Human Chorionic Gonadotropin Hormone Induces Indoleamine 2,3-Dioxygenase and Interleukin-10 Expression In Patients With Graft-Versus-Host-Disease

Blood ◽  
2013 ◽  
Vol 122 (21) ◽  
pp. 911-911
Author(s):  
Ahmet H. Elmaagacli ◽  
Markus Ditschkowski ◽  
Nina-Kristin Steckel ◽  
Hellmut Ottinger ◽  
Uwe Hillen ◽  
...  
Keyword(s):  
Low Dose ◽  
Chronic Gvhd ◽  
Interleukin 10 ◽  
Off Label Use ◽  
Graft Versus Host ◽  
Off Label ◽  
Human Chorionic Gonadotropin Hormone ◽  
Hcg Therapy ◽  
Severe Grade ◽  
Label Use

Abstract Background Chronic graft-versus-host disease (GVHD) is a major complication following allogeneic hematopoietic stem cell transplantation and is associated with a substantial morbidity and mortality. It is a systemic inflammatory disorder that reflects the lack of immune tolerance between donor-derived immune competent cells and host organs. Human chorionic gonadotropin hormone (hCG) is a natural occurring hormone during pregnancy secreted by syncytiotrophoblasts of the placenta. We had previously observed (Koldehoff et al; J Leukoc Biol 2011) that the rejection of transplanted skin was significantly delayed by hCG in a mouse skin transplant model and had also demonstrated that tryptophan-catabolizing enzyme, indoleamine-2,3-dioxygenase(IDO), interleukin-10 (IL 10) and T-regulatory cells (Tregs) increased significantly in females treated with hCG as preconditioning therapy for in-vitro-fertilization. Since all these factors are known to induce tolerance and given the low rate of adverse effects, we off-label used low dose of hCG to treat 20 patients as forth- or fifth-line therapy with steroid-refractory or intolerant severe-grade chronic GVHD. Patients Because all of these factors are known to induce tolerance and given the low rate of adverse effects in preconditioning therapy, we off-label used low dose of hCG (187 IU) to treat 8 male and 12 female patients (median age 48, r. 28-68) with moderate or severe grade of chronic GVHD according to the NIH criteria; all patients had been informed of the experimental state of this treatment and provided written consent. Results The median number of sites of chronic GVHD involvement per patient was 3 (range, 1-6). hCG therapy was started as 4 or 5th line-therapy together with preexisting medication with prednisone and a calcineurin inhibitor. Twelve of 20 patients (60%) had an objective partial response during 8 weeks of hCG treatment with at least 50% improvement according to the TSS score. Responses included softened skin and subcutaneous tissue; decreased erythema and extent of sclerodermatous, hidebound skin; improved joint mobility and gait; gastrointestinal improvements; and resolution of neuropathy. Nine patients had stable disease (6 with minor responses). Only one patient with previous ATG treatment showed progression of her liver GVHD (histologically proven) and died from GHVD. All other patients were well and alive. Daily low-dose hCG was well tolerated. Adverse events that were possibly related to hCG included reversible and asymptomatic CTCAE grade 4 hypertriglyceridemia (n=1), grade 2 constitutional symptoms (fever, malaise, fatigue; flush, breast enlargement). IDO expression increased up to 8 times and IL10-serum level up to 2 times after 3 weeks of hCG therapy (p<0.003 and p<0.04). T-regulatory cell expansion was documented in 3 patients. Conclusion This successful use of hCG in an immune disorder warrants further studies to assess its role as an immunosuppressant in GVHD and potentially other autoimmune disorders. Disclosures: Off Label Use: The off-label use of HCG will be presented here for the first tiem for treatment of chronic GVHD and will clearly marked as off-label use.

Pre-Transplant Rituximab Is Associated with Reduced Rate of Acute GvHD After RIC-Allosct In Lymphoma Patients: Results From A Retrospective Monocenter Analysis.

Blood ◽  
2010 ◽  
Vol 116 (21) ◽  
pp. 1319-1319
Author(s):  
Roberto Crocchiolo ◽  
Jean El Cheikh ◽  
Luca Castagna ◽  
Alix Helvig ◽  
Sabine Furst ◽  
...  
Keyword(s):  
Cumulative Dose ◽  
Acute Gvhd ◽  
Chronic Gvhd ◽  
Conditioning Regimen ◽  
Off Label Use ◽  
Off Label ◽  
Number Of Patients ◽  
Grade 3 ◽  
Reduced Rate ◽  
Label Use

Abstract Abstract 1319 Introduction: both B and T cells are implicated in the pathophysiology of graft-versus-host disease (GvHD) after allogeneic hematopoietic stem cell transplantation (AlloSCT). Anti-thymocyte globulin (ATG) administered during conditioning has been shown to reduce both acute and chronic GvHD, while rituximab has been claimed to reduce incidence of GvHD: previous studies indicated a reduced incidence of acute and/or chronic GvHD, but sometimes with controversial results. Here we present results from a retrospective, monocenter analysis on a selected population of lymphoma patients undergoing reduced-intensity (RIC) AlloSCT, with or without ATG in the conditioning regimen. Methods: adult patients receiving RIC-AlloSCT from a HLA-identical sibling donor for relapsed CD20+ lymphoproliferative disease at our Institution were included in the analysis. Data on patients and donors, conditioning regimen, use of rituximab and cumulative dose during the six and three months before AlloSCT were collected. Rituximab was administered in association or not with chemotherapy, according to each patient's treatment strategy. Analysis was conducted separately on patients receiving ATG (ATG cohort) or not (non-ATG cohort). Correlation analysis between ATG, rituximab cumulative dose before AlloSCT and grade 2–4, grade 3–4 acute GvHD (aGvHD), or limited/extensive chronic GvHD (cGvHD) was performed. Results: a total of 57 patients transplanted between Avril 1999 and November 2009 were included in the study, 18 and 39 in the non-ATG and ATG group respectively. Of these 57 patients, 32 were treated with rituximab for a median (range) cumulative dose within 6 months before AlloSCT of 1500 (375-3375) mg/mq, ending at a median (range) of 43 (5-177) days prior to transplant. Details are shown in table 1. Median follow-up was 749 days (146-4051). No significant differences existed between patients receiving rituximab vs. those without rituximab, with the exception of a different number of patients with CLL or FCL. Among the 18 non-ATG patients, we observed a slightly reduced rate of severe (grade 3 or 4) aGvHD in those patients who received >= 375 mg/mq rituximab within three months before AlloSCT (n=13) compared to those receiving < 375 mg/mq or no rituximab (n=5): 2/13 vs. 2/5 (p=ns). In the ATG cohort, rituximab use at a dose >= 375 mg/mq (n=10) within three months was associated with a reduced rate of severe aGvHD compared with < 375 mg/mq or no rituximab (n=29): 0/10 vs. 7/29 (p=0.08). Reduction of grade 2–4 aGvHD rate was also observed: 1/10 vs. 14/29 (p=0.03). No effect on cGvHD appeared in the two cohorts. Discussion: present data suggest a role of rituximab administered before AlloSCT in reducing the incidence of aGvHD. This effect was more pronounced when concomitant administration of ATG was performed during conditioning regimen, indicating a possibly sinergistic effect of both T- and B-cell depletion in preventing GvHD. Although retrospective and small-sized, the present analysis, conducted on a quite homogeneous population of patients, confirms previous findings and enhances further investigations on larger number of patients. Disclosures: Off Label Use: Zevalin is off-label use in conditioning regimen in France.

ATG Dose Correlates with Acute and Chronic GvHD In Patients Undergoing Reduced-Intensity Conditioning (RIC) Allogeneic Stem Cell Transplantation: A Large Retrospective Monocenter Analysis on 301 Patients.

Blood ◽  
2010 ◽  
Vol 116 (21) ◽  
pp. 3485-3485
Author(s):  
Roberto Crocchiolo ◽  
Sabine Furst ◽  
Luca Castagna ◽  
Jean El Cheikh ◽  
Catherine Faucher ◽  
...  
Keyword(s):  
Multivariate Analysis ◽  
Stem Cell ◽  
Stem Cell Transplantation ◽  
Cell Transplantation ◽  
Chronic Gvhd ◽  
Adult Patients ◽  
Off Label Use ◽  
Off Label ◽  
Grade 3 ◽  
Label Use

Abstract Abstract 3485 Introduction: RIC associating Fludarabine-Busulfan-ATG (FBA) is quite popular as preparative for allogeneic hematopoietic stem cell transplantation (RIC-AlloSCT). However the best association us still a matter of debate. Busulfan is crucial for disease control but limited by a dose-dependent toxicity and ATG plays a pivotal role in the prevention of both acute and chronic GvHD but with a potential higher relapse rate. Here we retrospectively compared different FBA regimens among adult patients transplanted at our Institution for a hematological malignancy, with the aim of identifying whether some pre- or peri-transplant variables are predictive of outcome. Patients and methods: on 635 patients allografted between May 1998 and Feb 2010, a total of 301 patients affected by malignancy received FBA-based RIC-AlloSCT and were the object of the present analysis. Comparisons between baseline patient, donor and AlloSCT characteristics with transplant outcome were performed: univariate and multivariate Cox regression analysis were used to find any correlation between the above mentioned variables and OS, DFS, NRM, relapse incidence, acute (aGvHD) and chronic (cGvHD) GvHD. Variables with p<0.20 were included in multivariate analysis, and only variables with a p<0.05 were retained in the final model. Results: median (range) follow-up was 917 (71-4051) days. Two-year OS, DFS and NRM were 66%, 58% and 20% for the entire cohort. Relapse at two years was 26%. Cumulative incidence of grade 2–4, grade 3–4, overall and extensive cGvHD were: 29%, 12%, 58% and 40%. In multivariate analysis, patient's age was significantly associated with OS, NRM, grade 2–4 and 3–4 aGvHD; disease status at transplant significantly correlated with DFS and relapse incidence. ATG at a dose of 5 mg/kg compared to 2.5 mg/kg, was significantly associated with a reduced risk of developing grade 3–4 aGvHD (HR= 0.46, 95% CI: 0.22–0.99, p=0.05) and cGvHD (HR= 0.33, 95% CI: 0.20–0.54, p<0.0001), without affecting relapse (p=n.s.). Overtime we modified our standard RIC from F5B2A1 (Fludarabine over 5 d, oral Bu over 2 d and ATG for1d) (N=114) to F5BX2A2 (Fludarabine over 5 d, IV Bu over 2 d and ATG over 2 d) (N=84). Population was not similar and notably older (51 vs. 57 years, p<0.0001) in the latter group. Despite this we observed similar NRM (22% vs. 23%: p=n.s.) in patients older than 55 years; in patients younger than 55 F5BX2A2 was associated with better but not statistically significant OS (77% vs. 65% at two years, p=0.21) and reduced NRM (9% vs. 18% at two years, p=0.10). Conclusions: in this large monocenter series of adult patients undergoing FBA-based RIC-AlloSCT, the use of ATG at a dose of 5 mg/kg appeared to significantly reduce incidence and severity of cGvHD and grade 3–4 aGvHD compared to ATG 2.5 mg/kg without increasing disease relapse. Moreover, despite patients' disparity between the two cohorts, reduced NRM was observed in patients < 55 years old treated with F5BX2A2 regimen with respect to those receiving F5B2A1. Disclosures: Off Label Use: Zevalin is off-label use in conditioning regimen in France.

Immunomodulation of Both Donors and Recipients with Atorvastatin As a Strategy for the Prevention of Acute Graft-Versus-Host Disease (aGVHD): Results of Two Parallel Prospective Trials in Recipients of Matched Sibling Allogeneic Hematopoietic Cell Transplantation (alloHCT)

Blood ◽  
2012 ◽  
Vol 120 (21) ◽  
pp. 1942-1942
Author(s):  
Mehdi Hamadani ◽  
Michael Craig ◽  
Scot Remick ◽  
Laura Gibson ◽  
William Petros ◽  
...  
Keyword(s):  
T Cell ◽  
Research Funding ◽  
Fungal Infections ◽  
Chronic Gvhd ◽  
Off Label Use ◽  
Phase Ii Trials ◽  
Off Label ◽  
Gvhd Prophylaxis ◽  
Matched Sibling ◽  
Label Use

Abstract Abstract 1942 Introduction: Acute GVHD is a leading cause of morbidity and mortality following alloHCT. Atorvastatin (a statin drug) is a potent immunomodulatory agent capable of suppressing T cell–dependent immune responses that holds promise as a novel and safe agent for the prophylaxis of aGVHD. In murine models atorvastatin administration to both donor and recipient mice (compared to prophylaxis in either donors or recipients alone), prevented aGVHD by inhibiting donor T-cell proliferation, inducing T-helper 2 polarization, and by inhibiting recipient antigen presenting cell function (Zeiser et al. Blood, 2007). Several retrospective studies also suggest statins as potential prophylactic agents for aGVHD. Methods: We report here the results of two parallel, ongoing, prospective, phase II trials (NCT01175148 & NCT01491958) evaluating the safety and efficacy of a ‘two-pronged’ strategy of atorvastatin administration as aGVHD prophylaxis, to both adult (age ≥18yrs) donors and recipients of matched sibling alloHCT. The approach was identical in both protocols. Subjects with a history of atorvastatin allergy/intolerance were not eligible. As GVHD prophylaxis, atorvastatin at 40mg/day orally was administered to sibling donors, starting 14–28 days before the anticipated 1st day of stem cell collection. In alloHCT recipients GVHD prophylaxis consisted of atorvastatin (40mg/day) administered from day -14 to day +180 (or until stopping immunosuppression, toxicity, development of grade [Gr] II-IV aGVHD, or severe chronic GVHD [cGVHD]). In addition all recipients received standard GVHD prophylaxis with tacrolimus and methotrexate. Ex vivo CD34+ cell selection or in vivo T-cell depletion was not permitted. Primary outcomes were rate of Gr II-IV aGVHD at day +100 and safety of atorvastatin administration to alloHCT donor/recipient pairs. Both trials tested the null hypothesis H0: p≥35%, vs. the alternate H1: p≤15%, where p is probability of Gr II-IV aGVHD at day 100. Secondary outcomes included rates of late-onset aGVHD, cGVHD, relapse, progression-free survival (PFS), and overall survival (OS). Results: Between September 2010 and June 2012, 34 donor/recipient pairs were enrolled at WVU (n=24) and OSU (n=10). Median donor age was 50.5 yrs (range 24–69). Median duration of atorvastatin prophylaxis in donors was 15 days (range 7–26). No atorvastatin related Gr 3–4 toxicities were seen in the healthy donors. Table 1 shows baseline patient (pt) characteristics. At transplantation 16 pts (47%) had high-risk disease, 12 (35%) were chemorefractory, 11 (32%) had HCT-CI of ≥3, 14 (41%) were female to male allografts, and 12 (35%) pts had ABO mismatched transplants. Median follow up of survivors is 158 days (range 31 – 658). Atorvastatin was well tolerated with no Gr 2–4 adverse events. All pts engrafted. The median time to ANC ≥500/μL was 18 days (range 5–25) and to platelets ≥20k/μL was 15 days (range 11–51). The median day 100 chimerism was 85.5% (55–100%) for T-cells and 100% (26–100%) for myeloid cells. Respective numbers at day 180 are 99.5% and 100%. Among 34 evaluable pts, the cumulative incidences (CI) of Gr II-IV and Gr III–IV aGVHD at day 100 were 6.0 ± 4.2% and 0% respectively. Respective CI rates at day 180 are 16.7 ± 8.3% and 10.2 ± 7%. CI of mild/moderate and severe cGVHD at 1 year are 15.8 ± 8.9% and 18.3 ± 10.2%, respectively. Infectious complications were infrequent, with no fungal infections or EBV reactivations and few CMV reactivations (n=3). Non-relapse mortality was 0% at day 100 and 4.5% at day 180. CI of relapse at day 180 was 27.6 ± 9.2%. One year PFS and OS estimates are 54% and 66%, respectively. Conclusions: A two-pronged immunomodulatory strategy of atorvastatin administration to alloHCT donors/recipients appears to be a feasible, safe and potentially effective modality for aGVHD prophylaxis. Final results of NCT01175148 & updated results of NCT01491958 will be presented at the meeting. Disclosures: Hamadani: Celgene Corp: Speakers Bureau; American Cancer Society 116837-IRG-09-061-01: Research Funding; ASBMT & Millennium New Investigator Award: Research Funding; Conquer Cancer Foundation of ASCO: Research Funding. Off Label Use: Off Label use of atorvastatin for GVHD prophylaxis. Efebera:(NIA) K12 CA1333250: Research Funding; Leukemia and Lymphoma Society: Research Funding.

Low Dose Azacitidine (AZA) Reduces the Incidence of Chronic Graft-Versus-Host Disease (cGVHD) After Allogeneic Hematopoietic Stem Cell Transplantation (HSCT)

Blood ◽  
2012 ◽  
Vol 120 (21) ◽  
pp. 742-742 ◽  
Author(s):  
Marcos de Lima ◽  
Simrit Parmar ◽  
Julianne J Chen ◽  
Sergio A Giralt ◽  
Gabriela Rondon ◽  
...  
Keyword(s):  
Stem Cell ◽  
Cumulative Incidence ◽  
Research Funding ◽  
Low Dose ◽  
Control Group ◽  
Cell Transplant ◽  
Off Label Use ◽  
Landmark Analysis ◽  
Off Label ◽  
Label Use

Abstract Abstract 742 AZA has immunomodulatory properties that may affect donor lymphocytes favorably, potentially leading to less GVHD after HSCT. We have been investigating low-dose AZA (32 mg/m2 daily for 5 days) to prevent AML/MDS relapse after HSCT. Interestingly, in our dose finding phase I study (Cancer, 2010) there was a suggestion of less cGVHD with longer AZA treatments. We then hypothesized that this approach leads to less cGVHD, and performed a comparison of patients that received AZA to prevent relapse versus historic controls that did not receive the drug. Major objective of this analysis is to determine the cumulative incidence of cGVHD with versus without AZA. Methods. Patients received AZA based on high risk of relapse disease, starting at a median of 45 days from transplant (range, 17–149). AZA effect on aGVHD was not studied since the drug was started after most cases of aGVHD had already occurred or/and had resolved or improved. Patients with active acute GVHD (aGVHD) were not eligible to receive AZA. Median dose was 32 mg/m2 (range, 8–40). Median number of AZA cycles was 3 (range, 1–54), and median time on AZA for patients that received >3 cycles (n=37) was 144 days (range, 93–1329). Using a computer algorithm, we randomly selected from our departmental database a control group consisting of patients who had received HSCT within the same time period, and had similar GVHD prophylaxis, stem cell source, and comparable low risk of grade II-IV aGVHD (Table). Two hundred and thirty patients were identified fulfilling these criteria. The rate of cGVHD was compared between the AZA group (grouped as 1–3 cycles and >3 cycles) and the control group, in a landmark analysis starting at 6 months after HSCT. Leukemia relapse or death in remission before cGVHD onset were considered as competing risks in this analysis. Results. Median follow-up was 25 months (range, 1–99) in the AZA group, and 31 months (range, 1.5–117) in the control group. 29, 24, and 115 patients in the >3 AZA cycles, 1–3 AZA cycles, and the control group were evaluable for the 6-month landmark analysis, respectively. The numbers of patients developing cGVHD and the HR at 2 years in this analysis were as follows: 53 of 115 controls (reference group), 11 of 24 patients who received 1–3 AZA cycles (HR at 2 years, 0.9; P=NS), and 6 of 29 patients who received >3 AZA cycles (HR at 2 years, 0.4; 95% confidence interval (CI), 0.1–0.8; P=0.02) developed cGVHD. Similarly, in a landmark analysis, the cumulative incidence of cGVHD was significantly lower in the subgroup that received >3 AZA cycles (figure). Conclusion. Low-dose AZA appears to reduce the likelihood of developing cGVHD. We are investigating if this effect is associated with preservation or improvement of the graft-versus-leukemia effect in an ongoing, randomized study. Disclosures: de Lima: Celgene: Research Funding. Off Label Use: azacitidine: off-label use as maintenance therapy following allogeneic stem cell transplant for MDS/AML. garcia Manero:celgene: Research Funding.

scholarly journals Low dose Rituximab for Preemptive Management of Thrombotic Thrombocytopenic Purpura ( TTP )

Blood ◽  
2014 ◽  
Vol 124 (21) ◽  
pp. 5029-5029
Author(s):  
John C. Nelson
Keyword(s):  
Low Dose ◽  
Normal Values ◽  
Off Label Use ◽  
Off Label ◽  
Adamts13 Deficiency ◽  
Igg Deficiency ◽  
Autoimmune Cytopenias ◽  
Reported Data ◽  
Clinical Changes ◽  
Label Use

Abstract Low dose rituximab has been successful in treating some patients with autoimmune cytopenias. Recently reported data indicate preemptive rituximab may postpone hematologic relapses of TTP in patients with chronic severe ADAMTS13 deficiency. A now 22-year-old woman had multi-relapsing TTP with five episodes over the previous 10 years, three of which were successfully treated with four doses of rituximab 375 mg/m2. The most recent course in 2009 was given preemptively because intense ADAMTS13 monitoring had shown that previous hematologic relapses followed shortly after developing severe ADAMTS13 deficiency. Asymptomatic chronic IgG deficiency less than 300 mg% had followed this most recent rituximab course given in 2009. In 2014, continued intense ADAMTS13 monitering disclosed a new progressive decrease in ADAMTS13 levels from normal to severely deficient levels with a weak inhibitor, but no hematologic or clinical changes. Just two 100 mg rituximab doses have been followed by a progressive rise of ADAMTS13 levels to solidly normal values with significant improvement by day 13 post initiation and normalization by day 34. Low dose rituximab could be a viable alternative for preemptively managing TTP patients with persistently severly low ADAMTS13 levels. Disclosures Off Label Use: Off label use of rituximab to treat TTP.

scholarly journals Off-Label Use of Ruxolitinib In Refractory Graft-Versus-Host Disease After Allogenic Stem Cell Transplantation

2016 ◽  
Vol 19 (7) ◽  
pp. A576 ◽  
Author(s):  
LL Poyatos-Ruiz ◽  
MD Vega-Coca ◽  
S Flores-Moreno ◽  
A Garcia-Avello ◽  
L Abdel-kader-Martin ◽  
...  
Keyword(s):  
Stem Cell ◽  
Stem Cell Transplantation ◽  
Cell Transplantation ◽  
Graft Versus Host Disease ◽  
Off Label Use ◽  
Allogenic Stem Cell Transplantation ◽  
Host Disease ◽  
Graft Versus Host ◽  
Off Label ◽  
Label Use

Allogeneic Hematopoietic Cell Transplantation in AML: Comparable Results After Matched or Mismatched Unrelated Versus Matched Related Transplantation.

Blood ◽  
2009 ◽  
Vol 114 (22) ◽  
pp. 1199-1199 ◽  
Author(s):  
Birgit Federmann ◽  
Christoph Faul ◽  
Wichard Vogel ◽  
Lothar Kanz ◽  
Wolfgang Andreas Bethge
Keyword(s):  
Overall Survival ◽  
Cell Transplantation ◽  
Hematopoietic Cell Transplantation ◽  
Chronic Gvhd ◽  
Unrelated Donor ◽  
Off Label Use ◽  
Hematopoietic Stem ◽  
Off Label ◽  
Significant Difference ◽  
Label Use

Abstract Abstract 1199 Poster Board I-221 Currently, most treatment algorithms reserve the use of allogeneic hematopoietic stem cell transplantation (HCT) in patients with acute myeloid leukemia (AML) in first complete remission (CR) to patients with a matched related donor (MRD) and intermediate/high-risk disease. However, the role of HCT from a matched or mismatched unrelated donor (MUD/MMUD) in patients with AML remains to be defined. We retrospectively analyzed a cohort of 219 consecutive adult patients (98 female, 121 male) with AML who received HCT from 2000-2009 at our institution. The patients were transplanted after either myeloablative (MAC, n=139) or dose-reduced-conditioning regimens (RIC, n=80). Median age of patients was 50 years (range, 18-76). 77 patients were transplanted from MRD, 80 patients from MUD and 62 patients from MMUD (one antigen mismatch (MM)=31; two antigen MM=2; one allel MM=24; two allel MM=3, one antigen/one allel MM= 2). In all but six patients receiving MMUD grafts, ATG was included in the conditioning. Age, risk profile and pretreatment were evenly distributed among the three cohorts of patients. At time of HCT 22 (MRD), 18 (MUD) and 28 (MMUD) patients were not in CR. Current overall survival is 40 of 77 (52%) in patients transplanted from MRD, 48 of 80 (60%) from MUD and 34 of 62 (55%) from MMUD with a median follow-up of 1309 (range, 98-3173), 796 (range, 87-3075) and 648 (range, 111-1973) days of alive patients, respectively. Kaplan-Meier-estimated 3-year overall survival (OS) was similar with 54% after MRD-, 56% after MUD- and 46% after MMUD-HCT (p=0.4554). In patients transplanted in CR, 3-year estimated OS was also comparable (64% MRD vs. 58% MUD vs. 55% MMUD, p=0.6614). However, in patients transplanted in partial remission (PR) we observed a trend for a better survival in patients receiving a MUD graft (30% MRD vs. 46% MUD vs. 39% MMUD, p=0.1707). In the patients receiving MAC we observed a better OS compared to RIC with an estimated 3-year OS of 58% vs. 38% (p=0.1047) mainly due to a lower incidence of relapse. In the subgroup of patients receiving MRD-HCT this survival benefit was significant (61% vs. 21%, p= 0.0327) while there was only a trend for MUD- or MMUD-HCT (60% vs 45%, p=0.5702 and 49% vs. 43%, p= 0.7566, respectively). There was no significant difference in the incidence of acute GvHD >II with 25% (MRD), 35% (MUD) and 34% (MMUD) or chronic GvHD with 43% (MRD), 46% (MUD) and 34% (MMUD), respectively. A significant better survival of patients with limited cGvHD vs. extensive or without cGvHD (estimated 3-year OS 73% vs. 34% vs. 47%, p=0.0001) was observed. This advantage was present in all subgroups with a significant better survival in the group with MRD (86% vs. 38% p= 0.0034), a trend in MUD (67% vs. 55% p= 0.0564) and MMUD (59% vs. 55%, p= 0.3111). No significant influence on survival or GVHD of the degree and loci of HLA-mismatch could be detected. In conclusion in our cohort of patients, HCT from MUD or MMUD in AML resulted in a similar outcome compared to MRD. In patients with PR at time of HCT, the use of MUD and occurrence of limited cGVHD may lead to improved survival due to an enhanced graft-versus-leukemia-effect. Disclosures: Off Label Use: some chemotherapeutical agents in the conditioning are off-label-use.

Efficacy and Safety of Peg-Interferon-α2a In Myelofibrosis: a Study of the FIM and GEM French Cooperative Groups

Blood ◽  
2010 ◽  
Vol 116 (21) ◽  
pp. 4103-4103 ◽  
Author(s):  
Jean-Christophe Ianotto ◽  
Françoise Boyer-Perrard ◽  
Jean-Loup Demory ◽  
Jerome Rey ◽  
Lydia Roy ◽  
...  
Keyword(s):  
Observational Study ◽  
Low Dose ◽  
Therapeutic Option ◽  
Complete Response ◽  
Dose Schedule ◽  
Off Label Use ◽  
Off Label ◽  
Small Series ◽  
Interferon Α2a ◽  
Label Use

Abstract Abstract 4103 Background: The moderate effect of most palliative treatments in primary and secondary myelofibrosis (MF), in addition to the limited possibilities of allogeneic stem cell transplantation, has incited physicians to look for alternative treatments. Since 1987, several studies have suggested that interferon may be beneficial in the treatment of MF. However, important hematological and general limiting toxicities frequently occur in MF patients (pts), leading to rapid treatment discontinuation in more than 50% of pts. Better results were recently reported in a small series of 13 MF pts treated with Peg-Interferon-α2a (Ianotto et al., Br J Haematol, 2009). The present study aimed to collect data of pts with primary and secondary MF treated with Peg-Interferon-α2a in French centers members of the FIM (French Intergroup of Myeloproliferative disorders) and GEM (Groupe d'Etudes des Myelofibroses) groups, to better assess tolerance and efficacy of this form of interferon in MF. Patients and Methods: Between Dec 2006 and Feb 2010, 39 MF pts treated with Peg-Interferon-α2a were registered from 10 different French centers affiliated to FIM and GEM groups. Age of pts ranged from 41 to 81 years, 21 were men and 18 women. Sixteen pts had primary MF, 13 had post-PV and 10 post-ET MF, respectively. Twenty-five patients (64%) were JAK2V617F positive. Twenty-eight patients had previously received other cytoreductive treatment. Clinical and biological parameters were collected at diagnosis and every 3 months. Responses were assessed according to the International Working Group for Myelofibrosis Research and Treatment (IWG-MRT) criteria. Analyses were performed in July 2010, after a median follow-up of 18 months (range: 3 – 42 months). Results: Among the 28 patients with splenomegaly, we observed 10 responses (36%) including 7 complete and 3 partial responses. Fourteen patients had constitutional symptoms which resolved in 8 of them (57%). Seven of 15 patients (47%) with an initial hemoglobin level below 100 g/L achieved complete response (CR). Three of 8 (37%) transfused pts became transfusion-independent. Twenty-two patients had abnormal WBC count which normalized in 13 of them (59%). Platelet count was abnormal in 27 patients, and 14 (52%) achieved CR with Peg-Interferon-α2a treatment. The evolution of the JAK2V617F allele burden is currently under investigation and will be presented at the meeting. The initial median dose of Peg-Interferon-α2a effectively received was 103 μ g/wk, further decreased to a median of 85 μ g/wk after one year. At time of analysis, treatment was stopped in 11/39 (28%) pts due to side effects, inefficacy or hematologic evolution. Conclusion: In this observational study, we found higher efficacy and better tolerance of interferon than previously reported in patients with primary or secondary MF. Such results were possibly due to a better tolerance of the pegylated form used, and to the low-dose schedule applied by the physicians. Our results suggest at least that Peg-Interferon-α2a should be considered as a possible therapeutic option in selected MF patients. Future clinical trials in MF will hopefully involve combinations of low dose Peg-Interferon-α2a with JAK2-inhibitors or immunomodulatory agents in order to improve tolerability and increase efficacy. Disclosures: Off Label Use: This is an observational study of the off-label use of peg-Interferon-alfa2a in myelofibrosis.

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