scholarly journals A randomized study of cyclosporine and methotrexate with or without methylprednisolone for the prevention of graft-versus-host disease: Improved long-term survival with triple prophylaxis

Cancer ◽  
2017 ◽  
Vol 124 (4) ◽  
pp. 727-733 ◽  
Author(s):  
Tapani Ruutu ◽  
Anne Nihtinen ◽  
Riitta Niittyvuopio ◽  
Eeva Juvonen ◽  
Liisa Volin
Blood ◽  
2010 ◽  
Vol 116 (21) ◽  
pp. 2336-2336
Author(s):  
Lynne Margaret Ball ◽  
Maria E. Bernardo ◽  
Jaap Jan Zwaginga ◽  
Maarten van Tol ◽  
Angela Cometa ◽  
...  

Abstract Abstract 2336 Mesenchymal stromal cell (MSC) infusions have been reported to be effective in patients with severe, steroid-refractory, acute graft-versus-host disease (aGVHD). However, long term comprehensive follow up data on pediatric patients is limited. We analyzed the outcome of 37 children receiving MSC for steroid-refractory aGvHD in two centers between January 2005 and December 2009 (characteristics see Table 1). A median of 2 infusions (range 1–13) were administered, with a median cell dose of 2×106/kg (range 0.9–3.0). MSC were from 3rd party HLA-mismatched donors (n=31), haploidentical relative (n=3) or both (n=3). (see Table 2) Fifteen children had either no (n=6) or partial (n=9) response to MSC. In this group, transplantation-related mortality (TRM) was 60%. Complete response (CR) was observed in 22 children, TRM being 14%. (p=0.005). Among the 28 patients with hematological malignancies, 5 relapsed, three with CR and two with PR. With a median follow-up of 2.3 years (range 7 months–4.7 years), overall survival was 62% with 87% versus 27% in patients who did or did not achieve CR after MSC respectively (p value <0.001). MSC after 2009 given at the time of steroid failure (median 8 days range 4 to 24) compared to pre 2009 (median 24 days range 5 to 85) (Maan-Whitney U = 65.5 two tailed p= 0.002) reduced fatal infections and was associated with a trend to better overall survival at 2 years post MSC infusion (p = 0.07). Although infections were evident at the time of immune suppression and mortality was high in NR/PR, response to MSC allows for reduction and eventual discontinuation of pharmacological immune suppression. Long term survival in responders is associated with eventual immune recovery, no late infections and persistent remission status. Treatment of steroid refractory aGVHD should aim to induce rapid stable control and early reduction of steroids to reduce TRM from viral reactivations. We conclude that MSC are ideal candidates for this purpose. Our results show that children responding to MSC treatment for severe steroid refractory GvHD have an excellent long term survival. Legend: ALL = acute lymphoblastic leukemia; AML = acute myeloid leukemia; MDS = myelodysplastic syndrome; jMML = juvenile myelomonocytic leukemia; HLH = hemophagocytic lymphohistiocytosis; MSD = matched sibling donor; (m) MUD (mis) Matched unrelated donor; PBSC = peripheral blood stem cells; TBI = total body irradiation; CSA = Cyclosporine A; MTX = short course methrotrexate; ATG = anti-thymocyte globulin; HSCT = hematopoietic stem cell transplantation; DLI = donor lymphocyte infusion; GvHD = graft versus host disease; M=Male; F=Female. Disclosures: No relevant conflicts of interest to declare.


Blood ◽  
2004 ◽  
Vol 104 (11) ◽  
pp. 5107-5107
Author(s):  
Binyi Wu ◽  
Lanxiao Wu ◽  
Kunyuan Guo ◽  
Chaoyang Song ◽  
Dingan Yan ◽  
...  

Abstract Objective: To evaluate the factors effecting the long term survival of refractory leukemia patients who received the therapy of HLA haploidentical peripheral blood stem cells transplantation. Methods: To analysis the factors effecting long term survival of refractory leukemia patients who underwent HLA haploidentical peripheral blood stem cells transplantation. The HLA mismatched locus between the donors and patients, the disease status of patients at transplant, the grafted mononucleaer cells number, and the occurrence of GVHD, the age of patients and other factors were considered and analyzed by data reduction SSP11. From July, 1998 to May, 2004, 30 Patients with refractory leukemia patients including 13 cases of acute non-lymphocytes leukemia, 10 cases of acute lymphocytes leukemia, 6 cases chronic myeloid leukemia and 1 cases of non-Hodgkin lymphoma underwent HLA haploidentical peripheral blood stem cells transplantations. The median age was 25 years old (3– 52 years old). Twelve patients received stem cells from parents, four from daughter and son, and the other from sibling donors. Twelve patients received three HLA locus mismatched stem cells, thirteen patients received two HLA mismatched donors stem cells, and five patients received one HLA mismatched donors stem cells. The conditioning regime consisted of fludara (25mg/m2 X5d), busufan (4mg/kg X4d) and cyclophosphamide ( 60mg/kg X2d). Median dose of rabbit anti-human lymphocyte globulin (5mg/kg X5d) was added in the in some patients. A mean of 6.0 x 108 /kg (3–9 x108 /kg) mono-nucleated cells was grafted. The mean CD34+ cells number was 5.5 x106 /Kg (3–6.5 x106/kg). Results: Twenty-nine patients were successfully grafted and one failed to graft. The mean time of white cell count more than 1x109/L was 13 days (10–18 days) and 12 days (9–16) respectively. Severe acute graft versus host disease occurred in six patients, and four died. Seven patients suffered from intensive chronic graft versus host disease. Nine patients relapsed and died. The mean relapse time was 10 months (3 months to 24 months). Four patients died from intensive chronic graft versus host disease. Fourteen patients are still disease free survival with high karnofsky performs. The relapse of leukemia was the main cause of death. Five the patients less than 20 year’s old age are still disease free survival with high karnofsky performs scores. Conclusion: HLA haploidentical peripheral blood stem cells transplantation may be an effect therapy for refractory leukemia. Although graft versus leukemia effect may be strong in HLA haploidentical blood stem cells transplantation, leukemia relapse is still the main cause to death. We suggest that for these patients with leukemia who can not find full matched donor perform related HLA mismatched peripheral blood stem cells transplantation as earlier as to get the better long term outcome.


2018 ◽  
Vol 13 (6) ◽  
pp. 866-873 ◽  
Author(s):  
Sangeeta Hingorani ◽  
Emily Pao ◽  
Phil Stevenson ◽  
Gary Schoch ◽  
Benjamin L. Laskin ◽  
...  

Background and objectivesKidney injury is a significant complication for patients undergoing hematopoietic cell transplantation (HCT), but few studies have prospectively examined changes in GFR in long-term survivors of HCT. We described the association between changes in GFR and all-cause mortality in patients up to 10 years after HCT.Design, setting, participants, & measurementsWe conducted a prospective, observational cohort study of adult patients undergoing HCT at the Fred Hutchinson Cancer Center in Seattle, Washington from 2003 to 2015. Patients were followed from baseline, before conditioning therapy, until a maximum of 10 years after transplant. We used Cox proportional hazard models to examine the association between creatinine eGFR and all-cause mortality. We used time-dependent generalized estimating equations to examine risk factors for decreases in eGFR.ResultsA total of 434 patients (median age, 52 years; range, 18–76 years; 64% were men; 87% were white) were followed for a median 5.3 years after HCT. The largest decreases in eGFR occurred within the first year post-transplant, with the eGFR decreasing from a median of 98 ml/min per 1.73 m2 at baseline to 78 ml/min per 1.73 m2 by 1 year post-HCT. Two thirds of patients had an eGFR<90 ml/min per 1.73 m2 at 1 year after transplant. When modeled as a continuous variable, as eGFR declined from approximately 60 ml/min per 1.73 m2, the hazard of mortality progressively increased relative to a normal eGFR of 90 ml/min per 1.73 m2 (P<0.001). For example, when compared with an eGFR of 90 ml/min per 1.73 m2, the hazard ratios for eGFR of 60, 50, and 40 ml/min per 1.73 m2 are 1.15 (95% confidence interval, 0.87 to 1.53), 1.68 (95% confidence interval, 1.26 to 2.24), and 2.67 (95% confidence interval, 1.99 to 3.60), respectively. Diabetes, hypertension, acute graft versus host disease, and cytomegalovirus infection were independently associated with a decline in GFR, whereas calcineurin inhibitor levels, chronic graft versus host disease, and albuminuria were not.ConclusionsAdult HCT recipients have a high risk of decreased eGFR by 1 year after HCT. Although eGFR remains fairly stable thereafter, a decreased eGFR is significantly associated with higher risk of mortality, with a progressively increased risk as eGFR declines.


Blood ◽  
2007 ◽  
Vol 110 (11) ◽  
pp. 5075-5075
Author(s):  
Tatsuo Ichinohe ◽  
Chihiro Shimazaki ◽  
Motohiro Hamaguchi ◽  
Arata Watanabe ◽  
Hiroyuki Ishida ◽  
...  

Abstract Background: We previously reported that T-cell-replete HLA-haploidentical hematopoietic stem cell transplantation (SCT) from a microchimeric noninherited maternal HLA antigen (NIMA)-mismatched related donor offers a feasible treatment option in patients with poor-risk hematologic malignancies who lack an immediately available stem cell source (Ichinohe T, et al. Blood2004;104:3821). However, long-term outcomes and late effects among patients undergoing such transplantation are largely unknown. Methods: We studied 16 patients who had survived more than 3 years after T-cell-replete HLA-haploidentical NIMA-mismatched SCT to evaluate the impact of late complications on morbidity and mortality. The patients received bone marrow (n=5) or peripheral blood stem cell (n=11) between 01/2001 and 07/2004 at 11 centers with a median age of 19 years (range, 2 to 56) as treatment for acute myeloid leukemia (n=6), acute lymphoblastic leukemia (n=3), chronic myeloid leukemia (n=4), and other B-cell neoplasms (n=3). At the time of SCT, 6 patients had a chemosensitive disease and 10 had a chemorefractory disease. Type of donor was NIMA-mismatched sibling in 9, mother in 6, and daughter in 1; all patient-donor pairs had two or three serologic mismatches at HLA-A, −B, and −DR in the graft-versus-host direction. Organ-specific symptoms related to chronic graft-versus-host disease (cGVHD) and their severity were evaluated by clinical scoring system proposed by the National Institutes of Health consensus development project. Results: At a median follow-up of 56 months (range, 38 to 74), 13 (81%) of 16 patients were alive and free of their primary disease. One patient was alive with relapsed disease; 2 died from bronchiolitis obliterans at 51 and 52 months in continuous remission. Karnofsky or Lansky performance score among 14 survivors was 100% in 6 (43%), 80–90% in 5 (36%), 70% in 2 (14%), and less than 70% in 1 (7%). Thirteen (81%) patients developed extensive cGVHD and eleven of them experienced organ symptoms corresponding to the consensus score greater than 1. The commonly involved organs (score>1) were lungs (n=5), skin (n=4), eyes (n=3), and liver (n=3). Seven patients were successfully withdrawn from immunosuppressive agents between 3 and 46 months (median, 19) after transplantation. Conclusions: T-cell-replete HLA-haploidentical SCT from a microchimeric NIMA-mismatched donor confers long-term survival in selected patients without compromising their performance status, although a high incidence of moderate to severe cGVHD may limit its usefulness as compared with conventional SCT.


Blood ◽  
2008 ◽  
Vol 112 (11) ◽  
pp. 4411-4411
Author(s):  
Bingyi Wu ◽  
Guo Kunyuan ◽  
Jing Wu

Abstract Objective: To assess the long term survival of patients with refractory leukemia treated by HLA haploidentical stem cell transplantation. Methods To analysis the outcomes of 48 cases patients with refractory leukemia underwent HLA haploidentical stem cell transplantations from August, 1998 to May, 2008. The median age was 16 years old (7–52 years old). Patients received stem cells from their parants, daughter, son, and sibling donors. Twelve patients received three HLA locus mismatched stem cells and twenty patients received two HLA locus mismatched donors stem cells. Sixteen patients were grafted one HLA mismatched donors stem cells. The conditioning regime consisted of fludara (25mg/m2 × 5d), busulfan (4mg/kg × 4d) and cyclophosphamide (60mg/kg × 2d). Median dose of rabbit anti-human lymphocyte globulin (5mg/kg × 5d) was added. CSA combined with short course of MTX were used for prophylaxis GVHD. A median dose of 6.0 × 108/kg(3–9 ×108/kg) mono-nucleated cells was grafted. The mean CD34+ cells number was 5.5 × 106/kg (3–6.5 × 106/kg) Results Forty-seven patients were successfully to be engraftment and one failed to be engraftment. The median time of white cells and platelet reconstitution was 14 days (11–20 days) and 18 days (14–20) respectively. Severe acute graft versus host disease occurred in seven patients, and six died. Seven patients suffered from intensive chronic graft versus host disease and four died with fungus infection. Seven patients relapsed and died. The median relapse time was 6 months (3 months to 24 months). Three patients died from severe diarrhea with CMV infection. Four patients died from intensive chronic graft versus host disease. Twenty patients are still survival and disease free with high karnofsky performance scores. The disease free survival is 45 percent as follow up 3 years (1 to 7 years). Conclusion: HLA haploidentical peripheral blood stem cell transplantation may be an effect therapy to refractory leukemia. And some refractory leukemia patients could benefit from HLA haploidentical peripheral blood stem cell transplantation.


2021 ◽  
pp. 021849232110443
Author(s):  
Masaki Ikeda ◽  
Hideki Motoyama ◽  
Makoto Sonobe ◽  
Hiroshi Date

We report two cases of long-term survival after single living-donor lobar lung transplantation with contralateral pneumonectomy. An 8-year-old female with pulmonary graft-versus-host disease after cord-blood transplantation underwent single living-donor lobar lung transplantation with simultaneous contralateral pneumonectomy due to an oversized graft. She has been performing daily life activities for ≥11 years with limited physical development. A 41-year-old female with short stature underwent single living-donor lobar lung transplantation due to pulmonary graft-versus-host disease after peripheral blood stem cell transplantation. Contralateral pneumonectomy was required 7 years following living-donor lobar lung transplantation due to pneumonia in the native lung. Eleven years after living-donor lobar lung transplantation, she is able to perform daily life activities.


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