ZAP-70 Expression and Stem Cell Transplantation Results in Patients with CLL.

Blood ◽  
2006 ◽  
Vol 108 (11) ◽  
pp. 3670-3670
Author(s):  
Neus Villamor ◽  
Olga Salamero ◽  
Jordi Esteve ◽  
Joaquim Carreras ◽  
Carol Moreno ◽  
...  
Keyword(s):  
Stem Cell ◽  
Stem Cell Transplantation ◽  
Cell Transplantation ◽  
Relapse Rate ◽  
Negative Impact ◽  
Disease Free Survival ◽  
Leukemic Cells ◽  
Free Survival ◽  
Vh Gene

Abstract The absence of mutations in the VH gene (UM-VH) and the expression of ZAP-70 by leukemic cells are closely related adverse prognostic factors in CLL. Whether ZAP-70 should substitute VH gene analysis as prognostic predictor in patients with CLL is a matter of debate. We and others have shown that allogeneic but not autologous stem-cell transplantation may overcome the negative impact of the UM-VH on the outcome of patients with CLL. Herein we report on transplantation results based on ZAP-70 expression in leukemic cells. Thirty-seven patients (24 M/13 F; median age: 48 years, range: 29-63) received either an autologous (auto-SCT) (n=22) or an allogeneic (allo-SCT) (n=15) transplant. ZAP-70 was assessed by flow cytometry (19 cases), lymph node immunohistochemistry (10 cases) or both (8 cases). No discrepancies were observed in those cases in which both peripheral blood and lymph nodes were analyzed. Thirty-one patients were ZAP-70 positive and 6 ZAP-70 negative. ZAP-70 was positive in all UM-VH (n=24) and in 4 of 8 mutated VH patients. After a median follow-up of 62 months (range: 4 – 142), 5-year survival is 86% (66% to 100%) for allo-SCT and 50% (28% to 72%) for auto-SCT (p=NS), whereas 5-year disease-free survival (DFS) is 80% (54% to 100%) for allo-SCT and 37% (15% to 59%) for auto-SCT (p=0.03). Seventeen patients have relapsed: 16 of 31 of those being ZAP-70 positive and 1 of 6 of those ZAP-70 negative. In ZAP-70 positive patients the cumulative relapse rate at 5 years is 10% (2% to 65%) in the allo-SCT group and 53% (35% to 81%) in the auto-SCT group (p=0.04) (figure 1a). In addition, ZAP-70 positive patients submitted to allo-SCT have a trend for a longer DFS (76% at 5 years; 46% to 100%) than those receiving an auto-SCT (39% at 5 years; 15% to 63%) (p=0.07) (figure 1b). In summary, among transplanted patients those with ZAP-70 positive CLL have a better relapse rate and DFS if submitted to allo-SCT. Figure Figure

Autologous Stem Cell Transplantation (ASCT) for Enteropathy-Associated T-Cell Lymphoma (EATCL): A Retrospective Study of the European Group for Blood and Marrow Transplantation (EBMT)

Blood ◽  
2011 ◽  
Vol 118 (21) ◽  
pp. 3115-3115
Author(s):  
Esa Jantunen ◽  
Ariane Boumendil ◽  
Alessandro Rambaldi ◽  
Marc Schapira ◽  
Jian Jian Luan ◽  
...  
Keyword(s):  
Overall Survival ◽  
Stem Cell ◽  
Stem Cell Transplantation ◽  
Cell Transplantation ◽  
Cell Lymphoma ◽  
Disease Free Survival ◽  
Free Survival ◽  
History Of ◽  
Disease Free

Abstract Abstract 3115 Background: EATCL is a rare subtype of peripheral T-cell lymphoma frequently observed in patients with a history of celiac disease. EATCL is characterized by poor prognosis when treated with conventional chemotherapy with only 10–20 % of long-term survivors. Limited data are available on feasibility and efficacy of stem cell transplantation in this lymphoma entity. Patients and methods: The database of the EBMT was used to identify patients with EATCL who had received autologous and/or allogeneic stem cell transplantation in 2000–2007. All centres reporting these patients were contacted to receive confirmation to histopathology report/pathology review and to obtain information in regard to treatment prior to stem cell transplantation and more recent follow-up data. Results: Altogether 85 patients with EATCL were identified. Seventy-three patients had received ASCT and 12 patients allogeneic SCT. Histological report/review with additional follow-up data was available from 22 ASCT treated patients which are reported here. There were 14 females (64 %) and eight males with a median age of 55 years at the time of transplant. Half of the patients had a history of coeliac disease. The median number of treatment lines before ASCT was 1 and 50 % of the patients were in the first remission at the time of ASCT. BEAM was the most commonly used high-dose regimen (17 pts, 77 %) and all patents received blood stem cell grafts. The median time from the diagnosis to ASCT was 6 months. The median follow-up time for living patients was 45 months from ASCT. During the follow-up relapse has been observed in 13 patients (59 %), the median time was only four months from ASCT. The median disease-free survival and overall survival were nine months and 15 months, respectively. Two-year overall survival, disease-free survival, cumulative incidence of relapse and non-relase mortality (NRM) was 45%, 40%, 55% and 4%, respectively. Conclusions: ASCT is feasible in selected patients with EATCL with a low NRM. Of transplanted patients 40 % remained disease-free beyond 2 years. This seems to be superior when compared to historical experiences although selection factors should be taken into account. ASCT is a treatment option in transplant eligible EATCL patients who respond to initial therapy. Disclosures: No relevant conflicts of interest to declare.

scholarly journals A Novel Therapy Protocol Improves Outcomes of Hematopoietic Stem Cell Transplantation in Juvenile Myelomonocytic Leukemia Patients Using Hypomethylation of Decitabine

Blood ◽  
2018 ◽  
Vol 132 (Supplement 1) ◽  
pp. 5778-5778
Author(s):  
Zhiyong Peng ◽  
Xiaoqin Feng ◽  
Huaying Liu ◽  
Yuelin He ◽  
Jianyun Liao ◽  
...  
Keyword(s):  
Stem Cell ◽  
Stem Cell Transplantation ◽  
Cell Transplantation ◽  
Disease Free Survival ◽  
Juvenile Myelomonocytic Leukemia ◽  
Hematopoietic Stem ◽  
Free Survival ◽  
Post Transplant ◽  
Myelomonocytic Leukemia

Abstract Background Juvenile myelomonocytic leukemia(JMML) has usually poor response to chemotherapy, and approximately 50% of patients relapse after hematopoietic stem cell transplantation (HSCT). Recent studies have highlighted the importance of epigenetic aberrations in JMML and proved that some JMML stem cells were associated with hypermethylation. Hence, we desiged the current study to investigate whether low dose Decitabine could improve outcomes of JMML-HSCT.We have reported the preliminary results of low-dose decitabine in the treatment of children with JMML in 2017 ASH as a poster(see blood 2017 130:3232). Then, we will report our latest study. Patients and method 27 patients received HSCT combined with Decitabine between December 2014 and July 2018. Of them,6 patients with NF-1 mutation,11 with PTPN11 mutation, 2 with Kras somatic mutation ,1 with Nras somatic mutation, 3 with multiple mutation (PTPN11+NF-1),2 with monosomy 7,and 3 with uncertain mutation. The median age at diagnosis was 24 months (range: 1-72 months). 26/27 patients received 1~4 course mild chemotherapy(one patient,case 6, received only single course Decitabine therapy)before HSCT.3 patients received HSCT from HLA matched unrelated donors(MUD),and 24 patients received the complementary transplantation(CT), i.e. unrelated cord blood(UCB) was given at day 6 after haploidentical peripheral blood stem cell transplantation(PBSCT) using high dose cyclophosphamide(Cy) post-transplant (PTCy), (see blood 2016 128:1235). Conditioning regimen was composed of Cy, Busulfan (Bu)/ Thiotepa (TT), Fludarabine (Flu) and ATG-F in the MUD-HSCT, and Cy, Bu/TT, Flu and Cytarabine in the CT. Patients received a fixed dose of 8×108/kg mononuclear cells(MNC) in the MUD-HSCT, and a median dose of 45.5×108/kg (range, 26.8~88×108/kg) mobilized peripheral blood MNCs and a median dose of 8.9×107/kg (range, 4.0~12.8×107/kg) UCB nucleated cells in the CT, respectively. GVHD prophylaxis consisted of PTCy, Mycophenolate Mofetil (MMF) and Tacrolimus in the CT, and Thymoglobuline, CsA and MMF in the MUD-HSCT. Decitabine was administrated for 2~4 courses (20mg/m2.d×5 day for each course with 4-week interval) before HSCT to reduce load of leukemia cells and for 2~4 courses (5~10mg/m2.day×5day for each course with the interval of 4~6 weeks) after HSCT to overcome immune-escape of leukemia cells. Results: The median follow-up time was 13months (range, 2-51 months). Full donor cells were engrafted in all patients (donor cell engraftment in case 6 occurred in a salvaged transplant from another haplo-donor after primary failure of first CT).The Overall survival(OS) and Disease-free survival(DFS) was 89.4% and 87.3% respectively. In the CT, haplo-cells and UCB-cells were engrafted in 10 and 14 patients, respectively. The median time to neutrophil more than 0.5x109/L was 31days (range,12~71 days) and 17 days (range, 12~35 days)post-transplant, and to platelet more than 20 x109/L was 22 days (range,9~105 days) and 12 days (range,10~30 days) post-transplant, respectively, in the CT and the MUD- HSCT. All the 3 patients with relapse were haploid-engrated. Two of the three patients with relapse had underwent secondary CT. One of them was Disease-free survival ,and the other died of viral encephalitis(HHV-6) after secondary CT. The cumulative incidence of grades Ⅱ-Ⅳ acute GVHD (aGVHD) was 25.9% (7/27 patients). Case 6 had grade III aGVHD. A case died of grade IV aGVHD(gut) 50 days after the CT. Chronic GVHD(cGVHD) occurred in 5 patients, and no cGVHD more than grade II (NIH criterion) occurred in all patients. The most common complication associated with HSCT was infection. The cumulative incidences of infection plus reactivation of CMV,EBV and HHV-6 were 30% (7/27),3.7%(1/27) and 11.1%(3/27), respectively. Recoverable serious pancytopenia occurred in 3 patients with Decitabine therapy post-HSCT. Conclusion: The combination of hypomethylation agent with HSCT still showed satisfactory results in JMML-HSCT when the follow-up time has been extended for one year. A large-cohort study with extending follow-up time should be developed continuously in the future and the interim results of five-year follow-up time will be reported. Disclosures No relevant conflicts of interest to declare.

scholarly journals Autologous Hematopoietic Stem Cell Transplantation for Refractory Lupus Nephritis

2019 ◽  
Vol 14 (5) ◽  
pp. 719-727 ◽  
Author(s):  
Xianghua Huang ◽  
Wencui Chen ◽  
Guisheng Ren ◽  
Liang Zhao ◽  
Jinzhou Guo ◽  
...  
Keyword(s):  
Stem Cell ◽  
Hematopoietic Stem Cell Transplantation ◽  
Lupus Nephritis ◽  
Stem Cell Transplantation ◽  
Cell Transplantation ◽  
Hematopoietic Stem Cell ◽  
Disease Free Survival ◽  
Cell Transplant ◽  
Hematopoietic Stem

Background and objectivesOur study evaluated the efficiency and safety of autologous hematopoietic stem cell transplantation treatment for patients with refractory lupus nephritis.Design, setting, participants, & measurementsFrom July 2011 to January 2015, a total of 22 patients with refractory lupus nephritis were enrolled in this study. Peripheral blood stem cells were mobilized with cyclophosphamide and granulocyte colony stimulating factor and reinfused after treatment with cyclophosphamide and antithymocyte globulin. The primary end point was the rate of remission, and secondary end points included the survival and relapse rates, changes in proteinuria, kidney function, and serology immunologic test. All complications were recorded for safety assessment.ResultsTwenty-two patients were enrolled and underwent stem cell mobilization. There were nine men and 13 women, with a median lupus nephritis duration of 46 (33–71) months. The mean number of CD34+ cells was (7.3±3.8)×106/kg. All patients had successful engraftment, and the median times of granulocyte and platelet engraftment were 8 (7–9) and 9 (6–10) days, respectively. The major complications of stem cell transplantation were fever and gastrointestinal tract symptoms. The treatment-related mortality was 5% (one of 22). After a median follow-up of 72 (60–80) months, 18 (82%) patients achieved completed remission, one (5%) patient achieved partial remission, and one patient had no response and received peritoneal dialysis at 12 months after transplantation. The 5-year overall survival and disease-free survival rates were 91% and 53%, respectively. Six patients experienced relapse during the follow-up, and the relapse rate was 27%.ConclusionsAutologous hematopoietic stem cell transplant could be used as a treatment option for refractory lupus nephritis, because it was relatively safe and associated with good outcomes.

Rituximab and Stem Cell Transplantation Produces Durable Remissions in Mantle Cell Lymphoma.

Blood ◽  
2004 ◽  
Vol 104 (11) ◽  
pp. 1390-1390
Author(s):  
Francisco J. Capote ◽  
M. J. Pascual ◽  
E. Gonzalez-Barca ◽  
J. M. Bergua ◽  
A. Jimenez ◽  
...  
Keyword(s):  
Stem Cell ◽  
Complete Remission ◽  
Stem Cell Transplantation ◽  
Mantle Cell Lymphoma ◽  
Cell Transplantation ◽  
Cell Lymphoma ◽  
High Dose ◽  
Free Survival ◽  
Mantle Cell

Abstract Introduction: Mantle cell lymphoma (MCL) is a CD20+ malignancy comprising up 5% of non-Hodgkin’s lymphomas, and has a poor prognosis under standard chemotherapy. The HyperCVAD-M/A regimen (fractionated high-dose cyclophosphamide, vincristine, doxorubicin and prednisolone alternated with methotraxate and cytarabine) has yielded encouraging results when combined with autologous stem cell transplantation (ASCT) in MCL, with 5-year failure-free survival of 54% and overall survival 72%. In an effort to improve these results further, we have combined rituximab in vivo purging and post-transplant consolidation with HyperCVAD-M/A plus ASCT. Methods: Patients aged <65 years with previously untreated or relapsed MCL were treated with four courses of HyperCVAD-M/A followed by four once-weekly doses of rituximab 375mg/m2 as purging prior to stem cell mobilization and harvesting, high-dose chemotherapy (ICT-CY or BEAM), stem cell reinfusion and four further doses of rituximab immunotherapy post-transplant. Results: Of the 34 patients enrolled so far, 15 (12 male, 3 female; 12 previously untreated) have been transplanted. The median age was 52 years (range 47–63 years). After the final post-ASCT immunotherapy all 15 patients were in clinical complete remission. With a median follow-up of 30 months from diagnosis (range 7–52 months), 14 patients remain alive with 13 in first complete remission. One patient died 15 months post-ASCT without evidence of disease recurrence. Kaplan-Meier estimates of 4-year overall and event-free survival are 93.3% and 86.6% respectively. Conclusions: This approach seems safe and feasible and produces durable remissions; longer follow-up of a more patients will be required to assess the effect of the procedure on survival.

Radiotherapy Post Autologous Stem Cell Transplantation in Patients with Lymphoma Not Reached Complete Response.

Blood ◽  
2005 ◽  
Vol 106 (11) ◽  
pp. 5473-5473
Author(s):  
Naibai Chang ◽  
Xichun Gu ◽  
Ling Zhu ◽  
Jianping Wei ◽  
Shengming Zhao ◽  
...  
Keyword(s):  
Overall Survival ◽  
Stem Cell ◽  
Stem Cell Transplantation ◽  
Cell Transplantation ◽  
Autologous Stem Cell Transplantation ◽  
Disease Free Survival ◽  
Complete Response ◽  
Hematologic Toxicity ◽  
Free Survival ◽  
Disease Free

Abstract Objective: Anthracycline-based chemotherapy induces 50%–70% of CR in patients with lymphoma, but only 30%–40% of long-term disease-free survival. Salvage chemotherapy with autologous stem cell rescue is required in patients with aggressive disease or never achieve CR with conventional chemotherapy,but the relapsed rate is still high. The purpose of this study was to evaluate radiotherapy post autologous stem cell transplantation in such group of patients. Methods: 15 patients who underwent autologous stem cell transplantation during 1992–1998 were enrolled in this study. Conditioning regimen was CBV (cyclophosphomide + carmustine + etoposide). Radiotherapy was started on day +50(31–90). All patients were followed up until January 2005. Kaplan-Mier survival analysis was made by using SPSS10.0 software. Results: There were 14 patients with non-Hodgkin lymphoma and 1 with Hodgkin disease enrolled. Male:female=11:4. Median age was 40 (30–64). At least 6 cycles of induction chemotherapy were given before transplantation. There were 3 patients in progression disease, 1 in stable disease, and 11 in partial remission before transplantation. Three patients received total lymph node irradiation (TLI). Seven patients received TBI(200cGY)+involved field irradiation therapy(IFIT). Five were treated with IFIT. All patients acheaved complete response(including 1 CRu) after radiotherapy. Three patients relapsed. One patient treated with TBI+IFIT relapsed at 6 months later. Two patients treated with IFIT relapsed at 8 and 36 months later respectively. The mean disease-free survival and overall survival were 10.84(SD1.37,95%CI) years and 11.89(SD1.35,95%CI) years respectively. The estimatrd 10-year disease-free survival and Overall survival were both 73%. One patient developed AML at 86 month. Grade III–IV hematologic toxicity was seen in 2 patients. Conclusions: Post ASCT radiotherapy is safe and tolerated. Relaps rate is low. Patients who received TLI or TBI+IFIT seem to have better outcome than that received IFIT only.

Front-Line Consolidation with Autologous Stem Cell Transplantation in Patients with Nodal Aggressive Peripheral T-Cell Lymphoma (PTCL). A Prospective Study of the GEL-TAMO.

Blood ◽  
2006 ◽  
Vol 108 (11) ◽  
pp. 2463-2463
Author(s):  
Jose Rodriguez ◽  
Eulogio Conde ◽  
Antonio Gutierrez ◽  
Reyes Arranz ◽  
Angel Leon ◽  
...  
Keyword(s):  
Stem Cell ◽  
Stem Cell Transplantation ◽  
Cell Transplantation ◽  
Autologous Stem Cell Transplantation ◽  
Salvage Therapy ◽  
Front Line ◽  
Free Survival ◽  
Line Therapy ◽  
Gallium Scan

Abstract Background: Nodal aggressive PTCL have a poor prognosis with conventional chemotherapy regimens for aggressive non-Hodgkin lymphomas. Therefore innovative approaches are needed. Among them, strategies including consolidation with high-dose chemotherapy and autologous stem cell transplantation in front line therapy may improve the outcome of these diseases. Aim: To report the experience of a national cooperative group in 26 patients with aggressive nodal PTCL who underwent treatment including ASCT as consolidation of front line therapy. Patients and Methods: Twenty-six patients Gallium scan positive with nodal PTCL entered into the study: 11 cases of PTCL-unspecified (42%), 8 ALCL (31%) and 7 AIL (27%). Patients received three courses of MegaCHOP and subsequently were evaluated by CT scan and Gallium scan. Those patients Gallium scan negative received another course of MegaCHOP and then the transplant. Those patients Gallium scan positive after 3 courses of MegaCHOP received 2 courses of the IFE regimen (Ifosfamide 3.3g/m2 days 1–3 and Etoposide 300 mg/m2 days 1–3) and if at least achieved a partial response received the transplant otherwise they are out of the study. Median age was 44 years, 96% of the patients presented Ann Arbor stage III or IV; 54% presented B symptoms; 31% bone marrow involvement and 72% of the patients presented 2–3 factors of the a-IPI. Results: Thirteen patients (50%) achieved a CR after 3 courses of MegaCHOP and 12 patients received IFE as salvage therapy. Twenty patients out of the 26 initial patients were able to proceed to the transplant. After the transplant 85% of patients achieved a CR. The 6 patients who did not received the transplant was due to progression of the disease in 4 cases, lethal toxicity in one case and refusal in another case. With a median follow up of 35 months for alive patients, the overall survival (OS) and progression-free survival (PFS) at 3 years were 73% and 53%, respectively. OS, PFS and disease-free survival for the 20 patients who underwent the ASCT consolidation was 84%, 53% and 63%, respectively. Conclusion: Early salvage therapy for patients not in CR after 3 courses of chemotherapy and ASCT consolidation for chemosensitive patients may improve the outcome of patients with nodal aggressive PTCL. Larger series and longer follow up are needed to confirm this promising approach.

Allogeneic Stem Cell Transplantation in Angioimmunoblastic T-Cell Lymphoma (AITL): A Retrospective Survey from the Lymphoma Working Party (LWP) of the European Group for Blood and Marrow Transplantation (EBMT).

Blood ◽  
2007 ◽  
Vol 110 (11) ◽  
pp. 3042-3042
Author(s):  
Charalampia Kyriakou ◽  
C. Canals ◽  
G. Taghipour ◽  
J. Finke ◽  
H. Kolb ◽  
...  
Keyword(s):  
Overall Survival ◽  
Stem Cell ◽  
T Cell ◽  
Stem Cell Transplantation ◽  
Cell Transplantation ◽  
Relapse Rate ◽  
Allogeneic Stem Cell Transplantation ◽  
Cell Lymphoma ◽  
T Cell Lymphoma

Abstract AITL is a rare peripheral T-cell lymphoma characterised by an aggressive behaviour, which primarily affects the elderly. Chemotherapy regimens fail to alter the high relapse rate and overall survival hardly exceeds 25% at 5 years. To date, there is no information on the potential role of allogeneic stem cell transplantation (allo-SCT) in the management of AITL. We report the outcome of 39 patients with a median age of 47 years (24–68), who underwent an allo-SCT between 1995 and 2004 for AITL, and were reported to the EBMT registry. The median time from diagnosis to transplant was 10 months (4–72). Thirty-four patients (87%) had previously received two or more treatment lines, and 16 patients (41%) a previous autologous SCT. Fifteen patients (38%) had a primary refractory disease, 13 (33%) were transplanted in partial remission and the remaining patients were in complete remission (CR) (mostly in 2nd and 3rd CR). Twenty-four patients were transplanted from an HLA-identical sibling and 15 from a matched unrelated donor. A myeloablative conditioning regimen (MAC) was used in 21 patients (cyclophosphamide + total body irradiation in 14), while 18 patients received fludarabine-based reduced intensity conditionings (RIC). Peripheral blood was the source of stem cells in 35 patients (90%). Three patients failed to engraft (one patient in the RIC group). Twenty-one patients (54%) developed acute graft versus host disease (grade I-II, n=16; grade III-IV, n=5). Twenty-eight patients (72%) achieved a CR after the allogeneic procedure. Nine patients died from transplant related mortality (TRM) and 5 patients from disease progression. The cumulative incidence of TRM at 12 months was 19% for the MAC and 26% for the RIC group. After a median follow-up for the surviving patients of 20 months (6–74), 25 patients are alive. Relapse rates at 1 and 3 years were estimated at 10% and 18% for the MAC and 16 and 20% for the RIC patients. Progression free survival rates at 3 years were 67% and 50% and the overall survival at the same time 71% and 56% for the MAC and RIC group of patients, respectively. Although follow up is rather short, these data suggest that allo-SCT results in good overall response and is associated with a low relapse rate in this group of poor risk heavily pre-treated and rather elderly group of AITL patients. Allo-SCT could be considered a therapeutic option for eligible high-risk AITL patients. Nevertheless, the impact of this approach should be further explored in prospective collaborative studies.

Allogeneic Stem Cell Transplantation for Relapsed Follicular Non-Hodgkin’s Lymphoma: Single Centre Experience.

Blood ◽  
2007 ◽  
Vol 110 (11) ◽  
pp. 5054-5054
Author(s):  
Amir Peyman ◽  
Stephen Couban ◽  
Kara Thompson ◽  
Louis Fernandez ◽  
Donna L. Forrest ◽  
...  
Keyword(s):  
Stem Cell ◽  
Stem Cell Transplantation ◽  
Follicular Lymphoma ◽  
Cell Transplantation ◽  
Chronic Gvhd ◽  
Disease Free Survival ◽  
High Dose ◽  
Hematopoietic Stem ◽  
Free Survival ◽  
Grade 3

Abstract Between 1993 and 2005, 57 patients with follicular lymphoma underwent high-dose chemo/radiotherapy and allogeneic hematopoietic stem cell transplantation (HSCT), 49 Allogeneic, (16 Bone Marrow and 33 Peripheral Blood), 6 MIN, 2 MUD. Median age was 47 years. Median days to neutrophil and platelet engraftment after HSCT were 18 and 13 days respectively. Twenty-five patients experienced Acute GVHD and thirty-four had Chronic GVHD (12 mild and 22 extensive). Thirty-three patients were in grade 1, 17 in grade 2, 4 in grade 3 and 3 grade 4. As of their FLIPI score, 4, 14, 21 and 18 patients were calculated to have score of 0, 1, 2 and 3 respectively. Forty-one patients are alive. Two patients have relapsed, one a year and the other two years after HSCT. The 5 year survival was 71.9% (95% CI 57.5–82.2%) and 5 year survival was 67.2% (95% CI 52.3–78.5%). Transplant related mortality rate (TRM) in 5 year was 22.4% (95% CI 63.6–86.8%). No significant differences was found among FLIPI groups 0,1,2 and 3 in terms of overall, relapse-free survival, TRM Allogeneic HSCT for patients with progressive follicular lymphoma is feasible and may result in prolonged disease-free survival.

Early Mixed Chimerism After Allogeneic Stem Cell Transplantation with the Reduced-Toxicity IV Busulfan-Fludarabine (BuFlu) Regimen Does Not Independently Affect Long-Term Prognosis for Patients with AML/MDS.

Blood ◽  
2010 ◽  
Vol 116 (21) ◽  
pp. 3446-3446
Author(s):  
XiaoWen Tang ◽  
Marcos De Lima ◽  
Wei Wei ◽  
Alexandre Chiattone ◽  
Peter F. Thall ◽  
...  
Keyword(s):  
Stem Cell ◽  
Stem Cell Transplantation ◽  
Cell Transplantation ◽  
Allogeneic Stem Cell Transplantation ◽  
Disease Free Survival ◽  
Mixed Chimerism ◽  
Free Survival ◽  
Conditioning Therapy ◽  
Reduced Toxicity ◽  
Disease Free

Abstract Abstract 3446 Background: The achievement of a fully chimeric state, as opposed to mixed chimerism, has been associated with a more favorable outcome after allogeneic stem cell transplantation (allo-SCT) for leukemia. When using the reduced-toxicity IV Busulfan-Fludarabine (Bu-Flu) regimen (de Lima et al, BLOOD 2004;104:857-64) we were intrigued by a seemingly high incidence of early (day+30) mixed chimerism, yet a low incidence of serious toxicity, GvHD and high overall and disease-free survival, especially for patients transplanted in (any) remission (CR). We hypothesized that the introduction of highly sensitive PCR-based chimerism assessment technique, as well as separately assaying myeloid- and T-cell chimerism might provide more reliable data for assessing the prognostic value of chimerism in reference to overall (OS) and disease-free survival (DFS) after allo-SCT. Patients and methods: Chimerism assay was performed with PCR-based technique on informative loci, and multi-variate Cox models including chimerism and other covariates were fit for OS and DFS (See Table 1). Results: 206 AML/MDS patients were treated on two consecutive protocols with Flu at 40 mg/m2 daily for 4 days, each dose followed by IV Bu at 130 mg/m2 or pharmacokinetically targeted to an average systemic exposure of 6,000 mcMol-min. Recipients of an unrelated or one-Ag mismatched related graft received rabbit-ATG at a total dose of 4 mg/kg on days -3 to -1. GvHD prophylaxis was Tacrolimus with mini-dose MTX (5 mg/m2) on post-transplant days 1, 3, 6, and 11. There were 98 females and 108 males at a median age of 47 years (range 16–66). Sixty-six patients were in CR1, 48 in CR2, 18 had 1st chemotherapy-refractory relapse, 20 were in 1st or 2nd untreated relapse, 37 had primary induction failure, while 17 had high-risk MDS. One patient died before day 30, without chimerism studies, and 11 recovered with refractory leukemia. Median follow-up of patients still alive is 5.5 yrs (range 1.3–8.6). 193 patients who engrafted and were in CR on day +30 had chimerism analysis performed, 64% were full donor chimeras, and 36% had mixed chimerism (≥1% remaining host cell-derived DNA). As expected, being in CR prior to SCT and, if transplanted with active disease, to engraft and remain in CR or to achieve CR, respectively, were important predictors for survival. A cytogenetic “bad” prognostic subgroup (e.g. -5/-7), was of adverse importance. However, in the multivariate model neither higher age, up to age 65, or attainment of full vs. mixed donor chimerism by day +30 were of additional predictive value for either OS or DFS. (See Table 1). Conclusion: When the reduced-toxicity IV Bu-Flu regimen is used as conditioning therapy for AML/MDS only cytogenetic subgroup (Bad/others) and disease state (CR/No CR) at the start of conditioning therapy influenced DFS and OS. Neither patient age nor attaining complete chimerism on BMT day +30 were independently predictive of an altered prognosis in reference to OS and DFS. Disclosures: No relevant conflicts of interest to declare.

IL10-592 CC Genotype In the Donor Is Associated with a Significant Decrease of Relapse Rate and a Significant Increase of Event-Free Survival and Overall Survival After Allogeneic Hematopoietic Stem Cell Transplantation In Children with Hematological Malignancies

Blood ◽  
2011 ◽  
Vol 118 (21) ◽  
pp. 4459-4459
Author(s):  
Bernd Gruhn ◽  
Janine Voigt ◽  
Nadine Pfaffendorf-Regler ◽  
Ilona Wolff ◽  
Felix Zintl ◽  
...  
Keyword(s):  
Overall Survival ◽  
Stem Cell ◽  
Stem Cell Transplantation ◽  
Cell Transplantation ◽  
Relapse Rate ◽  
Myeloid Leukemia ◽  
Event Free Survival ◽  
Hematopoietic Stem ◽  
Free Survival ◽  
Il10 Gene

Abstract Abstract 4459 IL10 is a pivotal immunomodulatory cytokine and is usually regarded as a suppressor of the immune responses. However, IL10 has been shown to have some immunostimulatory effects. The IL10-592 CC genotype is associated wit higher production of IL10. Because IL10 may promote the development of alloimmunity we hypothesized that the IL10-592 CC genotype in the donor reduces the risk of relapse after hematopoietic stem cell transplantation (HSCT). A cohort of 211 children (median age, 12 years) with acute lymphoblastic leukemia (n=100), acute myeloid leukemia (n=62), myelodysplastic syndrome (n=30) or chronic myeloid leukemia (n=19) who underwent allogeneic bone marrow (n=153) or peripheral blood stem cell transplantation (n=58; T-cell depleted: n=26) in a single center and/or their respective donors was genotyped of IL10 gene for rs1800872 using TaqMan real-time polymerase chain reaction. The donor was HLA-matched unrelated in 48% of transplants and HLA-identical related in 42% of transplants. Conditioning regimen was myeloablative in all cases. Two forms of post-transplant immunosuppression predominated, cyclosporine A and methotrexate in 69% of transplants and cyclosporine A alone in 17% of transplants. Cell samples from the donor were available in 174 cases and from the patient in 197 cases. The IL10-592 CC genotype was present in 82 of the 174 donors (47.1%) and in 104 of the 197 patients (52.8%). Interestingly, we found a significantly reduced incidence of relapse in patients who were transplanted from a donor with the IL10-592 CC genotype (15.9% versus 30.4%; p=0.016). In addition, we observed a significant increase of event-free survival (52.4% versus 33.7%; p=0.019) and a significant increase of overall survival (54.9% versus 37.0%; p=0.040) if the IL10-592 CC genotype was present in the donor. The occurrence of the IL10-592 CC genotype, in either donors or recipients, had no significant impact on treatment related mortality, acute and chronic graft-versus host disease. In conclusion, IL10-592 CC genotype in the donor is associated with a significant decrease of relapse rate and a significant increase of event-free survival and overall survival after HSCT in children with hematological malignancies. This is the first study to describe an association of IL10 gene polymorphism with relapse rate after HSCT. Selecting a donor with the IL10-592 CC genotype could be a useful therapeutic strategy for improving the final outcome after allogeneic HSCT. Disclosures: No relevant conflicts of interest to declare.

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