B and -DR-compatible unrelated bone marrow were randomized to Filgrastim (5 microg/kg/day) starting on day 0 (n = 23), day +5 (n = 23) or day +10 (n = 23) after BMT. No significant differences were detected in hematological recovery, days with fever, days on antibiotics, incidence of bacteremia or need for erythrocyte, platelet and granulocyte transfusions between the three groups. Patients given Filgrastim starting on day 0, day +5 or day +10, respectively, reached an absolute neutrophil count (ANC) >0.5 x 109/l on a median of 17, 16 and 16 days after BMT. Starting Filgrastim treatment on day +10, rather than on day 0, reduced the costs of Filgrastim by $1060, with no significant change in the median number of days-to-hospital discharge in the three Filgrastim-treated groups. The incidences of acute and chronic GVHD, transplantation-related mortality, relapse, leukemia-free survival and patient survival (PS) were similar in all groups.
 ...
PMID:A prospective randomized trial of Filgrastim (r-metHuG-CSF) given at different times after unrelated bone marrow transplantation. 1051 92

To circumvent aGVHD in the early phase after allogeneic stem cell transplantation but to provide GVL activity later on, we performed alloPBSCT with CD34+ selected grafts followed by delayed add-back of CD3+ T cells. Ten consecutive patients having an HLA-identical sibling donor were enrolled on to this trial. Four patients were in first CR of high-risk ALL, another four in first CR of AML, one was in second myeloid blast crisis of CML, and one was in PR of relapsed NHL. Conditioning consisted of 2 x 60 mg/kg CY plus 12 Gy TBI. G-CSF (Filgrastim) mobilized peripheral cells were CD34+ selected using the Isolex 300i system in nine patients and the CliniMacs system in one. Median CD34+ purity was 86%. A median of 2.8 x 10(6)/kg CD34+ cells were transplanted. The number of CD3+ cells in the allografts was 5.7 x 10(4)/kg (median) after Isolex 300i, and 0.2 x 10(4)/kg after CliniMacs. All patients received G-CSF (Filgrastim) and engrafted rapidly. Standard-dose CsA was administered, and until day +60 no aGVHD occurred. At that time point, seven patients received 2 x 10(6)/kg CD3+ cells while CsA had been tapered to 50% of the starting dose. One of these patients died after a second T cell boost given on day +90 without concomitant immunosuppression due to grade IV intestinal aGVHD. Three others developed cutaneous cGVHD. Taken together, T cell depletion by CD34+ selection does not impair rapid engraftment in the HLA-identical sibling donor setting. Using standard-dose CsA the risk for acute GVHD seems to be minimized. Add-back of 2 x 10(6)/kg CD3+ cells on day +60 with CsA protection is feasible. However, whether this is the optimal time point and number of T cells remain to be further elucidated.
 ...
PMID:CD34 selected alloPBSCT and adoptive immunotherapy. 1093 76

Filgrastim (granulocyte colony-stimulating factor) has recently been reported to successfully treat patients with leukemic relapse after allogeneic peripheral stem cell transplantation (PSCT). However, the majority of the patients who responded also developed graft-versus-host disease (GVHD). Polyserositis as a manifestation of GVHD is a rare phenomenon. We report the first case of polyserositis following the use of filgrastim to treat a patient with acute myelogenous leukemia (M7), who had relapsed after an initially successful allogeneic PSCT. The polyserositis manifested with effusions and was initially controlled with high doses of steroids and pericardial stripping; however, after a quiescent period the patient eventually developed bronchiolitis obliterans with organizing pneumonia that required additional immunosuppressive therapy. We review the literature on GVHD-associated polyserositis and offer potential explanations for its pathogenesis.
 ...
PMID:Filgrastim treatment of acute myelogenous leukemia (M7) relapse after allogeneic peripheral stem cell transplantation resulting in both graft-versus-leukemia effect with cytogenetic remission and chronic graft-versus-host disease manifesting as polyserositis and subsequent bronchiolitis obliterans with organizing pneumonia. 1246 1

Based on our encouraging results of G-CSF-primed HLA-matched related marrow transplants for high-risk leukemia, we extended the study from matched related to haploidentical transplants using G-CSF primed marrow and sequential immunosuppressants to prevent both graft-versus-host disease (GVHD) and host-versus-graft rejection (HVGR). Fifteen high-risk leukemia patients, who needed urgent transplantation but lacked an HLA-matched donor, underwent G-CSF-primed haploidentical marrow transplantation without ex vivo T cell depletion. Donors were given G-CSF (Lenograstim) at 3-4 microg/kg/day for 7 days prior to marrow harvest. GVHD and HVGR prophylaxis were combined in the sequential usage of cyclosporin A, methotrexate, anti-thymocyte globulin and mycophenolate mofetil. All patients established sustained trilineage engraftment at a median of 19 days and 21 days for neutrophil and platelets respectively. G-CSF priming significantly increased CD34(+) and CFU-GM cells, reduced total lymphocytes and reversed the CD4(+)/CD8(+) ratio in the donor marrow. The incidence of grade II-IV acute GVHD was 33.3%. Nine patients survived more than a year with a Karnofsky performance status of 100%. Estimated overall disease-free survival at 2 years was 60 +/- 7%. In conclusion, using G-CSF priming marrow grafts along with sequential immunosuppressants provided an excellent alternative for the treatment of high-risk hematological malignancy in patients who lack matched donors.
 ...
PMID:G-CSF-primed haploidentical marrow transplantation without ex vivo T cell depletion: an excellent alternative for high-risk leukemia. 1247 77


1 2 Next >>