Impact of Day +11 Methotrexate on the Incidence of Graft-versus-host Disease after HLA-identical Allogeneic Peripheral Blood Stem Cell Transplantation

BACKGROUND: Cyclosporine (CSA) plus 4 doses of methotrexate (MTX) is the commonly used regimen for GVHD prophylaxis. It has been previously found that the omission of the day +11 dose of MTX was associated with an increased risk of acute GVHD in the allogeneic BMT setting. However, little is known about its impact in the PBSCT setting. METHODS: Of the 68 patients, 30 patients (44%) received 4 doses of MTX (the MTX4 group), while 38 patients (56%) received less than 4 doses (the MTX3 group) because of their severe mucositis, hepatic dysfunction or renal failure. RESULTS: The cumulative incidence of acute GVHD was 60% in the MTX4 and 86% in the MTX3 group (P=0.038), while that of grade III and IV acute GVHD was 7% in the MTX4 group and 39% in the MTX3 group (P=0.017). Of the 61 patients evaluated for chronic GVHD, the cumulative incidence of chronic GVHD was 54% in the MTX4 group and 97% in the MTX3 group (P=0.001), while that of extensive chronic GVHD was 26% in the MTX4 group and 63% in the MTX3 group (P=0.004). There were no differences in the overall survival and the incidence of relapse between the two groups. On multivariate analyses, MTX3 was a poor prognostic factor in terms of acute GVHD and extensive chronic GVHD. CONCLUSION: This study suggested that omitting day +11 MTX and the clinical situation of the MTX3 group seemed to be associated with an increased incidence of acute and chronic GVHD. Accordingly, administration of day +11 MTX accompanied by active treatment of mucositis may prevent GVHD in the allogeneic PBSCT setting, but we need to conduct a large scale prospective study.

Single Center Experience of Allogeneic Peripheral Blood Stem Cell Transplantation for Acute Myeloid Leukemia / 대한혈액학회지

BACKGROUND: Recently, peripheral blood (PB) stem cells have been used widely for allogeneic stem cell transplantation (SCT), instead of bone marrow (BM). The current study analyzed the outcome of allogeneic PBSCT for the patients with acute myeloid leukemia (AML). METHODS: Twenty-nine patients with AML excluding AML M3 were included for the analysis. PB stem cells were collected from HLA-matched sibling donors mobilized with G-CSF with or without GM-CSF. RESULTS: Engraftment for neutrophil and platelet were achieved in a median 15.0 days and 14.0 days, respectively. The incidence of grade II~III acute graft versus host disease (GVHD) was 82.8% (24/29 patients), while of chronic GVHD 78.6% (22/28 patients, limited 11, extensive 11). During the median follow-up of 340 days (range, 86~1,603 days), 3 years overall survival and disease free survival was 51.4% and 40.0%, respectively. CONCLUSION: PB may be considered as a feasible source of allogeneic SCT for patients with AML.

Clinical Outcomes according to Transplanted CD34+ Cell Dose in Allogeneic Peripheral Blood Stem Cell Transplantation / 대한혈액학회지

BACKGROUND: Recently, allogeneic peripheral blood stem cell transplantation (Allo-PBSCT) instead of bone marrow transplantation (BMT) has been widely used with the benefits of an earlier recovery of blood cells and a lower incidence of graft failure because of higher CD34+ cell dose. However, recent studies suggested that the higher dose of CD34+ cells might be related to the lower survival and the higher morbidity due to chronic graft versus host disease (cGVHD). We have analyzed the impact of transplanted CD34+ cell dose on clinical outcomes in unmanipulated allo-PBSCT from HLA identical siblings. METHODS: Thirty-one consecutive adult patients with hematological diseases, who survived until at least day 90 after allo-PBSCT and were evaluable for cGVHD, were included. Peripheral blood stem cells were collected from HLA-matched sibling donors mobilized with G-CSF and/or GM-CSF. The patients were classified into a "low" or "high" CD34+ cell dose group based on whether they received less or more than a median CD34+ cell dose of 11.17X10(6)/kg, respectively. RESULTS: The median CD34+ cell dose was 11.17X10(6)/kg (range, 4.12-58.80X10(6)/kg). Acute GVHD (grade II-IV) appeared in 24 patients (77.4%) and extensive cGVHD in 14 patients (45.2%). During the follow-up (median: 340 days, range: 111-1263 days), relapses were observed in 12 patients (38.7%) and 19 patients are still alive. There was a significant difference in the incidence of extensive cGVHD (20.0% vs 68.8%, P=0.011) and relapse (60.0% vs 18.8%, P=0.029) between low and high CD34+ cell dose groups, but no difference of the incidence of acute GVHD or the days of engraftments between the two groups. The estimated survival rate was significantly different between the two groups (3 year survival rate, 31.5% vs 79.8%, P=0.022) and the patients with extensive cGVHD showed a higher survival rate than those without extensive cGVHD (55.6% vs 12.5%, P=0.013). CONCLUSION: Better survival rate was observed in high CD34+ cell dose group for alloPBSCT, while a higher incidence of extensive cGVHD was noted. The optimal dose of CD34+ cells need to be determined to minimize the morbidity related to cGVHD and to improve survival.

Allogeneic Peripheral Blood Stem Cell Transplantation from An HLA-identical Sibling Donor in Children / 대한소아혈액종양학회지

PURPOSE: G-CSF-mobilized peripheral blood is one of the sources of allogeneic hematopoietic stem cells. We report our experiences on allogeneic peripheral blood stem cell transplantation (allo-PBSCT) from an HLA-identical sibling donor in children. METHODS: From August 1998 to January 2003, 8 patients underwent allo-PBSCT. Median age of recipients and donors were 4 yr 10 mo (range 3 yr 2 mo 15 yr) and 5 yr 1 mo (range 1 yr 11 mo 19 yr 8 mo), respectively. Seven patients (3 ALL, 2 neuroblastomas, 1 AML, 1 Gaucher disease) had failed from previous allogeneic or autologous transplant and 1 patient had refractory acute biphenotypic leukemia. Only 2 patients were in complete remission at allo-PBSCT. G-CSF 10mug/kg/day was injected subcutaneously to the donor for 5 days and large volume leukapheresis was performed on 4th and 5th days. RESULTS: Median number of CD34 and CD3 cells infused was 18.55 106 (range 9.47 84.76) /kg and 8.26 108 (range 0.88 24.58) /kg, respectively. All patients achieved ANC > 0.5 109/L after a median of 9 days and 6 patients eventually achieved platelet engraftment. There was no grade II-IV acute GVHD but limited chronic GVHD developed in 6 evaluable patients. There was no CMV antigenemia. Three patients died from either transplant-related mortality (n=2) or relapse (n=1). The remaining 5 patients are alive disease-free for 7, 8, 15, 16, and 19 months from allo-PBSCT, respectively. CONCLUSION: Our results suggest that mega-dose allo-PBSCT from an HLA-identical sibling donor is expected to improve transplant outcome especially in very high risk pediatric patients.

Faster reduction of the immunosuppressive drug dosage in early stage of allogeneic peripheral blood stem cell transplantation for patients with refractory or relapsed leukemia / 中国实用内科杂志

Objective To investigate early reduction of the dose of immunosuppressive drug after allogeneic peripheral blood stem cell transplantation(allo-PBSCT)for patients with refractory or relapsed leukemia.Methods Between Janaury 2004 and December 2006,15 patients with relapsed or refractory leukemia in Department of Hematology,the First Affiliated Hospital,Sun Yat-Sen University and Institute of Hematology & Blood Diseases Hospital,CAMS & PUMC,received allo-PBSCT from their relatives,12 from HLA-identical siblings.The preparative regimens included BuCy and TBICy with or without cytarabine.Cyclosporine A(CsA)or tacrolimus was used for graft-versus-host disease(GVHD)prophylaxis,with rapid decreasing starting on day 30 of post transplant if no GVHD appeared in receipts of matched sibling tranplantation.Results(1)Faster engraftment was achieved in all patients.Grade Ⅰ~Ⅱ acute GVHD appeared in 5 patients.Chronic GVHD occured in 7 of 11 evaluable patients.(2)Of 9 patients with an lower CsA or tacrolimus dosage,only 1 developed grade Ⅰ acute GVHD,4 chronic GVHD,2 extramedullary relapse.(3)After a median follow-up of 328 days,8 patients has leukemia-free-survival(LFS),4 relapsed,and only 1 had transplantation-related mortality(TRM)in the first 3 months post-transplant.The estimated LFS at 1 year and 2 years was 51% and 25%,respectively.Conclusion Patients with advanced leukemia might benefit from allo-PBSCT with significant lower treatment failure incidence.Dose reductions of CsA and tacrolimus in early transplant might enhance graft-versus-leukemia effect,and improve long-term LFS.

NONMYELOABLATIVE ALLOGENEIC PERIPHERAL BLOOD STEM CELL TRANSPLANTATION FROM UNRELATED DONOR FOR TREATMENT OF ACUTE LYMPHOBLASTIC LEUKEMIA:THE FIRST CASE REPORT / 解放军医学杂志

The purpose of this study was to investigate the clinical efficacy against acute leukemia by transplantation of nonmyeloablative allogeneic peripheral blood stem cells from unrelated donor (URD NAPBSCT). One patient with acute lymphoblastic leukemia received URD NAPBSCT in our hospital. The donor cells were full engafted, and grade Ⅱ skin aGVHD and interstitial pneumonia were developed. The results showed that URD NAPBSCT is an effective new method for the treatment of acute leukemia.

Single Center Report on the Variety of Clinical Applications of Allogeneic Peripheral Blood Stem Cell Transplantation / 대한혈액학회지

BACKGROUND: It is apparent that more stem cells can be harvested by mobilization treatment with recombinant human G-CSF and/or GM-CSF from normal healthy donors in allogeneic peripheral blood stem cell transplantation (allo-PBSCT) compared to allogeneic bone marrow transplantation (allo-BMT). It is also known to be more effective in inducing the graft-vs-tumor effects than allogeneic BMT because of higher T cell content. METHODS: A variety of clinical applications with allo-PBSCT was done for patients with he matological malignancies with a high risk of relapse in single transplantation center. We reported the preliminary results on trial of allo-PBSCT followed by planned prophylactic G- and/or GM-CSF primed donor lymphocyte infusion additionally reserved at harvest in hematological malignancies with a high risk of relapse and also presented the successful trial of non-myeloablative transplantation for old aged AML patient in 4th complete remission and cases with 2nd transplantation with allo-PBSCs. RESULTS: Seventeen patients with hematological malignancies with a high risk of relapse were enrolled in trial of allo-PBSCT followed by prophylactic donor lymphocyte infusion. All patients received allogeneic PBSCT from HLA- matched sibling donors. Seven out of 17 patients received additional PBSCs with a median number of CD3+ cells of 5.0x107/kg (range, 3.0 to 9.9x107/kg), between day 41 and day 120. Four surviving patients (4/7) were free of disease when last assessed (median follow-up duration, 538 days), but were suffering from chronic GVHD (1 limited and 3 extensive). A 56 year old acute myeloid leukemia patient in the 4th complete remission was successfully treated with allo-PBSCT with non-myeloablative conditioning regimen. One of 2 patients who received second transplantation with allo-PBSCT has shown a long term disease free survival. CONCLUSION: A merit of allo-PBSCT would allow us to design a variety of clinical applications. Allo-PBSCT might be preferable in special clinical setting such as non-myeloablative transplantation, second transplantation, or the situation in need of the strong GVL effect. And also CSF-primed PBSCs can be used for the purpose of donor lymphocyte infusion.

A Case of DNA Chimerism Analysis as a Marker of Donor Lymphocyte Infusion / 대한혈액학회지

Donor lymphocyte infusion (DLI) has some benefit effects as graft-versus-leukemia effect, reducing the relapse of leukemia and inducing of a complete remission. But it has also a graft-versus-host-disease (GVHD) effect. So it is required a proper marker test when DLI is performing. The DNA chimerism analysis can be a marker test in DLI. Variable number of tandem repeats (VNTR) are highly polymorphic DNA markers in the human genomic DNA and used as primers of DNA chimerism analysis. A 43-year-old male who had been diagnosed acute myelogenous leukemia was transplanted with allogeneic peripheral blood stem cells. The initial chimerism analysis showed complete chimerism but it changed to mixed chimerism after 7 months of transplantation. We predicted the relapse of leukemia and performed DLI. The patient could obtain the complete chimerism after DLI. We report a case of chimerism analysis which was useful to predict the relapse of leukemia and perform the DLI.

ABO-incompatible sibling allogeneic peripheral blood stem cell transplantation (allo-PBSCT) / 中国输血杂志

0.05).Conclusion ABO-incompatible allo-PBSCT is fairly safe if there is indication. There was no influence on engraftment, incidence of GVHD or prognosis. However, an O to A group transplantation contributes significantly to the post-transplant PRCA.