Donor Leukocyte Infusion after Stem Cell Transplantation in Patients with Juvenile Myelomonocytic Leukemia.

Blood ◽  
2004 ◽  
Vol 104 (11) ◽  
pp. 5001-5001
Author(s):  
Ayami Yoshimi ◽  
Peter Bader ◽  
Susanne Matthes-Martin ◽  
Jan Starý ◽  
Thomas Klingebiel ◽  
...  
Keyword(s):  
Stem Cell ◽  
Stem Cell Transplantation ◽  
Cell Transplantation ◽  
Acute Gvhd ◽  
Chronic Gvhd ◽  
Juvenile Myelomonocytic Leukemia ◽  
Donor Leukocyte Infusion ◽  
Matched Sibling ◽  
Myelomonocytic Leukemia ◽  
Relapse Group

Abstract Juvenile myelomonocytic leukemia (JMML) is a rare clonal disorder of early childhood. Currently, only allogeneic stem cell transplantation (SCT) offers long-term cure. Relapse remains the major cause of treatment failure. Although graft-versus-leukemia (GVL) effect most likely plays an important role in controlling JMML, the benefit of donor leukocyte infusion (DLI) following SCT in JMML is currently unknown. Patients and methods: Twenty-one patients with JMML who received DLI after SCT, including 4 patients after given a second SCT, were studied (BMT 14, PBSCT 6, CB 1). The median age at SCT was 15 (8–99) months. A normal karyotype, monosomy 7 or other aberrations were observed in 15, 2, and 4 patients, respectively. Six patients were transplanted from a matched sibling and 15 from an alternative donor. Chimerism analyses were performed by microsatellite PCR system or FISH for sex mismatch in all the patients. Response was defined as the achievement of complete chimerism (CC) and no evidence of hematological relapse. DLI was given either for the development of mixed chimerism (MC) in 7 patients (MC group) or for cytogenetic/hematological relapse in 14 patients (relapse group). Prior to DLI, cyclosporin A had been stopped in all patients, and no child had received chemotherapy. Results of DLI: Five of the 21 patients received a single DLI, 16 patients 2–6 infusions (median 3). The total T cell dose given ranged from 9x104 to 2.4 x108/kg. Six of 21 patients responded: 3 of 7 patients in the MC group and 3 of 14 patients in the relapse group. The infusion of at least 1x107/kg T cells was needed for durable response. Response was observed in all karyotype subgroups. None of the 6 patients receiving DLI from a matched sibling responded. Five patients developed acute GVHD following DLI and 4 of them responded to DLI. On the contrary, only 2 of the 16 children who did not show acute GVHD after DLI responded. Chronic GVHD developed in 2 responders. The outcome of even the responders was unfavorable. Only one of the responders is alive in remission, with severe chronic GVHD, 72 months after DLI. Two patients relapsed 26 days and 54 months after DLI (one as gastric chloroma), and 3 died of complications of DLI (acute GVHD, bone marrow aplasia, and hyper-eosinophilic syndrome). Four non-responders and one responder with subsequent relapse were rescued by a second SCT. Conclusion: This study shows that DLI can induce a GVL effect in some of the JMML patients. However, the benefit of DLI in our series of patients was limited because of severe complications in responders and lack of a durable effect. Some modification of DLI, with previous cytoreduction by chemotherapy or a novel drug such as E21R and concomitant administration of cytokines such as interferon alpha, can possibly improve the result of DLI.

Allogeneic Hematopoietic Stem Cell Transplantation for Children with Myelodysplastic Syndrome: A Report of a Korean Single Center Experience

Blood ◽  
2011 ◽  
Vol 118 (21) ◽  
pp. 4500-4500
Author(s):  
Jeong A. Park ◽  
Ho Joon Im ◽  
Jong Jin Seo
Keyword(s):  
Stem Cell ◽  
Stem Cell Transplantation ◽  
Cell Transplantation ◽  
Graft Failure ◽  
Acute Gvhd ◽  
Chronic Gvhd ◽  
Refractory Anemia ◽  
Hematopoietic Stem ◽  
Allogeneic Hsct ◽  
Matched Sibling

Abstract Abstract 4500 Purpose: Accounting for 4% of childhood hematological malignancy, myelodysplastic syndrome (MDS) is very rare in children than in adults. Therapy of these disorders has been associated with intensive treatment related toxicities and a high risk of relapse. Children with refractory anemia (RA)/refractory anemia with excess blast (RAEB) usually do not respond to acute myeloid leukemia (AML)- type chemotherapy, and chemotherapy without hematopoietic stem cell transplantation (HSCT) resulted in survival rates below 30%. Since failure rates after HSCT are lower in this group when treated at diagnosis, HSCT should be strongly considered, especially when a fully matched sibling donor (MSD) is available. The optimal treatment for children with RA/RAEB without matched sibling donor is presently undetermined. Some of them have stable disease course and require no therapy for years. However, aggressive treatment with HSCT using alternative donors should be considered for severe cytopenia. We analyzed the results of allogeneic HSCT in 16 children who were diagnosed with de novo MDS in a single Korean center. It is the first report about the outcome of HSCT for Pediatric MDS in Korea. Patients and Methods: Between November 1997 and June 2011, 16 children with MDS underwent allogeneic HSCT at Asan Medical Center. These patients had RA (n=7), and RAEB (n=9). Peripheral blood smears, bone marrow aspirates and biopsies of all patients were assessed by central morphology review according to the WHO classification. HSCT was recommended if the patients developed neutropenia (ANC<500/μ L) or transfusion dependency. Median age at transplant of 9 males and 7 females was 8.9 years (range 1.6–20.3). Cytogenetic analysis at diagnosis was available in 15 patients. Nine of them had a normal karyotype and 6 patients had miscellaneous chromosomal changes, but nobody had monosomy 7. Six patients (33%) were grafted from an MSD, whereas the remaining were transplanted from an unrelated donor (UD) (n=6), umbilical cord blood (n=3) or a haplo-identical family donor (n=1). All patients received myeloablative conditioning including busulfan (n=13) or total body irradiation (n=3). The median number of transfused CD34 cells was 8.2×106/kg for bone marrow or peripheral blood stem cell transplantation, and 1.3×105/kg for umbilical cord blood transplantation (UCBT). Graft-versus-host disease (GVHD) prophylaxis with cyclosporine and methotrexate was used for 14 patients, and cyclosporine and MMF were used for UCBT. Results: Sustained neutrophil engraftment was achieved in 11 patients, and five patients experienced graft failure. One patient died of subarachnoid hemorrhage on day 1 before engraftment, and 4 patients experienced primary graft failure; all patients were regrafted from haplo-identical related donors. Three patients are alive without disease, but one patient died 103 days after third HSCT from CMV pneumonia. The cumulative incidence of grade II-IV acute GVHD in the 15 evaluable patients was 0.27, and they were all manageable. Two patients developed extensive chronic GVHD; one patient died from disease progression to AML 579 days after HSCT, the other died from fungal pneumonia and intracranial hemorrhage 113 days after HSCT. With a median follow-up of 6.0 years (range 0.1–14), the cumulative incidence of treatment related mortality (TRM) and relapse was 0.19 and 0.20, respectively. The Kaplan-Meier estimates of overall survival (OS) and event free survival (EFS) at 5 years were 0.64 and 0.41. The diagnosis of RAEB was positively associated with relapse (P=0.02) and significantly decreased OS (P=0.024). Donor type was not significantly associated with TRM, graft failure, relapse and outcome. While acute GVHD did not affect the outcome, chronic GVHD significantly affected OS (P=0.0013). Conclusions: Though our results showed considerable early engraftment failure rates (31.3%), most of all were successfully regrafted form haplo-identical related donors, and showed comparable treatment outcome. Allogeneic HSCT following a myeloablative conditioning can offer a high probability of cure for children with MDS, however, efforts to further reduce the rejection, relapse and TRM in patients undergoing allogeneic HSCT are needed. Disclosures: No relevant conflicts of interest to declare.

Multicenter, Prospective Study of Tacrolimus Plus Methotrexate As Graft-Versus-Host Disease Prophylaxis in HLA-Matched Sibling Peripheral Blood Stem Cell Transplantation: Comparison with Cyclosporine Group As Control

Blood ◽  
2012 ◽  
Vol 120 (21) ◽  
pp. 4177-4177
Author(s):  
SeungHwan Shin ◽  
JaeHo Yoon ◽  
SeungAh Yahng ◽  
SungEun Lee ◽  
ByungSik Cho ◽  
...  
Keyword(s):  
Stem Cell ◽  
Stem Cell Transplantation ◽  
Cell Transplantation ◽  
Cumulative Incidence ◽  
Acute Gvhd ◽  
Chronic Gvhd ◽  
Hazard Ratio ◽  
Gvhd Prophylaxis ◽  
Matched Sibling ◽  
Grade Ii

Abstract Abstract 4177 Background Graft-versus-host disease (GVHD) is an immunologic complication after allogeneic hematopoietic stem cell transplantation (HSCT) with significant mortality and morbidities. Allogeneic peripheral blood stem cell transplantation (PBSCT) has high risk of GVHD, especially chronic GVHD compared to bone marrow transplantation. Only limited data are available comparing the efficacy of FK506 with that of cyclosporine (CsA) in human leukocyte antigen (HLA)-matched sibling PBSCT. Methods Thirty-nine patients with various hematologic disease received PBSCT with FK506+methotrexate (MTX) as GVHD prophylaxis were compared to ninety-four historical control with CsA+MTX GVHD prophylaxis. Results The 1-year cumulative incidence of grade II-IV acute GVHD was significantly lower in patients who received FK506 than those in the CsA group (10.3% vs 28.2%, p=0.036). The female donor-male recipient pair (hazard ratio; 4.828, 95% CI; 17.84-13.06, p=0.002) and CsA prophylaxis (hazard ratio; 3.279, 95% CI; 1.14–9.43, p=0.027) were significant risk factor of acute GVHD in multivariate analysis. But, there was no difference in the 3-year cumulative incidence of chronic GVHD between the FK506 and the CsA group (77.6% vs 69.6%, p=0.793). The 3-year cumulative incidence of relapse (33.9% vs 23.1%, p=0.505) and 3-year treatment-related mortality (18.9% vs 28.4%, p=0.187) of the two groups were similar. The patients in the FK506 arm had a similar event-free survival (EFS) and overall survival (OS) with patients in the CsA arm (3-year EFS; 53.2% vs 55.1%, p=0.706, 3-year OS; 60.7 vs 61.5%, p=0.610). The age over 35 years (hazard ratio; 4.12, 95% CI; 1.95–8.70, p=0.001), female donor-male recipient pair (hazard ratio; 2.66, 95% CI; 1.52–4.65, p=0.001) and advanced pre-HSCT disease status (hazard ratio; 3.13, 95% CI; 1.72–5.71, p=0.001) were significant prognostic factors associated with OS in multivariate analysis. Conclusion These results demonstrated that the FK506+MTX can significantly reduce grade II-IV acute GVHD compared to CsA+MTX in sibling PBSCT with similar incidence of chronic GVHD, and comparable outcome in EFS, OS, relapse rate and TRM rate between two groups. Disclosures: No relevant conflicts of interest to declare.

Haploidentical non-myeloablative stem cell transplantation as Salvage for graft failure in a patient with juvenile myelomonocytic leukemia

2011 ◽  
Vol 57 (6) ◽  
pp. 1084-1084
Author(s):  
Guilherme F. Perini ◽  
Fábio R. Kerbauy ◽  
Juliana Folloni Fernandes ◽  
Fábio Pires S. Santos ◽  
Margareth A. Torres ◽  
...  
Keyword(s):  
Stem Cell ◽  
Stem Cell Transplantation ◽  
Cell Transplantation ◽  
Graft Failure ◽  
Juvenile Myelomonocytic Leukemia ◽  
Myelomonocytic Leukemia

Durable Remission after Prophylactic Donor Lymphocyte Transfusion Following Allogeneic Stem Cell Transplantation with Reduced Conditioning for High-Risk AML and MDS.

Blood ◽  
2004 ◽  
Vol 104 (11) ◽  
pp. 299-299
Author(s):  
Michael Schleuning ◽  
Christoph Schmid ◽  
Georg Ledderose ◽  
Johanna Tischer ◽  
Meike Humann ◽  
...  
Keyword(s):  
Stem Cell ◽  
High Risk ◽  
Stem Cell Transplantation ◽  
Cell Transplantation ◽  
Allogeneic Stem Cell Transplantation ◽  
Acute Gvhd ◽  
Chronic Gvhd ◽  
Allogeneic Transplantation ◽  
Chronic Infections ◽  
Term Survival

Abstract Prophylactic transfusion of donor lymphocytes (pDLT) is an attractive form of maintenance therapy after allogeneic stem cell transplantation in patients with high risk of relapse. However, clinical experience is limited, and disease response is often achieved at the expense of severe graft-versus-host disease (GvHD). We here report our data on pDLT in high-risk AML and MDS. Cells were given within a prospective protocol that contained a sequence of chemotherapy, reduced intensity conditioning for allogeneic transplantation, and pDLT (FLAMSA-regimen). For pDLT, patients had to be in CR at least 120 days from transplantation, off immunosuppression for 30 days, and free of GvHD. 22/86 patients alive at day +120 fulfilled the criteria for pDLT. They had been transplanted for refractory or relapsed leukemia (n=9 each) or in CR1 because of unfavorable cytogenetics (n=4). 14 patients had an unfavorable karyotype, 8 with complex aberrations. Reasons for withholding pDLT in 64 patients included cGvHD or prolonged immunosuppression (n=38), refractory or relapsed leukemia (n=15), refusal of patient or donor (n=4 each), a history of grade IV acute GvHD (n=2), and chronic infections (n=3). The median time from transplant to first pDLT was 167 days (range 120–297). Median follow up of transfused patients is 696 days (range 209–1341). Ten patients received 1, 6 patients received 2, and 6 patients received 3 transfusions in escalating doses, containing a median of 1x106, 5x106 and 1x107 CD3+ cells/kg at pDLT 1, 2 and 3, respectively. Reasons for giving less than 3 transfusions were GvHD, relapse or refusal of the patient. Induction of GvHD was the main complication; grade III acute GvHD developed in 1, and chronic GvHD in 7 patients. So far, 5 patients have relapsed despite pDLT. One died of refractory leukemia, whereas 2 achieved secondary CR following adoptive immunotherapy. Two patients are currently under treatment. At present, 18/22 patients are alive and in CR at a median of 423 days post DLT. The current leukemia free survival at two years from first pDLT is 79%. Nineteen patients were complete chimeras at time of pDLT. pDLT converted mixed into complete bone marrow chimerism in 1, but failed in 2 cases. In our experience, pDLT is safe after allogeneic transplantation for high risk AML, when given at low doses and to a selected group of patients. Results are encouraging, and long term survival can be achieved. However, further studies need to define more precisely the contribution of pDLT to the therapeutic effect of the entire procedure.

Effect of Rituximab on the Incidence of GVHD in Lymphoma Patients who Received the BEAM-Conditioning and an Allogeneic Stem Cell Transplantation.

Blood ◽  
2004 ◽  
Vol 104 (11) ◽  
pp. 4980-4980
Author(s):  
Issa F. Khouri ◽  
Rima M. Saliba ◽  
Daniel R. Couriel ◽  
Grace-Julia Okoroji ◽  
Sandra Acholonu ◽  
...  
Keyword(s):  
Stem Cell ◽  
B Cells ◽  
Stem Cell Transplantation ◽  
Cell Transplantation ◽  
Allogeneic Stem Cell Transplantation ◽  
Acute Gvhd ◽  
Chronic Gvhd ◽  
Conditioning Regimen ◽  
Control Group ◽  
Study Group

Abstract It has been postulated that B cells functioning as antigen-presenting cells may have an important role in the pathogenesis of GVHD. Depletion of donor cells from B-cells resulted in a low incidence of GVHD in mouse model (Schultz et al. BMT1995:16:289–289). More recently, we observed a lower incidence of chronic (and to a lesser extent acute GVHD) in patients with CLL who received an allogeneic stem cell transplantation after a non-myeloablative conditioning regimen containing rituximab (Exp Hematol32:28–35, 2004). The purpose of this study is to investigate the effect of rituximab on GVHD in the setting of a more intense chemotherapy with BEAM, in patients who received an allogeneic peripheral blood stem cell from HLA-identical siblings. To test this hypothesis, we retrospectively studied 11 consecutive patients with non-Hodgkin’s lymphoma who received BEAM/Rituximab at the M. D. Anderson Cancer Center. We attempted to match these patients by age, donor-recipient gender, and donor-recipient CMV reactivity to a historical control of 44 patients with lymphoma, who received BEAM alone as a conditioning regimen, without the Rituximab. Tacrolimus and methotrexate were used for GVHD prophylaxis in both groups. A total of 10 patients in the study group, could be matched with 19 patients in the control group and were included in the final analysis. The outcome of the 2 groups is shown below: Rituximab-Study Group Control Group -value P No. of patients 10 19 Median age 41 44 0.4     (range) (19–55) (19–60) Patient-Donor sex-matched 9(82%) 18(95%) 0.6 Median # CD34 + cells infused (106/kg) 5.1 4.73 0.1 Patient or Donor CMV+ 9(82%) 18(95%) 0.6 Patient and Donor CMV − 1(10%) 1(5%) Median # prior chemoregimens 3 3 0.9     range (1–8) (1–9) Median follow-up 17 38     range (8–48) (27–77) Acute GVHD 2–4 (n,%) 5(50%) 7(37%) 0.5 Acute GVHD 3–4 (n,%) 3(30%) 5(26%) 0.6 Chronic GVHD (n, % cumulative incidence) 8 (90% + 15) 10 (53% + 12 0.01 Our data suggest that the described protective effect of Rituximab against GVHD in mouse models or in the setting of non-myeloablative allogeneic transplantation, may be overcome by the BEAM. This more intense conditioning regimen may induce more GVHD by enhancing T-cell cytokines release and by causing more gastrointestinal toxicity, thus allowing for a greater antigen presentation.

Rapid Cyclosporine Tapering and Isotretinoin Usage after Unrelated Donor Hematopoietic Stem Cell Transplantation in Juvenile Myelomonocytic Leukemia.

Blood ◽  
2004 ◽  
Vol 104 (11) ◽  
pp. 5188-5188
Author(s):  
Keon Hee Yoo ◽  
Soo Hyun Lee ◽  
Ki Woong Sung ◽  
Hong Hoe Koo ◽  
Hye Lim Jung
Keyword(s):  
Stem Cell ◽  
Hematopoietic Stem Cell Transplantation ◽  
Complete Remission ◽  
Stem Cell Transplantation ◽  
Acute Gvhd ◽  
Juvenile Myelomonocytic Leukemia ◽  
Hematopoietic Stem ◽  
Differentiating Agent ◽  
Myelomonocytic Leukemia ◽  
Disease Free

Abstract Juvenile myelomonocytic leukemia (JMML) is a rare type of childhood leukemias, and allogeneic hematopoietic stem cell transplantation (HSCT) is known to be the only way to cure the disease. Unfortunately, relapse is still the most frequent cause of treatment failure after transplant in JMML. We investigated the feasibility of inducing graft versus leukemia (GVL) effect and the use of a differentiating agent even after unrelated HSCT in children with JMML. Seven consecutive patients with JMML underwent unrelated HSCT at a median age of 17 months. The sources of grafts were bone marrows (n=3) or HLA 1- or 2-antigen mismatched cord bloods (n=4). Only 3 of the 7 patients were in complete remission before transplantation. Intravenous busulfan, cyclophosphamide, and etoposide were used as preparative agents except in one who was conditioned with TBI-based regimen. Cyclosporine was used universally for GVHD prophylaxis with additional use of short-term methotrexate in bone marrow transplants and of methyl-prednisolone in cord blood transplants. Cyclosporine was tapered rapidly from around 1 month post-HSCT and isotretinoin (75–100 mg/m2/day) was used in selected patients who have any risk factors of relapse. Cyclosporine blood levels were 247.8±91.1, 146.6±104.2, and 88.8±52.6 ng/mL at 1, 2, and 3 months post-transplant, respectively. There was no grade 3 or 4 acute GVHD and only 2 patients developed grade 2 acute GVHD which was improved without additional treatment. Chronic GVHD was developed in 3 (1 limited, 2 extensive) of the evaluable 5 patents, which was all resolved after combined use of immune suppressive agents. Initial chimeric status analysis at 1 month revealed complete donor chimerism (CC) in 4 patients, mixed chimerism (MC) in 2 and autologous recovery (AR) in one. One of the patients with MC and the one with AR were in disease-free status. One patient whose chimeric status changed from CC to MC eventually relapsed. One patient with initial MC with residual disease turned to CC with complete remission. Another patient with initial MC but with no evidence of disease is on treatment with isotretinoin without relapse for 3 months even with persistent MC. The patient with AR relapsed early after transplant. Five patients are alive relapse-free and disease-free with a median follow-up of 16 months after transplant. The Kaplan-Meier probability of event-free survival was 66.7%. We suggest that GVL induction strategy with concomittant use of a differentiating agent might have a role to suppress leukemic relapse in JMML.

The Effect of Costimulatory Moleculars on Graft-Versus-Host Disease after Allogeneic Hematopoietic Stem Cell Transplantation.

Blood ◽  
2007 ◽  
Vol 110 (11) ◽  
pp. 4875-4875
Author(s):  
Zhenhua Qiao ◽  
Fang Ye ◽  
Lei Zu
Keyword(s):  
Stem Cell ◽  
T Cell ◽  
Stem Cell Transplantation ◽  
Cell Transplantation ◽  
Acute Gvhd ◽  
Chronic Gvhd ◽  
Hematopoietic Stem ◽  
Graft Versus Host ◽  
Group A ◽  
Group B

Abstract Objective: To explore the effect of costimulatory molecular and CD25 expressed on peripheral CD4+ T lymphocytes on graft-versus-host disease(GVHD) after allogeneic hematopoietic stem cell transplantation(allo-HSCT). Methods: 1. The 21 patients who suffered of hematology diseases or malignant solid tumors and were underwent allo-HSCT and 10 normal individuals were enrolled in the study.2. For the sake of difference conditioning regimens we divided the 21 patients into two groups: patients undergoing non-myeloablative stem cell transplantation(NST) belonged to group A, others undergoing traditional myeloablative stem cell transplantation belonged to group B; we divided them into five groups for with GVHD or without GVHD and types of GVHD: group 1(group A with acute GVHD), group 2(group A with chronic GVHD), group 3(group B with acute GVHD), group 4(group B without GVHD), group 5(group A without GVHD).3. The levels of CD28, CD80, CD152 and CD25 expressions on peripheral CD4+ T lymphocytes were detected by three colors flow cytometry (FCM)in different time(before allo-HSCT,7days,14days,21days,30days after allo-HSCT, the time of GVHD and the time after GVHD treated).4.STR-PCR for detecting micro-satellites chimeras forming. Results: 1. All 21 patients achieved engraftment. By STR-PCR assay,12 cases formed complete chimeras(CC) and 9 cases formed mixed chimeras(MC). In group A,3 cases developed acute GVHD and 4 cases developed chronic GVHD; in group B,4 cases developed aGVHD. The incidence of GVHD and infection rates between group A and B has no difference(X2=3.711, P=0.144).2. Among these 21 cases,5 cases died:2 cases died of multiple organs function failure due to primary disease relapse,1 case died of bleeding in brain and 2 cases died of liver function failure for the sake of complicated with acute GVHD; others survive with disease free till present.3. The results of multivariate logistic regression models and Kaplan-Meier survival curves analyses showed: age, sex, infection, HLA-type, blood type, conditioning regiment and the times of absolute neutrophil counts and platelets recovering to normal, had no association with the incidence of GVHD;A multivariate COX survival function model analysis showed CD4CD152 and CD4CD25 are independent prognostic factors for GVHD(X2=13.128, P<0.0001).4. Patients with GVHD demonstrated higher CD4+CD28+ and CD4+CD80+ T cell levels than those without GVHD(P<0.01);patients with aGVHD demonstrated higher than those with cGVHD(P<0.05) and without GVHD(P<0.05); Patients with GVHD demonstrated lower CD4+CD152+ and CD4+CD25+ T cell levels than those without GVHD(P<0.01); the same result occurs between aGVHD and cGVHD and without GVHD. After effective treatment, unnormal CD4+CD28+, CD4+CD80+, CD4+CD152+ and CD4+CD25+ T cell levels recovered to the levels before transplantation. Conclusions: The incidences of GVHD between NST and traditional myeloablative stem cell transplantation had no difference. B7-CD28/CD152 costimulatory pathway plays a critical role in developing of GVHD. Peripheral CD4+CD28+, CD4+CD80+, CD4+CD152+ and CD4+CD25+ T cell levels were relative to recipient GVHD, especially CD4+CD152+ and CD4+CD25+ T cell levels. Down-grade CD4+CD28+ and CD4+CD80+ T cell levels and up-grade CD4+CD152+ and CD4+CD25+T cell levels could reduce the incidence of GVHD.

Evaluation of NIH Consensus Criteria for Classification of Late Acute and Chronic Gvhd in Reduce Intensity Conditioning (RIC) Stem Cell Transplantation (SCT).

Blood ◽  
2009 ◽  
Vol 114 (22) ◽  
pp. 1139-1139 ◽  
Author(s):  
Jifang Zhou ◽  
Sylvain Thepot ◽  
Aurrore Perrot ◽  
Marie Robin ◽  
Regis Peffault de Latour ◽  
...  
Keyword(s):  
Stem Cell ◽  
Stem Cell Transplantation ◽  
Cell Transplantation ◽  
Cumulative Incidence ◽  
Acute Gvhd ◽  
Late Onset ◽  
Chronic Gvhd ◽  
Time Dependent ◽  
Increased Risk ◽  
Nih Consensus Criteria

Abstract Abstract 1139 Poster Board I-161 Background Chronic graft-versus-host disease (GVHD) occurs frequently after allogeneic stem cell transplantation (SCT) and has an impact on morbidity and survival. The National Institutes of Heath (NIH) consensus criteria for the diagnosis of GVHD, emphasized clinical manifestations of GVHD rather than the classical time of onset (day 100). Incidence and impact in term of relapse and no-relapse mortality (NRM) of this new classification is not well known after RIC. Methods We retrospectively reviewed 116 consecutive patients (pts) in Saint Louis' Hospital undergoing an SCT for hematologic malignancy and surviving at least day + 100 after RIC between August 2005 and December 2008. We evaluated non-relapse mortality (NRM) and recurrent malignancy. Cumulative incidence was computed using death as a competing event. Incidence of relapse and NRM was counted from 100 days post-transplant for patients without chronic GVHD or from chronic GVHD onset. Patients with relapse/progression before chronic GVHD onset were considered as not having chronic GVHD in these analyses. The association of occurrence of chronic GVHD with the risk of relapse and non-relapse death was analyzed using time-dependent covariates in cause-specific proportional hazards models. Results Among 116 pts ( M/F: 71/45), with a median age of 53 years old (19-68 years) 28 pts (24%) were transplanted for acute leukemia in, 11 pts (9%) for chronic leukemia, 27 pts (23%) for lymphoma, 30 pts (26%) for MPD/MDS and 20 pts (17%) for plasma cell disorder. Sixty-three pts (54%) received HLA-identical sibling transplantation, 53 pts (46%) received transplantation from unrelated donors. Source of stem cells was mobilized peripheral blood stem cell for 108 pts (93%), bone marrow for 4 pts (3%) and 4 cord blood (3%). After a median follow-up of 18 months (range 5-45 months), a total of 67 pts (58%) developed chronic GVHD according to the Seattle day 100 landmark criteria and when using NIH consensus criteria, 55 pts (47%) developed chronic GVHD, including 43 pts (53%) with classic chronic GVHD and 8 pts (10%) overlap syndrome. Patients reclassified included; 3 pts with late onset acute GvHD, 19 pts had recurrent and 8 had persistent acute GVHD (numbers do not to previous sentence because some of these patients latter developed chronic GvHD). The cumulative incidence of chronic GVHD at 36 months was 64% (95%CI; 53%-73%) when using Seattle criteria compared to 56% (95%CI; 45%-67%) with NIH chronic GVHD criteria. Two-year Cumulative incidences of relapse and NRM using both classifications are summarized in Table. In Cox model with GvHD as a time dependent covariate, the NRM was significantly higher in patients with late onset, persistent and recurrent acute GVHD compared to no GVHD (hazard ratio (HR) 31, 47 and 30; p = 0.005, p <0.0001, p <0.0001, respectively), whereas the NRM was statistically increased in case of chronic GVHD using Seattle day 100 criteria (HR: 2.8; P=0.034). Conclusion The cumulative incidence of chronic GVHD “decrease” about 10% when using NIH consensus criteria compared to Seattle criteria in our cohort of RIC. Most of the NRM occurred beyond 100 days after SCT was due to the increased risk of NRM in patients with late onset, recurrent or persistent acute GVHD. Disclosures No relevant conflicts of interest to declare.

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