scholarly journals Reduced Intensity Conditioning and Dual T-Cell Modulation Improves Gvhd Free, Relapse Free Survival in AML Patients Compared with Myeloablative Conditioning

Blood ◽  
2019 ◽  
Vol 134 (Supplement_1) ◽  
pp. 4590-4590
Author(s):  
Maria Queralt Salas ◽  
Shiyi Chen ◽  
Wilson Lam ◽  
David Loach ◽  
Fotios V. Michelis ◽  
...  
Keyword(s):  
Quality Of Life ◽  
T Cell ◽  
Cumulative Incidence ◽  
Chronic Gvhd ◽  
Relapse Free Survival ◽  
Reduced Intensity Conditioning ◽  
Free Survival ◽  
Gvhd Prophylaxis ◽  
Reduced Intensity

BACKGROUND The efficacy of allogeneic hematopoietic stem cell transplantation (allo-HSCT) in acute myeloid leukemia (AML) relies on the antileukemic effect of the conditioning regimen and the graft-versus leukemia (GVL) effect mediated by donor T-cells. Leveraging the GVL effect while reducing toxicity enables reduced intensity conditioning (RIC) to be used to older or frail patients, but may lead to higher rates of graft-versus-host disease (GVHD), impairing later quality of life. Novel T-cell modulation strategies may limit the incidence of GVHD while preserving antileukemic activity leading to better outcomes. Herein, we compare the outcomes of AML patients treated with myeloablative (MAC) and RIC regimens including patients receiving dual T-cell depletion using Anti-Thymocyte Globulin (ATG) and Post-Transplant Cyclophosphamide (PTCy). METHODS Between 2013 and 2018, 362 adults with AML in complete remission underwent allo-HSCT and were included in the study. Overall, 112 (31%) patients received MAC and 250 (69%) received RIC regimens. MAC consisted of Flu(4), Bu (4mg) and 400cGy of total body irradiation (TBI). RIC regimen consisted on Flu (4), Bu (2) and 200cGy TBI in 249 recipients and one received clofarabine/busulfan. One hundred seventy-one (68.4%) the recipients who received RIC regimen, received a novel dual T-cell depletion strategy using ATG (total dose of 4.5mg/kg in 130 patients and 2mg/kg in 41 recipients), PTCy, and cyclosporine for GVHD prophylaxis. Peripheral blood stem cell (PBSC) grafts were used in 98.9% of the recipients. Data was collected retrospectively and updated on April 2019. The cumulative incidence of GVHD was assessed accounting relapse and death as competing events. A multivariate analysis for overall survival (OS), relapse-free survival (RFS) and GVHD-Free/RFS (GFRFS) was conducted controlled by those variables found to be significant in univariate analysis. RESULTS Baseline information is summarized in Table 1. The incidence of grade II-IV and III-IV acute GVHD at day +100, and moderate/severe chronic GVHD at 1 year was respectively: 28.6%, 10.5%, and 18.4%. RIC was associated with a significantly lower cumulative incidence of clinically relevant acute and chronic GVHD (P<0.05). Main outcome information is summarized in tables 1 and 2, and displayed graphically in figures A-F. With a median follow-up of 3.7 years, 68 (18.8%) recipients relapsed and 160 (44.2%) died. The 2-years OS, RFS, and GRFS were 53.8%, 50.8%, and 33.8%, respectively. OS, RFS, non-relapse mortality, and cumulative incidence of relapse were not significantly affected by regimen intensity (P>0.05). However, RIC regimens were associated with superior GRFS. Forty-three (12.7%) recipients had a high Disease Risk Index (DRI). Conditioning intensity was not a significant risk factor for OS (HR 0.9; P=0.931) or RFS (HR 1; P=0.902) in this group of patients. Tables 3 and 4 show the results from multivariate analysis for OS, RFS, and GFRFS. Older patients, those with high DRI, or recipients of 9/10 matched unrelated donor (MUD) grafts had significantly worse OS and RFS. GVHD prophylaxis with dual T-cell modulation (ATG-PTCy-CsA) was the only protective parameter for a better GRFS (HR 0.5; P=0.005). CONCLUSION In AML patients, RIC with PBSC allografts and dual T-cell modulation with ATG and PTCy led to superior GRFS when compared with MAC regimens. Reduction in the cumulative incidence of clinically significant acute and chronic GVHD may be possible without compromising on the efficacy of the GVL effect. The use of this GVHD prophylaxis strategy, along with mitigation of conditioning toxicity by using RIC, may result in better quality of life. Further investigations would be done with the use of this novel GVHD prophylaxis in the setting of MAC regiments. Dual T-cell suppression leads to increased infectious complications including viral reactivations. The use of lower doses of ATG, or individualized dosing strategies based on lymphocyte count may help to further optimize this strategy. Disclosures Michelis: CSL Behring: Other: Financial Support. Mattsson:Celgene: Honoraria; Therakos: Honoraria; Gilead: Honoraria.

Synergy of Unrelated Donor and Full Intensity Conditioning Breaks the Control of Graft Versus Host Disease By Alemtuzumab

Blood ◽  
2014 ◽  
Vol 124 (21) ◽  
pp. 1206-1206
Author(s):  
Olivia Laverick ◽  
Amy Publicover ◽  
Laura Jardine ◽  
Kile Green ◽  
Alan Potter ◽  
...  
Keyword(s):  
T Cell ◽  
Acute Gvhd ◽  
Chronic Gvhd ◽  
Cell Depletion ◽  
Reduced Intensity Conditioning ◽  
T Cell Depletion ◽  
Gvhd Prophylaxis ◽  
Full Intensity ◽  
Conditioning Intensity ◽  
Reduced Intensity

Abstract Many variables influence the risk of graft versus host disease following hematopoietic stem cell transplantation. Comparison between preparative regimens is hampered by the use of many different combinations of chemotherapy and radiotherapy, varying intensity of conditioning, use of T cell depletion and donors who are either siblings or unrelated volunteers. Many reduced intensity regimens also incorporate enhanced GVHD prophylaxis with in vivo T cell depletion. Here we describe a cohort of patients prepared in a modular fashion with either reduced or full intensity conditioning combined with a uniform GVHD prophylaxis regimen for all transplants with sibling donors (alemtuzumab 30mg) and for all with unrelated donors (UD; alemtuzumab 60mg). Thus it was possible to dissect independently the effect of conditioning intensity and sibling or UD type upon GVHD risk in this settig of in vivo T cell depletion. Patients and analysis: the study was a retrospective analysis of 258 sequential transplants performed in adults with hematological malignancy between September 2005 and September 2013 at a single UK institution. Reduced intensity conditioning (n = 221) included fludarabine 150mg/m2 plus melphalan 140mg/m2 or fludarabine 150mg/m2 plus busulfan 9.6mg/kg. Full intensity transplants (n = 37) received 12Gy TBI plus melphalan 140mg/m2, 12Gy TBI plus cyclophosphamide 120mg/kg, or busulfan 16mg/kg plus cyclophosphamide 120mg/kg. All patients with sibling donors received 30mg alemtuzumab and those with UD received a 60mg of alemtuzumab. UD matching was similar in both reduced intensity and full intensity cohorts (92.2% and 86.5% 10/10 matches, respectively) but patients receiving reduced intensity were older than those receiving full intensity conditioning (median age 51 vs 31; p < 0.001). Outcome was analyzed according to EBMT guidelines. Relapse, non-relapse mortality and cGVHD were treated as competing risks and analysed as cumulative incidence. Outcome: the incidence of acute GVHD grades I-IV was comparable between reduced intensity and full intensity sibling transplants (45% vs 45%; p = NS) indicating a lack of effect of conditioning intensity upon GVHD risk in this setting. There was a slight increase in the risk of GVHD between reduced intensity UD compared with reduced intensity sibling donor transplants (57% vs 45%; p = NS) but a marked synergistic increase between UD transplants performed with full intensity compared with reduced intensity conditioning (100% vs 57%; p = < 0.001). The incidence of grades III-IV acute GVHD was also higher in full intensity UD transplants (16%) compared with reduced intensity UD transplants (5%). The incidence of chronic GVHD was also highest in full intensity UD transplants but both conditioning intensity and UD contributed in an additive manner: the rate of chronic GVHD progressed from 33% to 44% in reduced intensity and full intensity sibling transplants respectively and from 57% to 75% for reduced and full intensity UD transplants, respectively. Two year overall survival was comparable in all groups, ranging from 55% to 70%. In keeping with the higher rates of acute GVHD in full intensity transplants performed with UD, this group experienced the lowest relapse risk (15% vs 29% for all the other groups combined; p = 0.04) but the highest non-relapse mortality, reaching 41% at 2 years compared with 28% for all the other groups combined (p = 0.08). Conclusion: these results show that alemtuzumab provides good protection from acute GVHD in reduced intensity transplantation from sibling and UD. In sibling transplants given identical GVHD prophylaxis, full intensity conditioning does not increase the risk of GVHD. In contrast, a slight increase in GVHD risk with UD transplants seen with reduced intensity conditioning, is amplified in a synergistic manner by full intensity conditioning. This is associated with a high non-relapse mortality, even though the median age of full intensity patients is more than 20 years younger than those receiving reduced intensity conditioning. Disclosures No relevant conflicts of interest to declare.

Tacrolimus and Sirolimus without Methotrexate as Acute GVHD Prophylaxis after Matched Related Donor Reduced Intensity Conditioning (RIC) Stem Cell Transplantation (SCT).

Blood ◽  
2007 ◽  
Vol 110 (11) ◽  
pp. 3046-3046 ◽  
Author(s):  
Vincent T. Ho ◽  
Haesook Kim ◽  
Shuli Li ◽  
Corey Cutler ◽  
John Koreth ◽  
...  
Keyword(s):  
Cumulative Incidence ◽  
Acute Gvhd ◽  
Chronic Gvhd ◽  
Reduced Intensity Conditioning ◽  
Historical Cohort ◽  
Post Transplant ◽  
Donor Chimerism ◽  
Gvhd Prophylaxis ◽  
Grade Ii ◽  
Reduced Intensity

Abstract We have previously shown that the combination of tacrolimus and sirolimus (TAC/SIR) without methotrexate (MTX) is a safe and effective regimen for GVHD prophylaxis after myeloablative SCT. However, TAC/SIR has not been investigated in the RIC setting. We hereby report a prospective phase II trial testing TAC/SIR as GVHD prophylaxis after RIC SCT from matched related donors (MRD). All patients received fludarabine (FLU) 30 mg/m2 IV and intravenous busulfan (BU) 0.8 mg/kg IV daily × 4 days (day -5 thru day -2) as conditioning, followed by transplantation of filgrastim mobilized peripheral blood stem cells. Filgrastim 5 mcg/kg SC QD was started on day +1 until neutrophil engraftment. Tacrolimus and sirolimus were started on day-3, and doses were adjusted to maintain target serum trough levels 5–10 ng/ml and 3–12 ng/ml, respectively. Twenty-six patients have been transplanted, with a median age of 52 years (range 29–64 yrs). Diagnoses include NHL (8), AML (6), HD (5), CLL/SLL (3), CML (2), MDS (1), MM (1). Median CD34+ cells infused was 8.06 × 106 cells/kg (range: 2.96–38.0 × 106 cells/kg). All patients had sustained hematologic engraftment. Only 4 (15%) patients developed neutropenia below ANC 500, and 6 (23%) had platelet counts below 20K. One patient had late graft failure at 7 months post transplant. Grade II-IV acute GVHD incidence was 20%, with grade III-IV incidence of 12%. No hepatic VOD or thrombotic microangiopathy was observed. Day +100 transplant related mortality (TRM) was 0%. The cumulative incidences of TRM and relapse at 1 year were 4% and 38%, respectively. The cumulative incidence of chronic GVHD at 1 year was 74%. A high level (>90%) of donor-derived hematopoiesis was achieved in 68% by 1 month post transplant. Median donor chimerism at between day 20–50 post transplant was 93.5% (range 32%-99%), and 94% (range 22%-100%) at day 85–115. With a median follow-up of 13.5 months among survivors (range 5.5–19 months), progression-free survival (PFS) and overall survival (OS) at 1 year were 58% and 79%, respectively. Compared to a historical cohort of 47 MRD transplant recipients treated with the same FLU/BU conditioning regimen and using TAC/SIR ± mini-MTX (5 mg/m2 IV day +1,3,6) as GVHD prophylaxis, there was no statistical difference between TAC/SIR vs. TAC/SIR/MTX in the incidence of grade II-IV acute GVHD (20% vs 11%, p= 0.48), cumulative incidence of relapse at year (38% vs. 57%, p= 0.25), 1-yr PFS (58% vs. 41%, p= 0.33), or 1-yr OS (79% vs. 73%, p= 0.79). These results demonstrate that omission of mini-MTX is permissible, and that the combination of TAC/SIR alone as GVHD prophylaxis following reduced intensity conditioning with FLU/BU is associated with low rates of acute GVHD, TRM, and high levels of donor chimerism after MRD SCT.

Comparison of Outcomes Between 2-Year Survivors After Myeloablative and Reduced-Intensity Conditioning Allogeneic Hematopoietic Stem Cell Transplantation.

Blood ◽  
2009 ◽  
Vol 114 (22) ◽  
pp. 3307-3307
Author(s):  
Ronald Sobecks ◽  
Robert Dean ◽  
Lisa Rybicki ◽  
Matt Kalaycio ◽  
Brad Pohlman ◽  
...  
Keyword(s):  
Chronic Gvhd ◽  
Multivariable Analysis ◽  
Secondary Malignancy ◽  
Disease Relapse ◽  
Cmv Infection ◽  
Relapse Free Survival ◽  
Reduced Intensity Conditioning ◽  
Hematopoietic Stem ◽  
Free Survival ◽  
Reduced Intensity

Abstract Abstract 3307 Poster Board III-195 Myeloablative (MA) and reduced-intensity conditioning (RIC) allogeneic hematopoietic stem cell transplantation (alloHSCT) are both effective treatment approaches for patients with otherwise incurable hematologic diseases. However, patients who survive beyond 2 years are still at risk for significant morbidity and mortality. Differences in these later post-transplant outcomes may exist between those patients who received MA and RIC regimens. We therefore investigated outcomes on 677 patients (590 MA and 87 RIC) with hematologic diseases who underwent alloHSCT at our institution from 1/90-12/06. 235 MA and 37 RIC patients survived >2 years (40% vs. 42%, respectively, p=0.63). Factors predictive for surviving >2 years on multivariable analysis included younger age, greater Karnofsky performance status (KPS) at transplant, related donor and HLA matched donor. For > 2 yrs survivors, as compared to those treated with MA conditioning the RIC patients were older (median age 55 vs. 39 yrs, p<0.001), had better KPS at transplant (p<0.001), more commonly had lymphoid diagnoses (24 [65%] vs. 62[28%], p<0.001), had longer median time from diagnosis to transplant (19 vs. 6 mos, p<0.001), had more prior chemotherapy (p<0.001) and radiation therapy (p=0.036), more often received a TBI-based preparative regimen (100% vs. 15%, p<0.001) and peripheral blood stem cells (100% vs. 5%, p<0.001). There were no differences between the groups regarding gender, race, comorbidity index score, donor relationship, donor to recipient gender, HLA matched transplants, incidence or severity of acute or chronic GVHD, CMV infection, other infections or overall survival. Disease relapse was higher in the RIC group (6[16%] vs. 22[9%], p=0.048). Currently, for these >2 yr survivors 178 (76%) MA and 28 (76%) RIC patients remain alive at median follow-ups of 72 (range, 3-196) vs. 33 mos (range, 5-86), respectively (p<0.001). Death occurred most commonly for the MA pts due to relapse, then chronic GVHD, pulmonary toxicity, infection and secondary malignancy, while relapse and secondary malignancy were the most common causes for RIC pts. As compared to those with lymphoid diseases those with myeloid diseases had superior relapse-free survival (RFS) (Figure, p=0.012) and tended to have better overall survival (OS) (p=0.09). Myeloid disease status was also predictive of lower disease relapse (p=0.005) and better relapse-free survival (p=0.014) on multivariable analysis. However, no differences in CMV infection, other infections, incidence and severity of chronic GVHD, relapse, RFS or OS were found when comparing MA vs. RIC patients for myeloid and lymphoid diseases independently. We conclude that the majority of MA and RIC patients surviving >2yrs after alloHSCT remain alive and relapse-free. The superior RFS for patients with myeloid diseases is likely related to a more robust graft-vs-malignancy effect. Further strategies with novel approaches to decrease late relapses for these patients are warranted. Disclosures No relevant conflicts of interest to declare.

Age up to 75 Years Does Not Influence the Outcomes of Allogeneic Hematopoietic Stem Cell Transplantation in Acute Myeloid Leukemia and Myelodysplastic Syndrome

Blood ◽  
2016 ◽  
Vol 128 (22) ◽  
pp. 3501-3501
Author(s):  
Dipenkumar Modi ◽  
Abhinav Deol ◽  
Seongho Kim ◽  
Kendra Mellert ◽  
Marie Ventimiglia ◽  
...  
Keyword(s):  
Overall Survival ◽  
Relapse Rate ◽  
Cumulative Incidence ◽  
Relapse Free Survival ◽  
Hematopoietic Stem ◽  
Free Survival ◽  
Allogeneic Hsct ◽  
Gvhd Prophylaxis ◽  
Reduced Intensity

Abstract Introduction: Patients with AML and MDS who are age 60 or above represent a discrete group of patients with a different disease biology compared to younger patients. These patients are often not offered allogeneic hematopoietic stem cell transplant (HSCT) as a curative intent because of concern of increased nonrelapse mortality (NRM) and poor overall survival (OS). Hence, the information on transplant outcomes among this population is very limited. Recently with the use of better supportive care measures and reduced intensity preparative regimens, patients greater than 60 are often recommended to proceed to transplant. This study evaluates our single center experience of allogeneic transplantation in patients with MDS and AML aged 60 and older. Patients and Methods: We retrospectively evaluated 60 years or older consecutive patients with AML and MDS who underwent allogeneic HSCT between January 2005 and December 2014. The primary objectives of our study were to determine NRM, relapse, relapse free survival (RFS) and OS at 1 year following transplant. The secondary objectives were to estimate cumulative incidence of acute (aGVHD) and chronic GVHD (cGVHD) at 1 year, length of stay and readmission rate in the first 100 days following transplant. Results: Between January 2005 and December 2014, 159 patients underwent allogeneic HSCT with the median age of 64 (range, 60-75) years and median follow-up duration for OS of 3.34 (95% CI, 2.51-3.87) years. Increasing number of patients were transplanted in recent years, i.e., 67% patients between 2010-2014 compared to 33% between 2005-2009. One hundred three patients (65%) had AML and 56 patients (35%) had MDS. Forty-nine patients (31%) received full intensity regimen and 110 patients (69%) received reduced intensity regimen. Fifty-two patients (33%) underwent allogeneic related transplant and 107 patients (67%) had allogeneic unrelated transplant. Thymoglobulin based GVHD prophylaxis was given in 77 patients (48%) whereas non-thymoglobulin based GVHD prophylaxis was given in 82 patients (52%). The median day to neutrophil and platelet engraftment was 11 (range, 7-22) days and 16 (range, 0-675) days, respectively. Graft failure occurred in 3 patients. At 1-year follow-up, the cumulative incidence of grade II-IV aGVHD was 39.7% (95% CI, 32.0-47.2%), grade III-IV aGVHD was 20.8% (95% CI, 14.9-27.5%) and cGVHD was 54.1% (95% CI, 46.0-61.5%). The cumulative incidence of chronic extensive GVHD was 39.8% (95% CI, 32.1-47.4%). Blood stream infection, cytomegalovirus reactivation, Epstein-Barr virus reactivation, C. difficile diarrhea occurred in 44%, 35%, 22% and 26% of patients, respectively. At 1-year follow-up, NRM was 25.3% (95% CI, 18.8-32.3%), RFS was 53.3% (95% CI, 46.1-61.7%), relapse rate was 21.4% (95% CI, 15.4-28.1%) and OS was 56.4% (95% CI, 49.2-54.7%). The median day of hospitalization following transplant was 26 (range, 19-112) days and almost half (52%) of patients were readmitted in the first 100 days following transplant. Leukemia recurrence was the most common cause of death. Multivariable analysis demonstrated high disease risk index to be the independent predictor of poor RFS, OS and higher relapse rate (p<0.03), whereas non-thymoglobulin based GVHD prophylaxis, higher comorbidity index (≥3) and MDS were found to be associated with higher NRM (p<0.03). Most importantly, age did not shown to have any effect on relapse rate, OS, RFS, or NRM. Conclusion: Our results indicate that allogeneic HSCT is well tolerated and had acceptable NRM, and OS among this group. Hence, older age alone should not be considered a contraindication to HSCT. Figure 1 Overall survival (OS) and relapse-free survival (RFS) estimates. The median OS is 1.60 years (95% CI, 0.94 to 5.00 years) and the median RFS is 1.15 years (95% CI, 0.63 to 3.07 years). The median follow-up time of OS and RFS are 3.34 years (95% CI, 2.51 to 3.87 years) and 3.25 years (95% CI, 2.51 to 3.87 years), respectively. Figure 1. Overall survival (OS) and relapse-free survival (RFS) estimates. The median OS is 1.60 years (95% CI, 0.94 to 5.00 years) and the median RFS is 1.15 years (95% CI, 0.63 to 3.07 years). The median follow-up time of OS and RFS are 3.34 years (95% CI, 2.51 to 3.87 years) and 3.25 years (95% CI, 2.51 to 3.87 years), respectively. Figure 2 Cumulative incidences of aGVHD, cGVHD, relapse and non-relapse mortality after transplantation. Figure 2. Cumulative incidences of aGVHD, cGVHD, relapse and non-relapse mortality after transplantation. Disclosures Deol: Jazz Pharmaceuticals: Consultancy.

scholarly journals CD34+Selected Hematopoietic Stem Cell Transplants Conditioned with a Myeloablative Regimen Is Well Tolerated and Results in Good Outcomes in Patients with Myelofibrosis

Blood ◽  
2018 ◽  
Vol 132 (Supplement 1) ◽  
pp. 4636-4636
Author(s):  
Jeong-Ok Lee ◽  
Jessica Flynn ◽  
Molly Maloy ◽  
Ann A. Jakubowski ◽  
Esperanza B. Papadopoulos ◽  
...  
Keyword(s):  
Stem Cell ◽  
Cumulative Incidence ◽  
Acute Gvhd ◽  
Systemic Treatment ◽  
Chronic Gvhd ◽  
Relapse Free Survival ◽  
Hematopoietic Stem ◽  
Free Survival ◽  
Gvhd Prophylaxis ◽  
Grade Ii

Abstract Background: Allogeneic hematopoietic stem cell transplantation (Allo-HSCT) remains the only curative treatment for myelofibrosis (MF). Due to high incidence of non-relapse mortality (NRM) in patients with MF who underwent allo-HCT with myeloablative conditioning (MAC), transplants in these patients are mostly done by utilizing a reduced intensity conditioning regimen with calcineurin inhibitors for graft versus host disease (GVHD) prophylaxis. We previously published very good outcomes in patients with acute leukemia (AML and ALL) and myelodysplastic syndrome (MDS) who underwent Ex- vivo CD34+-selected T-cell depleted (TCD) allo-HSCT following MAC regimens (Barba P et al. BBMT 2017; Tamari R et al. BBMT 2018). Aim: To study retrospectively the outcomes of patients with primary or secondary myelofibrosis (PMF or SMF) who underwent a CD34+ cell-selected Allo-HSCT. Methods: Twenty-one MF patients who underwent a CD34+-selected Allo-HSCT at a single center between October 2010 and November 2017 were included in this retrospective analysis. All patients received MAC regimen including busulfan, melphalan and fludarabine and antithymocyte globulin to prevent graft rejection. None of the patients received post-transplant GVHD prophylaxis. G-CSF mobilized peripheral blood stem cell grafts were depleted of T-cells using immunomagnetic CD34+ selection by CliniMACS device. Overall survival (OS), relapse free survival (RFS), relapse, NRM and the composite endpoint of GVHD-free/relapse-free survival (GFRS: defined as grade 3-4 acute GVHD, chronic GVHD requiring systemic treatment, relapse, or death) were estimated using the Kaplan-Meier and cumulative incidence method, with death considered a competing risk for relapse. Log-rank and Gray's tests were used to assess differences in patient and treatment characteristics. Results: Patient's and donor's characteristics are summarized in table 1. Neutrophils engraftment occurred in all patients at a median of 11 days (range: 8 - 14) and 90% (N = 19) achieved platelet engraftment at a median of 24 days (range, 14 - 77). Another patient achieved platelet engraftment only after splenectomy which was performed on post-transplant day 54. With a median follow-up of 54.06 months, the estimated 3-year OS and RFS were 84.4 % (95% CI, 69.6% to >99.9%) and 74.7% (95% CI, 57.6 to 96.9%), respectively (figure 1). The cumulative incidence of grade II-IV acute GVHD at day 100 was 33.3% (95% CI 11.2-54.1%); majority (N=5) had grade II and 2 patients had grade III (N=1) and grade IV (N=1) acute GVHD. Chronic GVHD developed in 2 patients including only 1 case requiring systemic treatment. The 3-year cumulative incidence rate of relapse was 9.5% (95% CI, <0.1 to 22.4%); three relapse cases include 2 patients with molecular/cytogenetic relapse and 1 patient with clinical relapse. Patients who relapsed were treated with donor lymphocyte infusion (DLI) (N=1), with azacytidine plus DLI (N=1) and both are alive with minimal molecular disease. The 3rd patient is alive without evidence of disease recurrence 43 months after second unmodified Allo-HSCT from the original donor. NRM at 3 years was 15.6% (95% CI, <0.1% to 32.4%) and the cause of all deaths (n=3) was primarily attributed to acute GVHD. The estimated 3-year GRFS was 66.7% (95% CI, 49.3 to 90.2%) (figure 2). TCD boost and unmodified boost were conducted successfully for patients with poor graft function (N=1) and late graft failure (N=1). Six patients received 8 DLIs for the following indications: mixed chimerism (N=3), relapse (N=3) and poor immune reconstitution (N=2). Conclusions: In this analysis we demonstrate that CD34+ selected Allo-HSCT following a chemotherapy only based MAC regimen is well-tolerated and an effective treatment for patients with myelofibrosis. We noted higher incidence of acute GVHD when compared to our reported outcomes in patients with acute leukemia and MDS undergoing a CD34+ selected allo-HSCT and all cases of mortality in this analysis were secondary to GVHD. This may suggest differences in the biology of the diseases and a more inflammatory milieu in pts with MF. Relapse incidence was notably low and all patients who relapsed were salvaged with further cellular therapy suggesting a strong graft-versus-leukemia effect in this disease. Disclosures Sauter: Juno Therapeutics: Consultancy, Research Funding; Sanofi-Genzyme: Consultancy, Research Funding; Spectrum Pharmaceuticals: Consultancy; Novartis: Consultancy; Precision Biosciences: Consultancy; Kite: Consultancy. Perales:Incyte: Membership on an entity's Board of Directors or advisory committees, Other: Personal fees and Clinical trial support; Novartis: Other: Personal fees; Merck: Other: Personal fees; Takeda: Other: Personal fees; Abbvie: Other: Personal fees.

scholarly journals Phase III Randomized Study of 4 Weeks of High-Dose Interferon-α-2b in Stage T2bNO, T3a-bNO, T4a-bNO, and T1-4N1a-2a (microscopic) Melanoma: A Trial of the Eastern Cooperative Oncology Group–American College of Radiology Imaging Network Cancer Research Group (E1697)

2017 ◽  
Vol 35 (8) ◽  
pp. 885-892 ◽  
Author(s):  
Sanjiv S. Agarwala ◽  
Sandra J. Lee ◽  
Waiki Yip ◽  
Uma N. Rao ◽  
Ahmad A. Tarhini ◽  
...  
Keyword(s):  
Quality Of Life ◽  
Eastern Cooperative Oncology Group ◽  
High Dose ◽  
Intermediate Risk ◽  
Oncology Group ◽  
Relapse Free Survival ◽  
Free Survival ◽  
Risk Melanoma ◽  
High Dose Interferon

Purpose To test the efficacy of 4 weeks of intravenous (IV) induction with high-dose interferon (IFN) as part of the Eastern Cooperative Oncology Group regimen compared with observation (OBS) in patients with surgically resected intermediate-risk melanoma. Patients and Methods In this intergroup international trial, eligible patients had surgically resected cutaneous melanoma in the following categories: (1) T2bN0, (2) T3a-bN0, (3) T4a-bN0, and (4) T1-4N1a-2a (microscopic). Patients were randomly assigned to receive IFN α-2b at 20 MU/m2/d IV for 5 days (Monday to Friday) every week for 4 weeks (IFN) or OBS. Stratification factors were pathologic lymph node status, lymph node staging procedure, Breslow depth, ulceration of the primary lesion, and disease stage. The primary end point was relapse-free survival. Secondary end points included overall survival, toxicity, and quality of life. Results A total of 1,150 patients were randomly assigned. At a median follow-up of 7 years, the 5-year relapse-free survival rate was 0.70 (95% CI, 0.66 to 0.74) for OBS and 0.70, (95% CI, 0.66 to 0.74) for IFN ( P = .964). The 5-year overall survival rate was 0.83 (95% CI, 0.79 to 0.86) for OBS and 0.83 (95% CI, 0.80 to 0.86) for IFN ( P = .558). Treatment-related grade 3 and higher toxicity was 4.6% versus 57.9% for OBS and IFN, respectively ( P < .001). Quality of life was worse for the treated group. Conclusion Four weeks of IV induction as part of the Eastern Cooperative Oncology Group high-dose IFN regimen is not better than OBS alone for patients with intermediate-risk melanoma as defined in this trial.

Sign in / Sign up

Export Citation Format

Share Document