Complete Resolution of Extensive Chronic Graft-Versus-Host Disease with Ibrutinib

Blood ◽  
2015 ◽  
Vol 126 (23) ◽  
pp. 5474-5474
Author(s):  
Audrey Scholoff ◽  
Gloria Obi ◽  
Kelty R. Baker ◽  
George Carrum ◽  
Rammurti T Kamble
Keyword(s):  
Graft Versus Host Disease ◽  
Complete Resolution ◽  
Conflicts Of Interest ◽  
Complete Response ◽  
Unrelated Donor ◽  
Hematopoietic Stem ◽  
Host Disease ◽  
Graft Versus Host ◽  
Oral Ulcers

Abstract We herein document a complete response of extensive chronic graft-versus-host disease (cGvHD) to a Bruton's tyrosine kinase (BTK) inhibitor, ibrutinib. A 41 years old female with primary refractory MCL underwent mismatched unrelated donor (MMUD) allogeneic hematopoietic stem cell transplantation in December 2011 (conditioning with CY/TBI and alemtuzumab, graft=6.6x 106/kg CD-34+ cells, tacrolimus alone for GVHD prevention). Following engraftment on day 11, she developed grade III acute GvHD involving the skin and gut on day 17 of transplantation that persisted beyond 100 days post-transplant. Her cGvHD was treated with steroids, but remained active and extensive. Despite persistent cGvHD and 100% donor chimerism she relapsed in July 2012. Treatment with radiation and bendamustine with rituximab failed. By December 2013, the patient had extensive cGvHD manifesting as scleromatous skin thickening, oral ulcers and sclerosis of the buccal mucosa, ocular dryness and diarrhea, and was started on ibrutinib1 560 mg once daily for relapsed MCL. After 8 weeks of therapy, cGvHD had begun to improve. Oral steroids were reduced and ultimately stopped after 26 weeks of ibrutinib; after 30 weeks treatment all cGvHD manifestations resolved completely. A complete remission for MCL was documented at 8 weeks of ibrutinib initiation. Currently she continues to be on 560 mg daily ibrutinib without cGvHD exacerbation or MCL relapse for 22 weeks and 52 weeks, respectively. Chronic graft versus host disease (cGvHD) is mediated donor T cells. The role of B cells in the pathogenesis of cGvHD is increasingly recognized. Two murine studies have explored the role of ibrutinib in cGVHD-like syndromes, one in which there is T cell driven sclerodermatous cGvHD and a second in which there is Ab driven multiorgan system cGvHD that includes bronchiolitis obliterans (BO). Administration of ibrutinib decreased the incidence and severity of sclerodermatous, and improved pre-existing lesions and also improved pulmonary fibrosis and reduced BO. Animals lacking BTK and ITK did not develop cGVHD, indicating that these molecules are critical to cGVHD development. Our report provides the evidence that BTK inhibition led to complete resolution of cGvHD and supports exploration of its role in future clinical trials. Disclosures No relevant conflicts of interest to declare.

scholarly journals Matched and Mismatched Unrelated Donor Versus Unmanipulated Haploidentical Donors for Hematopoietic Cell Transplantation in Acute Leukemia in Remission: A Pair Matched Analysis on Behalf of the Acute Leukemia Working Party (ALWP) of the European Society for Blood and Marrow Transplantation (EBMT)

Blood ◽  
2014 ◽  
Vol 124 (21) ◽  
pp. 1219-1219
Author(s):  
Simona Piemontese ◽  
Fabio Ciceri ◽  
Myriam Labopin ◽  
William Arcese ◽  
Slawomira Kyrcz-Krzemien ◽  
...  
Keyword(s):  
Acute Leukemia ◽  
Cell Transplantation ◽  
Graft Versus Host Disease ◽  
Conflicts Of Interest ◽  
Lymphoblastic Leukemia ◽  
Adult Patients ◽  
Unrelated Donor ◽  
Hematopoietic Stem ◽  
Host Disease ◽  
Graft Versus Host

Abstract Background. The best donor source for adult patients with acute leukemia lacking an HLA-identical donor still remains to be established. The objective of this study was to compare the outcome after T-cell-replete hematopoietic stem cell transplantation from haploidentical donor (HAPLO) and transplant from Matched Unrelated Donor (MUD) or Mismatched Unrelated Donor at a single HLA-locus (MMUD) for patients with acute leukemia in remission. Methods. From January 2007 to December 2012, 313 consecutive HAPLOs were performed as first allogeneic transplants in adult patients with de novo acute leukemia in CR1 or CR2 and reported to the EBMT Registry. We were able to pair match 273 of these 313 patients with another 273 patients who received a MUD and 273 who received a MMUD transplant. The matching factors were as follow: age (+/-5y), diagnosis (myeloid or lymphoblastic leukemia), disease status at transplant (CR1 or CR2) and interval from diagnosis to transplant (+/-1mo). Results. The median follow-up was 22 months. The two-year non-relapse mortality (NRM) and relapse (RI) cumulative incidences were 28% and 30% for HAPLO, 21% and 19% for MUD, and 28% and 27% for MMUD. The two-year KM estimates of leukemia-free survival (LFS) and overall survival (OS) were 42% and 49% for HAPLO, 59% and 65% for MUD, 45% and 51% for MMUD. In multivariate analysis both NRM and RI were significantly reduced in MUD compared to HAPLO (NRM, hazard ratio (HR): 0.61, p=0.02, 95%CI: 0.40-0.91; RI, HR: 0.59, p=0.01, 95%CI: 0.39-0.89) but there was no statistical difference between HAPLO and MMUD (NRM, p=0.59; RI, p=0.52). LFS and OS were significantly higher in MUD compared to HAPLO (LFS HR: 0.61, p=0.001, 95%CI: 0.45-0.81.OS HR: 0.63, p=0.004, 95%CI: 0.46-0.86) but not statistically different between MMUD and HAPLO (LFS, p=0.45. OS, p=0.84). Of note, type of donor was neither associated with day-100 grade II-IV acute graft-versus-host disease, nor to chronic graft-versus-host disease. Conclusion. These findings suggest that LFS and OS were significantly higher in patients with acute leukemia in remission receiving a MUD compared to patients with similar characteristics receiving a HAPLO. We didn’t find significant differences between MMUD and HAPLO. In the absence of a MUD, host/donor features and urgency of transplant should drive us towards the best choice between these alternative donor sources. Disclosures No relevant conflicts of interest to declare.

Impact of clostridiodes difficile infection on acute graft-versus-host disease in allogenic transplant patients.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. e19027-e19027
Author(s):  
Prasanth Lingamaneni ◽  
Vatsala Katiyar ◽  
Rohit Kumar ◽  
Maha A.T. Elsebaie ◽  
Hashim Mann ◽  
...  
Keyword(s):  
Graft Versus Host Disease ◽  
Lymphoblastic Leukemia ◽  
Index Admission ◽  
Unrelated Donor ◽  
Cell Transplant ◽  
Hematopoietic Stem ◽  
Host Disease ◽  
Graft Versus Host ◽  
Hospitalization Costs ◽  
Acute Graft

e19027 Background: Clostridiodes difficile infection (CDI) is reported to occur up to 9-fold higher in allogenic hematopoietic stem cell transplant (HSCT) recipients compared to the general population of hospitalized patients. This is attributed to disruption of gut microbiome by antibiotics, myeloablative regimens, neutropenia, prolonged hospitalization, and immunosuppressive regimens administered to prevent acute graft-versus-host disease (aGVHD). CDI by disruption of the intestinal microbiome may trigger gastrointestinal aGVHD. Previous studies from HSCT centers have reported conflicting data on the relationship between CDI and subsequent development of aGVHD. Methods: The Nationwide Readmissions Database was queried for admissions of adult allogenic HSCT patients between 2016 and 2018. Those with and without CDI during index admission were compared. Multivariable logistic regression was used to evaluate the primary outcome of risk of aGVHD in the index admission or within 100 days post-engraftment. Results: A total of 13518 allogenic HSCT patients were included in the study. Mean age was 52.4 years. 57.2% of patients were female. The most common underlying diagnoses were acute myeloid leukemia (38%), myelodysplastic syndrome (17%) and acute lymphoblastic leukemia (14%). 11.1% of the index admissions were complicated by CDI. Rates of aGVHD during the index admission or 100 days post-engraftment were similar between CDI and non-CDI groups: 13.8% vs. 12.1%, p=0.19 during index admission and 29.2% vs. 26.1%, p=0.09 during 100 days post-engraftment. Nonetheless, patients with CDI had longer length of hospital stay (34.6 vs 29.8 days, p<0.0001), higher hospitalization costs ($608K vs $506K USD) and greater rate of inpatient mortality (7.3% vs 4.6%, p<0.001). In the multivariate regression analysis, CDI during index admission was not associated with risk of development of aGVHD (Adjusted Odds Ratio 1.14, 95% Confidence Interval 0.87-1.48, p=0.34). Age and unrelated donor HSCT were predictive of risk of aGVHD. Conclusions: CDI during index admission was not predictive of aGVHD during the first 100 days post-allogenic HSCT. HSCT patients are frequency colonized with C.difficile. Diarrhea secondary to CDI may resemble gastrointestinal aGVHD. Therefore, overdiagnosis of CDI in this population is a concern. Antimicrobial stewardship and use of clinical decision support tools have been advocated recently to decrease testing of HSCT patients with C.difficile colonization. Multivariable analysis of risk factors of aGVHD.[Table: see text]

scholarly journals The Role of Intestinal Microbiota in Acute Graft-versus-Host Disease

2015 ◽  
Vol 2015 ◽  
pp. 1-9 ◽  
Author(s):  
Yuanyuan Chen ◽  
Ye Zhao ◽  
Qiao Cheng ◽  
Depei Wu ◽  
Haiyan Liu
Keyword(s):  
Immune Responses ◽  
Intestinal Microbiota ◽  
Graft Versus Host Disease ◽  
Inflammatory Diseases ◽  
Hematopoietic Stem ◽  
Host Disease ◽  
Graft Versus Host ◽  
Host Immune Responses ◽  
Acute Graft

The mammalian intestinal microbiota is a complex ecosystem that plays an important role in host immune responses. Recent studies have demonstrated that alterations in intestinal microbiota composition are linked to multiple inflammatory diseases in humans, including acute graft-versus-host disease (aGVHD). aGVHD is one of the major obstacles in allogeneic hematopoietic stem cell transplantation (allo-HSCT), characterized by tissue damage in the gastrointestinal (GI) tract, liver, lung, and skin. Here, we review the current understanding of the role of intestinal microbiota in the control of immune responses during aGVHD. Additionally, the possibility of using probiotic strains for potential treatment or prevention of aGVHD will be discussed.

scholarly journals Methotrexate for the Treatment of Graft-versus-Host Disease after Allogeneic Hematopoietic Stem Cell Transplantation

2014 ◽  
Vol 2014 ◽  
pp. 1-10 ◽  
Author(s):  
Amr Nassar ◽  
Ghada Elgohary ◽  
Tusneem Elhassan ◽  
Zubeir Nurgat ◽  
Said Y. Mohamed ◽  
...  
Keyword(s):  
Graft Versus Host Disease ◽  
Chronic Gvhd ◽  
Corticosteroid Treatment ◽  
Complete Response ◽  
Primary Treatment ◽  
Lower Grade ◽  
Hematopoietic Stem ◽  
Host Disease ◽  
Graft Versus Host ◽  
Pooled Data

Glucocorticoids have been the primary treatment of graft-versus-host disease (GVHD) over the past decade. Complete responses to steroid therapy are usually expected in almost one-third of aGVHD cases and partial response is anticipated in another one-third of patients. However, for those patients not responding to corticosteroid treatment, there is no standard second-line therapy for acute or chronic GVHD. Methotrexate (MTX) for treatment of steroid refractory GVHD has been evaluated in a number of studies. Results from peer-reviewed original articles were identified and the pooled data analyzed. Despite several limitations in data collection and analysis, weekly administration of methotrexate at a median dose of 7.5 mg/m2seems to be safe with minimal toxicities in the context of both aGVHD and cGVHD treatments. The observed overall response (OR) in patients with aGVHD to MTX treatment in the published studies was 69.9%, with complete response (CR) in 59.2% and PR in 10.6%. In cGVHD the OR was 77.6%, with CR reported in 49.6% and PR in 28% of patients. Predictors of better responses were lower grade GVHD, cutaneous involvement, and isolated organ involvement. MTX as a steroid sparing agent might reduce long-term complications and improve the quality of life of GVHD affected individuals.

Treatment of Steroid-Resistant Graft-Versus-Host Disease with Monoclonal Antibodies in Children.

Blood ◽  
2006 ◽  
Vol 108 (11) ◽  
pp. 5310-5310
Author(s):  
Tal Schechter ◽  
Samina Afzal ◽  
Yaron Finkelstein ◽  
Gideon Koren ◽  
John Doyle ◽  
...  
Keyword(s):  
Monoclonal Antibody ◽  
Monoclonal Antibodies ◽  
Partial Response ◽  
Graft Versus Host Disease ◽  
Complete Response ◽  
Antibody Treatment ◽  
Hematopoietic Stem ◽  
Steroid Resistant ◽  
Host Disease ◽  
Graft Versus Host

Abstract Acute graft-versus-host disease (aGVHD) carries a major risk of morbidity and mortality in patients undergoing hematopoietic stem cell transplantation (HSCT). The prognosis is poor if aGVHD does not respond to corticosteroid treatment. Recently, monoclonal antibodies such as daclizumab, a humanized monoclonal IgG1, and infliximab, a chimeric monoclonal antibody that binds the precursor of tumor-necrosis factor-alfa, have shown promising results in the treatment of corticosteroid-resistant aGVHD. The reported response rate to monoclonal antibody therapy in adults with aGVHD reaches as high as 67%. Data describing the efficacy of monoclonal antibodies in children with corticosteroid-resistant aGVHD are limited. We conducted a retrospective analysis to evaluate the efficacy of daclizumab and/or infliximab in children diagnosed with steroid-resistant aGVHD in the Hospital for Sick Children, Toronto, from July 2002 to December 2005. Corticosteroid-resistant aGVHD was defined as aGVHD which did not respond or worsened after a minimum of 5 days of corticosteroid therapy. Complete response was defined as full recovery without any signs of aGVHD; partial response was defined as improvement of aGVHD symptoms in at least one organ without worsening in other organs. Sixteen children were treated for aGVHD, thirteen of them had aGVHD grade 3 or 4. The organs involved were gut (n=6), skin (n=4), liver (n=2) and multi-organ involvement (n=4). Thirteen children were given daclizumab; one was treated with infliximab and 2 children with their combination. Fourteen children received a full course of monoclonal antibodies for aGVHD. An additional child died after the first dose (from multi-organ failure) and one child developed reactive arthritis attributed to daclizumab. Seven of the 14 children (50%) who completed treatment responded: 5 had complete response and 2 had a partial response. Nine out of the 16 children died during the study period: 8 due to Transplant Related Mortality (TRM) and 1 due to relapse; three children developed fatal fungal infection and one had fatal adenovirus infection during or shortly after monoclonal antibody treatment. Median length of follow up in the remaining 7 patients was 18 months. We conclude that monoclonal antibodies were effective in the treatment of children with corticosteroid-resistant acute GVHD. The risk for infection, mainly fungal, was high.

Response to JAK 1/2 Inhibition in Patients with Corticosteroid-Refractory Acute Graft-Versus-Host Disease

Blood ◽  
2014 ◽  
Vol 124 (21) ◽  
pp. 3934-3934 ◽  
Author(s):  
Silvia Spoerl ◽  
Kristina Maas-Bauer ◽  
Mareike Verbeek ◽  
Petya Apostolova ◽  
Anna Lena Illert ◽  
...  
Keyword(s):  
Graft Versus Host Disease ◽  
Chronic Gvhd ◽  
Complete Response ◽  
Serum Levels ◽  
Salvage Treatment ◽  
Hematopoietic Stem ◽  
Host Disease ◽  
Graft Versus Host ◽  
Number Of Patients

Abstract Acute corticosteroid-refractory graft-versus-host-disease (GvHD) is a life-threatening complication of allogeneic hematopoietic stem cell transplantation (allo-HSCT) with reported mortality rates of 40-60%. Our previous study (Spoerl S et al. Blood 2014) had shown the induction of tolerogenic regulatory T cells after ruxolitinib treatment in the mouse and clinical responses in six patients with corticosteroid-refractory GvHD. Here we report the outcome of 14 patients with GvHD refractory to steroids and at least two other lines of treatment who received ruxolitinib as a salvage treatment. Ten patients were classified as acute and four as chronic GvHD involving the skin, intestinal tract and liver as detailed in Table 1. Patients were treated with ruxolitinib at a starting dose of 5 mg orally twice daily with a dose increase to 10 mg orally twice daily. Clinical and histopathological grading of skin, intestinal and liver GvHD was performed according to established criteria. Of 14 patients, 13 responded with respect to clinical GvHD symptoms and serum levels of pro-inflammatory cytokines. Three patients with histologically proven acute skin or intestinal GvHD grade I, achieved a complete response. One non-responder discontinued ruxolitinib after one week because of lack of efficacy. In all other patients corticosteroids could be reduced after a median treatment of 1.5 weeks. Serum levels of IL-6 and soluble IL-2R were measured prior and after the start of ruxolitinib and declined in the majority of the analyzed patients (n=11). CMV reactivation was observed in four out of 14 patients and responded well to antiviral therapy. Two out of 14 patients developed cytopenia during ruxolitinib treatment that was mild and did not require dose reduction or transfusion. Our results indicate that treatment of corticosteroid-refractory GvHD with ruxolitinib is safe and well tolerated. Despite the low number of patients treated so far, our results demonstrate that ruxolitinib reduces the severity of corticosteroid-refractory GvHD and support further development of therapeutic JAK1/2 inhibition as a salvage treatment in GvHD. Table 1: GvHD and response to ruxolitinib Pt. no. 1 GvHD: organ/grade 2 Reduction of cortico-steroids after ruxolitinib Clinical response (PR / CR) 3 Time to response (weeks) Duration of response 4 / Current follow up (weeks) 5 01 Intestines / IV (acute) Yes CR 1 42 / 43 02 Skin / III (acute) Yes PR 1.5 46.5 / 48 03 Skin / IV liver / III (acute) Yes CR 1 57 / 58 04 Skin / III intestines / IV (acute) Yes PR 1.5 24.5 / 26 05 Skin / III (chronic) Yes PR 1 64 / 65 06 intestine/III-IV (acute) Yes PR 1 15 / 16 07 Skin/ III (chronic) Yes Response 1 46 / 47 08 Skin/ III (acute) Yes Response 1 2 / 3 09 Skin/ II intestine/II (chronic) Yes No response stopped after 1 week N/A N/A 10 Skin/ III liver/III (acute) Yes PR 1 1 / 2 11 intestines IV (acute) Yes PR 2 6 / 8 12 Skin/III (chronic) Yes Response 1 8 / 9 13 intestines/IV Skin/ II (late onset acute) Yes CR 1 17 / 18 14 intestines/IV Skin/ II (acute) Yes PR 1,5 3 / 4 1Pt.: patient, no: individual patient number, 2Acute and chronic GvHD were defined according to NIH criteria, 3PR: partial response, CR: complete response; 4Until last follow up, none of the patients experienced a relapse of GvHD. 5Follow up was calculated from the time of initiation of ruxolitinib treatment. In patient 01, ruxolitinib was discontinued at week 16 because of complete resolution of all GvHD signs. The patient did not develop any signs of GvHD after discontinuation of ruxolitinib until last follow up. Disclosures Off Label Use: Ruxolitinib in GvHD.

scholarly journals Role of CD8 Regulatory T Cells versus Tc1 and Tc17 Cells in the Development of Human Graft-versus-Host Disease

2017 ◽  
Vol 2017 ◽  
pp. 1-11 ◽  
Author(s):  
Adriana Gutiérrez-Hoya ◽  
Rubén López-Santiago ◽  
Jorge Vela-Ojeda ◽  
Laura Montiel-Cervantes ◽  
Octavio Rodríguez-Cortés ◽  
...  
Keyword(s):  
T Cells ◽  
Regulatory T Cells ◽  
Graft Versus Host Disease ◽  
Treg Cells ◽  
Protective Role ◽  
Hematopoietic Stem ◽  
Host Disease ◽  
Graft Versus Host ◽  
Tc17 Cells

CD8+ T cells that secrete proinflammatory cytokines play a central role in exacerbation of inflammation; however, a new subpopulation of CD8 regulatory T cells has recently been characterized. This study analyzes the prominent role of these different subpopulations in the development of graft-versus-host disease (GVHD). Samples from 8 healthy donors mobilized with Filgrastim® (G-CSF) and 18 patients who underwent allogeneic hematopoietic stem cell transplantation (HSCT) were evaluated by flow cytometry. Mobilization induced an increase in Tc1 (p<0.01), Th1 (p<0.001), Tc17 (p<0.05), and CD8+IL-10+ cells (p<0.05), showing that G-CSF induces both pro- and anti-inflammatory profiles. Donor-patient correlation revealed a trend (p=0.06) toward the development of GVHD in patients who receive a high percentage of Tc1 cells. Patients with acute GVHD (aGVHD), either active or controlled, and patients without GVHD were evaluated; patients with active aGVHD had a higher percentage of Tc1 (p<0.01) and Tc17 (p<0.05) cells, as opposed to patients without GVHD in whom a higher percentage of CD8 Treg cells (p<0.01) was found. These findings indicate that the increase in Tc1 and Tc17 cells is associated with GVHD development, while regulatory CD8 T cells might have a protective role in this disease. These tests can be used to monitor and control GVHD.

scholarly journals Analysis of donor-associated factors in unrelated transplantations of hematopoietic stem cells in children with non-malignant diseases

2019 ◽  
Vol 5 (4) ◽  
pp. 31-39
Author(s):  
N. V. Sidorova ◽  
K. I. Kirgizov ◽  
A. S. Slinin ◽  
E. A. Pristanskova ◽  
V. V. Konstantinova ◽  
...  
Keyword(s):  
Graft Versus Host Disease ◽  
Conflict Of Interest ◽  
Transplant Rejection ◽  
Clinical Manifestations ◽  
Unrelated Donor ◽  
Malignant Diseases ◽  
Hematopoietic Stem ◽  
Host Disease ◽  
Graft Versus Host ◽  
Negative Effect

The choice of the optimal donor in the absence of an HLA-compatible relative, as well as the analysis of the risks of hematopoietic stem cell transplantation (HSCT), is extremely important, especially in patients with non-cancerous diseases. The article analyzes 99 allogeneic HSCTs from unrelated donors in the bone marrow transplantation department of the Russian Children’s Clinical Hospital. The analysis included patients with acquired and congenital forms of non-malignant diseases. The choice of an optimal unrelated donor in the absence of a compatible relative donor, as well as an analysis of the risks of treatment, requires studying the factors that influence the outcome of treatment in this group of patients. It was shown that the level of 2-year overall survival (OS) was 74 % (standard deviation ± 4.7 %). At the same time, clinical manifestations of the acute graft versus host disease of grade I–IV were recorded in 67 % (n = 66) of patients, and severe forms of grade III–IV in 13 % (n = 13) of children. Chronic graft versus host disease (chGVHD) was observed in 29 % (n = 29) patients. When studying the factors associated with the donor, it was found that the differences in the HLA system have a negative effect on the incidence of chGVHD; in a (9/10) HLA-incompatible donor, it was 29 % higher (p = 0.019). Increasing the age of the donor for every 10 years consistently reduces the OS by 9–11 % (p = 0.117), however, the OS with a donor over 46 years old was 100 % (n = 7). No effect on the agents with respect to the following factors with respect to the recipient was found: by sex, blood group, serostatus for cytomegalovirus (CMV). It was noted that the combination of CMV-positive serostatus of the donor and the negative status of the recipient increases the risk of transplant rejection up to 50 % in comparison with other variants of CMV serostatus (p = 0.001). In general, the possibility of performing HSCT from an unrelated donor for patients with non-malignant diseases and possible ways of selecting the optimal donor was noted. Conflict of interest. The authors declare no conflict of interest.Funding. The study was performed without external funding.

Tacrolimus Versus Cyclosporine for Graft-Versus-Host Disease Prophylaxis in Pediatric Patients Undergoing Matched Unrelated Donor Hematopoietic Stem Cell Transplants. A Pediatric Blood and Marrow Transplant Consortium Study..

Blood ◽  
2006 ◽  
Vol 108 (11) ◽  
pp. 2883-2883 ◽  
Author(s):  
Mark P. Atlas ◽  
Gregory Yanik ◽  
Rakesh Goyal
Keyword(s):  
Stem Cell ◽  
Hematopoietic Stem Cell ◽  
Graft Versus Host Disease ◽  
Acute Gvhd ◽  
Unrelated Donor ◽  
Matched Unrelated Donor ◽  
Hematopoietic Stem ◽  
Host Disease ◽  
Graft Versus Host ◽  
Grade Ii

Abstract Calcineurin inhibitors form the backbone of graft versus host disease (GVHD) prophylaxis in hematopoietic stem cell transplantation. In the adult literature tacrolimus was demonstrated superior to cyclosporine in preventing grade II–IV acute GVHD in both related and unrelated donor transplants; however, there is no data comparing their efficacy in the pediatric population. In a multi-institutional trial, we prospectively evaluated the clinical data on 102 patients receiving either cyclosporine/methotrexate or tacrolimus/methotrexate based prophylactic regimens for 6/6 matched unrelated donor, transplant. Conditioning regimens were fully ablative; no T-cell depletion was permitted; cord blood donors were excluded. Patients were required to receive either cyclosporine or tacrolimus, but the choice was per investigator preference. The two arms were reasonably balanced: 59.8% of patients received cyclosporine and 40.2% of patients received tacrolimus. Rates for maximum grade II–IV acute GVHD were 37.7% for cyclosporine and 39% for tacrolimus (p = 0.89). Rates for maximum grade III–IV acute GVHD were 19.6% for cyclosporine and 24.4% for tacrolimus (p = 0.57). Incidence of chronic GVHD in 97 evaluable patients was 37.9% in 58 patients who received cyclosporine and 35.8% in 39 patients who received tacrolimus (p = 0.84). Survival at 1 year post-transplant was similar in both groups: 59.2% for cyclosporine and 51.2% for tacrolimus (p= 0.31). Toxicity analysis is ongoing. In pediatric matched unrelated donor transplantation, the efficacy of tacrolimus/methotrexate and cyclosporine/methotrexate based regimens for prophylaxis of GVHD are not significantly different.

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