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)

To evaluate the efficacy and toxicity of two different etoposide (VP-16) dosages (30 or 45 mg/kg) in combination with busulfan/cyclophosphamide as conditioning therapy followed by stem cell transplantation in acute myeloid leukemia (AML), 90 patients with AML received either 30 mg/kg (n = 60) or 45 mg/kg (n = 30) etoposide in combination with busulfan (16 mg/kg) and cyclophosphamide (120 mg/kg). The stem cell source was allogeneic related bone marrow (BM) (n = 53), allogeneic unrelated BM (n = 5), allogeneic unrelated peripheral blood (PBSC) (n = 2), syngeneic BM (n = 2), autologous BM purged (n = 9) or unpurged (n = 9), autologous PBSC (n = 10). Fifty-six patients (62%) were in first CR, 26 (29%) were > first CR, and eight (9%) were transplanted in relapse. Principal toxicities in both groups were mucositis and hepatotoxicity. Forty-five mg/kg etoposide resulted in greater hepatic toxicity (P = 0.03), and a higher incidence of VOD (23 vs 12%, P = 0.04) and acute GVHD grade III/IV (13 vs 5%, NS). The treatment-related mortality was 17% in the 30 mg/kg group and 33% in the 45 mg/kg group, mainly due to infections, intestinal pneumonia and GVHD. Hematological recovery of leukocytes 1/nl was comparable in both groups (17 vs 16 days). After a median follow-up of 16 months 19% in the 30 mg/kg group and 23% in the 45 mg/kg group relapsed. In patients who had undergone allogeneic related bone marrow transplantation in first CR no relapses occurred after a median follow-up of 3 years. For all patients the 3-year estimated disease-free survival was 62% in the 30 mg/kg group and 40% in the 45 mg/kg group (P = 0.03). For patients in first CR who underwent allogeneic related stem cell transplantation the 3 year disease-free survivals were 80% and 66%, respectively (P = 0.4). We conclude that etoposide 30 mg/kg or 45 mg/kg in combination with busulfan/cyclophosphamide is a highly active regimen for bone marrow transplantation of patients with AML with a low relapse rate. However, conditioning with 30 mg/kg rather than 45 mg/kg etoposide resulted in less toxicity and a better overall survival due to a lower transplant-related mortality. Bone Marrow Transplantation (2000) 26, 711-716.
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PMID:Dose-dependent effect of etoposide in combination with busulfan plus cyclophosphamide as conditioning for stem cell transplantation in patients with acute myeloid leukemia. 1104 50

In this study we compared the lymphocyte reconstitution in 13 multiple myeloma (MM), nine acute myeloid leukemia (AML) and 10 chronic myeloid leukemia (CML) patients after allogeneic G-CSF-mobilized PBSC transplantation from HLA-identical siblings. Conditioning regimens included standard total body irradiation + cyclophosphamide (CY), or busulphan + CY, whereas VP-16 was added in patients with advanced disease. Overall comparable numbers of mononuclear cells, CD34+ cells and CD3+ T cells were infused in each group. A significantly higher CD3+ T cell number was observed in MM and AML than in CML patients 1 month after transplant. However, MM patients showed a faster and better recovery of CD4+ T cells than both AML and CML patients at 3 months (P = 0.01 and P = 0.01, respectively) and 12 months (P = 0.01 vs AML, while P = NS vs CML) after transplant, and had a CD4:CD8 ratio > 1 with a median CD4+ T cell value > 400/microl 1 year after transplant. Development of acute graft-versus-host disease (GVHD) did not affect CD4:CD8 ratios but patients who experienced acute GVHD > grade I had lower CD4+ and CD8+ T cell numbers at all time points. However, after excluding patients with GVHD > grade I, MM patients still showed a significantly higher CD4+ T cell value than patients with myeloproliferative diseases 1 year after transplant. These findings suggest that although allogeneic PBSC transplantation induces rapid immune reconstitution, different kinetics may occur among patients with hematological malignancies. In particular, the rapid reconstitution of CD4+ T cells in MM patients may contribute to the low transplant-related mortality achieved in this disease.
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PMID:Different immune reconstitution in multiple myeloma, chronic myeloid leukemia and acute myeloid leukemia patients after allogeneic transplantation of peripheral blood stem cells. 1122 73

A 3-year-old boy with poorly prognostic acute megakaryoblastic leukemia (AML M7) showing t(16;21)(p11;q22) karyotype underwent unrelated bone marrow transplantation (U-BMT) during his first hematological remission. The conditioning regimen consisted of BU, VP-16 and L-PAM. Engraftment was smooth, but the patient developed grade I acute GVHD. During hematological remission before U-BMT, the TLS/FUS-ERG chimeric transcript of t(16;21)(p11;q22) was consistently detectable as minimal residual disease (MRD) by RT-PCR. However, after U-BMT it soon became undetectable. There was no detectable MRD until 7 months after U-BMT, but bone marrow relapse occurred 10 months after U-BMT. We consider that U-BMT is a promising treatment for t(16;21)(p11;q22) AML. However, an intensified conditioning regimen or modification of GVHD prophylaxis is needed.
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PMID:[AML(M7) associated with t(16;21)(p11;q22) showing relapse after unrelated bone marrow transplantation and disappearance of TLS/FUS-ERG mRNA]. 1150 30

A 23-year-old female patient was diagnosed as having Hodgkin lymphoma (mixed cellularity type, clinical stage III B) in September 2000. She underwent ABVD chemotherapy and irradiation of a mediastinal lesion, resulting in complete remission. However, the disease reoccurred three month after the completion of initial treatment. She was admitted to our hospital for allogeneic stem cell transplantation. Thoractic vertebra, lumbar vertebra and iliac bone lesions were detected by FDG-PET, and a diagnosis of bone marrow infiltration was made. She received re-induction chemotherapy but did not achieve complete remission. A residual lesion in her bone marrow was detected by FDG-PET. She underwent unrelated allogeneic bone marrow transplantation in May 2002. Preconditioning was VP-16, CY and TBI. Engraftment of white blood cells was on day 15. Skin GVHD was detected at the same time and she was treated with steroid hormones, resulting in improvement. No residual mass could be detected by FDG-PET on day 60. However, she suffered from fever on day 80. Aggravation of the disease was revealed and she died from progression of the disease on day 120. FDG-PET is useful for the monitoring disease status and for determining the optimal timing of various treatments.
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PMID:[Evaluation of bone marrow involvement by FDG-PET for refractory Hodgkin lymphoma treated by unrelated allogeneic bone marrow transplantation]. 1293 62

A 51-year-old female with acute myeloid leukemia was admitted to our hospital in December 2001. Though she had undergone two courses of induction chemotherapy (idarubicin hydrochloride + cytarabine), she failed to achieve a complete remission. In April 2002, while in non-complete remission, she subsequently underwent total body irradiation (TBI) and treatment with cyclophosphamide (CY) and etoposide (VP-16) before receiving an allogeneic peripheral blood stem cell transplant from her HLA-identical brother. For graft-versus-host disease (GVHD) prophylaxis, she was given tacrolimus and methotrexate. The infused CD34 positive cells provided 8.1 x 10(6) cells per kg. Engraftment was obtained on post-transplant day 14, and there was no evidence of clinical acute GVHD. The use of tacrolimus was discontinued on post-transplant day 60. As there was no occurrence of clinical acute GVHD, the patient received a donor lymphocyte infusion (CD3 cells 0.57 X 10(7) cells per kg) on post-transplant day 105. On day 132, however, she complained of coughing and fever, and on day 135, she was admitted to our hospital again for dyspnea. A CT scan demonstrated ground-glass opacity in the right pulmonary lobe. After considering her clinical course, symptoms, blood gas, CT scans, etc., we suspected interstitial pneumonia. The dyspnea progressively worsened, however, and despite the use of mechanical ventilation from day 143, the patient died on day 149. From the day she was admitted till the day she was intubated, she was unable to produce sputum. Autopsy findings revealed yellow-white tracheal pseudomembranes, as well as Aspergillus hyphae in the trachea, bronchus, and bilateral lungs. These findings are characteristic of Aspergillus tracheobronchitis. The clinical course of Aspergillus tracheobronchitis in allogeneic stem cell transplant recipients is, however, different from that of the usual invasive Aspergillus infection, and although Aspergillus tracheobronchitis is a very rare disease, attention should be paid to the possibility of its occurrence.
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PMID:[Acute myeloid leukemia with Aspergillus tracheobronchitis after allogeneic peripheral blood stem cell transplant]. 1551 Aug 28

The role of T-cell depletion (TCD) to prevent graft-versus-host disease (GVHD) after matched unrelated donor allogeneic bone marrow transplant (MUD BMT) remains undefined. Most studies employ total body irradiation and pan TCD. Between March 1993 and June 2002, we treated 33 relapsed acute myelogenous leukemia (AML) patients with busulfan-based preparative regimens and selective TCD. The preparative regimen consisted of busulfan 14 mg/kg, cyclophosphamide 120 mg/kg and VP-16 50 mg/kg in all but one patient who only received busulfan and cyclophosphamide. Donor marrow was depleted of CD8+ T cells by immunomagnetic bead separation. The patients were also treated with cyclosporine and methylprednisolone or FK-506 and mini-dose methotrexate. Four (15%) of 33 patients developed graft failure or rejection. However, three of these patients were serologically mismatched at HLA-Cw. Although 67% of evaluable patients developed acute GVHD, severe grade III-IV acute GVHD only developed in 19%. The severity of acute GVHD correlated with the degree of CD8+ TCD. Median relapse-free survival was 5 months among 20 patients treated with active AML, and 28 months among 13 patients treated in complete remission. Our results confirm that MUD BMT with CD8+ TCD for AML is a potentially curative treatment option.
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PMID:CD8+ T-cell-depleted, matched unrelated donor, allogeneic bone marrow transplantation for advanced AML using busulfan-based preparative regimens. 1558 Feb 82

To analyze the relationship between the cellular composition of peripheral blood allografts and clinical outcome, we performed a prospective study in 45 adult patients who underwent allogeneic peripheral blood hematopoietic stem cell transplantation (HSCT) from a histocompatibility leukocyte antigen identical sibling donor for different hematological malignancies. The dose of CD34+, CD3+, CD4+, CD8+, and CD19+ lymphocytes, natural killer (NK) cells, natural killer T (NKT) cells, type 1 and type 2 dendritic cells (DC1 and DC2), as well as regulatory T (Treg) lymphocytes was analyzed. All patients were conditioned with busulphan and cyclophosphamide (BuCy2) +/- VP-16 and received a short course of methotrexate and cyclosporin-A as graft-versus-host disease (GVHD) prophylaxis. Acute GVHD (aGVHD) was present in 9 of 43 (21%) patients, and chronic GVHD (cGVHD) developed in 18 of 39 (46%) patients. There was a significantly higher incidence of aGVHD in patients receiving more than 6x10(6)/kg CD34+ cells. In univariate analysis, variables associated with better survival were as follows: a dose of less than 1.5x10(7)/kg NKT cells and less than 1.7x10(6)/kg DC2 for disease-free survival (DFS), and a dose of less than 3x10(7)/kg NK cells, less than 1.5x10(7)/kg NKT cells, less than 3x10(6)/kg DC1, and less than 1.7x10(6)/kg DC2 for overall survival (OS). In the Cox regression analysis, the dose of NKT cells was the only variable associated with better DFS, while the doses of NK, NKT, and CD34+ cells (less than 8x10(6)/kg) were associated with better OS. In conclusion, different circulating cell populations, other than CD34+ cells, are also of relevance in predicting the clinical outcome after allogeneic peripheral blood HSCT.
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PMID:Clinical relevance of NK, NKT, and dendritic cell dose in patients receiving G-CSF-mobilized peripheral blood allogeneic stem cell transplantation. 1631 34

Nasal natural killer (NK)/T cell lymphoma is a rare entity of non-Hodgkin's lymphoma which mostly occurs in East Asian countries. The advanced disease above clinical stage III is often refractory to the radiation and chemotherapies, remission is transient even if achieved, and median survival is about 12 months. Thus the prognosis of advanced NK/T cell lymphoma is generally poor, however, the promising results of allogeneic hematopoietic stem cell transplantation for advanced NK/T cell lymphoma have been recently reported. In most of these cases, stem cell sources were human leukocyte antigen (HLA) matched donors and alternative sources were seldom used. We report here a case of a 36-year-old woman who was diagnosed as having an extranodal NK/T cell lymphoma, nasal type. The patient achieved a complete remission after 2 cycles of chemotherapy including Carboplatin, Etoposide, Ifosfamide, and Dexamethasone, but 3-months later relapsed during the search for HLA-matched unrelated donors. She received unrelated cord blood transplantation (CBT) in the second remission achieved by a regimen containing L-asparaginase. The conditioning regimen was 12 Gy of total body irradiation, high-dose cytarabin and cyclophosphamide. FK506 and methotrexate were used for graft-versus-host disease (GVHD) prophylaxis. GVHD involving the intestine and the oral mucosa was observed, but improved without additional immunosuppressive therapies. The patient remains in remission 33 months after CBT. Cord blood thus could be an appropriate stem cell source for patients with advanced NK/T lymphoma who have no HLA matched donors.
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PMID:Successful treatment of advanced extranodal NK/T cell lymphoma with unrelated cord blood transplantation. 1740 80

We retrospectively evaluated the outcomes of 37 adult patients with acute lymphoblastic leukemia (ALL) undergoing allogeneic hematopoietic stem cell transplantation (allo-SCT) conditioned with medium-dose VP-16 (VP, 30 mg/kg), cyclophosphamide (CY, 120 mg/kg), and fractionated total-body irradiation (TBI, 12 Gy) (medium-dose VP/CY/TBI). The median age of the patients was 26 years. Thirteen patients underwent transplantation from HLA-matched related donors (MRD), 18 patients underwent transplantation from HLA-matched unrelated donors (MUD), and 6 patients underwent transplantation from HLA-mismatched donors (MMD). Thirty-two patients received bone marrow and 4 patients received peripheral blood stem cells. Ten patients were Philadelphia chromosome-positive (Ph(+)) and 35 patients were in complete remission (CR) at transplantation. All of the patients achieved engraftment, and grade 3 organ toxicity before engraftment occurred in 27 patients. Grade II-III acute graft-versus-host disease (GVHD) and chronic GVHD (cGVHD) occurred in 15 and 18 patients, respectively. No patient developed grade IV acute GVHD (aGVHD) or died of GVHD. At median follow-up of 35.1 months, 32 patients were alive and all Ph(+) patients were alive. Three patients died of relapse and 2 died of transplant-related mortality (TRM). The actuarial 3-year overall survival (OS) rate, relapse rate, and TRM rate were 89.2%, 8.1%, and 5.4%, respectively. Non-CR at transplantation, MRD, and no aGVHD were significant adverse prognostic factors for survival. Medium-dose VP/CY/TBI for adult ALL patients was associated with lower relapse rate and no increase in toxicity, resulting in better survival.
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PMID:Excellent outcome of allogeneic hematopoietic stem cell transplantation using a conditioning regimen with medium-dose VP-16, cyclophosphamide and total-body irradiation for adult patients with acute lymphoblastic leukemia. 1841 Aug 99

We report a 4-year-old girl who presented with acute onset of hemophagocytic syndrome (HPS) after induction therapy and HPS relapsed immediately after reduced-intensity cord blood transplantation (RI-CBT) for relapse of acute lymphoblastic leukemia. The patient underwent CBT from 2 locus-mismatched donor, after reduced-intensity conditioning therapy consisting of fludarabine, melphalan, and total body irradiation 4Gy. Prednisolone and cyclosporine were administered for prophylaxis against graft-versus-host disease. Bone marrow examination on day 20 revealed activated macrophages displaying hemophagocytosis. The origin of macrophages was 2(nd) donor derived. After administration of steroids, intravenous immunoglobulin and VP-16, the patient exhibited complete chimerism and remained in complete remission for over one year.
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PMID:[Early relapse of hemophagocytic syndrome after reduced-intensity cord blood transplantation for relapsed acute lymphoblastic leukemia]. 2037 15


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