Busulfan (Bu) Plus Cyclophosphamide (Cy) Versus TBI Plus Cy Conditioning for Allogeneic Stem Cell Transplantation (alloSCT) From Matched Unrelated Donors (MUD) In Adult Patients with AML in First Relapse: A Survey From the Acute Leukemia Working Party of EBMT

Blood ◽  
2011 ◽  
Vol 118 (21) ◽  
pp. 161-161 ◽  
Author(s):  
Arnon Nagler ◽  
Myriam Labopin ◽  
Avichai Shimoni ◽  
Jürgen Finke ◽  
Dietrich Beelen ◽  
...  
Keyword(s):  
Acute Gvhd ◽  
Conflicts Of Interest ◽  
Working Party ◽  
Risk Groups ◽  
Adult Patients ◽  
Free Survival ◽  
Unrelated Donors ◽  
Conditioning Regimens ◽  
First Relapse

Abstract Abstract 161 TBY/Cy and Bu/Cy are the standard myeloablative conditioning regimens for alloSCT in adults with AML. Whether, one is associated with better outcomes compared to the other in the setting of relapsed AML is not well described. We therefore compared TBI/Cy to Bu/Cy conditioning prior to alloSCT in 158 adult patients (pts) with AML in first relapse (Rel 1) that underwent alloSCT from HLA matched (6/6) unrelated donors. 83 patients were given TBI/Cy and 75 Bu/Cy. The median age was 38 years (range, 19–62) in the TBI/Cy vs. 42 years (19–72) in the Bu/Cy group (P<0.012). FAB classifications, cytogenetic risk, time from diagnosis to alloSCT, donor gender and CMV serostatus were not different between the 2 groups. Median year of alloSCT was 2004 vs. 2007 (P<0.0001) for the TBI/Cy vs. Bu/Cy groups, respectively. Conditioning included ATG in 31% vs. 67% in the TBI/Cy and Bu/Cy groups, respectively (P<0.001). 78% of the Bu/Cy group and 80% of the TBI/Cy group, received PBSC grafts, while 22% and 20% received BM grafts, respectively (P=0.8). Median follow-up was, 23 months (range, 1–125) in TBI/Cy and 21 months (1–119) in Bu/Cy. The engraftment rate was similar between both groups with ANC>500/μL achieved at a median of 17 (10–33) and 16 (6–31) days in the TBI/Cy and Bu/Cy groups, respectively (P=0.23). Similarly, acute GVHD (≥Gr II) incidence did not differ between the 2 groups: 33% vs. 37% for the TBI/Cy vs. Bu/Cy, respectively. Death before day 100 occurred in 38% vs. 25% with TBI/Cy vs. Bu/Cy, respectively (P=0.25). 2- year NRM was similar between the 2 groups, 31±5% vs. 21±5%, respectively (P=0.15). In addition, the 2-year relapse rate did not differ between the 2 groups: 50±4% vs. 50±6%, respectively (P=0.93). Leukemia-free survival (LFS) at 2 years, was also similar between the TBI/Cy vs. Bu/Cy groups: 18 ± 5% vs. 29 ± 6 %, respectively (P=0.10). However, overall survival (OS) was significantly higher with Bu/Cy vs. TBI/Cy 38±6% vs. 21±4%, respectively (P=0.02). The main cause of death was disease relapse: 53% and 60%, with TBI/Cy vs. Bu/Cy, respectively (p=0.49). Of note, there were no differences in death from organ toxicities including VOD between the 2 groups. The rate of infection-related deaths did not differ between the groups, as well, 19% vs. 11% (p=0.25). In multivariate analysis, age, cytogenetic risk groups, use of ATG and interval from diagnosis to alloSCT were not significant prognostic factors for survival. In all, these results suggest that in AML patients in Rel 1 undergoing myeloablative alloSCT, Bu/Cy and TBI/Cy conditioning regimens can lead to similar outcomes including GVHD, NRM, disease progression and LFS. However, in terms of OS, there is a suggestion for an advantage in favor of the Bu/Cy regimen possibly due to a lower overall toxicity and improved capacity for salvage therapy. Disclosures: No relevant conflicts of interest to declare.

Treatment with Hypomethylating Agents before Allogeneic Stem Cell Transplant Improves Survival for Patients with Chronic Myelomonocytic Leukemia

Blood ◽  
2015 ◽  
Vol 126 (23) ◽  
pp. 4347-4347 ◽  
Author(s):  
Piyanuch Kongtim ◽  
Uday R. Popat ◽  
Antonio M. Jimenez ◽  
Sameh Gabella ◽  
Riad O. El Fakih ◽  
...  
Keyword(s):  
Acute Gvhd ◽  
Chronic Gvhd ◽  
Progression Free Survival ◽  
Cell Transplant ◽  
Hypomethylating Agents ◽  
Hematopoietic Stem ◽  
Free Survival ◽  
Unrelated Donors ◽  
Conditioning Regimens

Abstract Introduction Allogeneic hematopoietic stem cell transplant (allo-SCT) is the only curative treatment modality for patients with CMML. Here we retrospectively reviewed the data for patients with CMML who received an all-SCT at our institution to identify factors associated with improved survival and determine whether treatment with hypomethylating agents (HMA) before transplant improves survival for these patients. Methods All 83 patients 18 years of age or older with a diagnosis of CMML confirmed at The University of Texas MD Anderson Cancer Center who underwent allo-SCT between April 1991 and December 2013 were identified through review of the institutionÕs medical records and included in this analysis. Forty, 7, and 36 patients had CMML-1, CMML-2 and CMML that had progressed to AML (CMML/AML) respectively. The median age was 57 years. CMML specific cytogenetic risk at diagnosis (Such E, hematologica, 2011) was good, intermediate, and high risk in 46, 19, and 18 patients respectively. Seventy-eight patients received induction treatment before transplant, 37 receiving HMA (either 5-azacytidine or decitabine) for at least 3 courses and 41 receiving 1-2 courses of cytotoxic chemotherapy. Among the patients who received induction therapy, 15 patients in HMA group and 9 patients in convention chemotherapy group achieved a complete remission before transplant. Thirty, 47 and 6 patients received transplants from matched related donors (MRD), matched unrelated donors (MUD), and mismatched related or unrelated donors (MMD), respectively. The sources of hematopoietic stem cells were peripheral blood for 48 patients (57.8%) and bone marrow for 35 patients (42.2%). Conditioning regimens varied; most patients received either fludarabine in combination with busulfan or fludarabine combined with melphalan. Sixty-four patients received myeloablative and 19 patients received reduced intensity conditioning regimens. Graft-versus-host disease (GVHD) prophylaxis consisted of tacrolimus and methotrexate. Patient and transplant characteristics did not significantly differ between the patients treated with HMA and the patients treated with conventional chemotherapy or given supportive care alone. The primary endpoint was progression-free survival (PFS). The secondary endpoints were overall survival (OS), Treatment related mortality (TRM), relapse incidence through last follow-up and incidences of acute GVHD and chronic GVHD. All of these outcomes were measured from the time of allo-SCT. Results Median follow up duration for 29 survivors was 48 months. Seventy-five patients engrafted (90.4%) with median time to neutrophil and platelet engraftment of 13 and 15 days respectively. Patients treated with a HMA had a significantly lower cumulative incidence (CI) of relapse at 3 years post-transplant (22%) than those treated with other agents (35%; p=0.03), whereas TRM at 1 year post-transplantdid not significantly differ between the groups (27% and 30%, respectively; p=0.84). Acute GVHD all grades and grade 2-4 were seen in 28.2% versus 35.8% (p=0.05) and 12.8% versus 11.3% (p=0.72) in patients who received a HMA compared to those who treated with other agents respectively. CI of chronic GVHD was 35% in patients treated with a HMA versus 19.2% in those treated with other agents (p=0.36) while CI of chronic extensive GVHD was seen in only 26.7% versus 19.2% respectively (p=0.64). The lower relapse rate resulted in a significantly higher 3-year PFS rate in patients treated with a HMA (43%) than in those who received other treatments (27%; p=0.04) (Figure 1). However, therapy with HMA before transplant did not significantly influence the 3-year OS rate (45% in those treated with HMA and 39% in those treated with other agents; p=0.22). The independent prognostic factors for PFS were a blast count of < 5% before transplant (HR 0.36, 95%CI 0.14-0.78), treatment with a HMA (HR 0.44, 95% CI 0.23-0.86), a transplant from an MRD (HR 0.41, 95% CI 0.22-0.94), development of grade 2-4 acute GVHD (HR 2.7, 95% CI 1.27-5.77), and development of chronic GVHD (HR 0.15, 95% CI 0.05-0.45). Conclusion We conclude that treatment with hypomethylating agents before allo-SCT may improve survival in patients with CMML. Figure 1. Progression free survival Figure 1. Progression free survival Disclosures Alousi: Therakos, Inc: Research Funding. Andersson:Otsuka Research and Development, Inc.: Consultancy.

Nonmyeloablative Conditioning and Hematopoietic Cell Transplantation (HCT) from HLA-Matched Related or Unrelated Donors for Chemotherapy-Refractory Chronic Lymphocytic Leukemia (CLL).

Blood ◽  
2004 ◽  
Vol 104 (11) ◽  
pp. 2323-2323
Author(s):  
Mohamed Sorror ◽  
Michael Maris ◽  
Barry Storer ◽  
Brenda Sandmaier ◽  
Monic Stuart ◽  
...  
Keyword(s):  
Overall Survival ◽  
Acute Gvhd ◽  
Disease Free Survival ◽  
Cerebral Stroke ◽  
Phase Ii Trials ◽  
Free Survival ◽  
Increased Risk ◽  
Unrelated Donors ◽  
Disease Free

Abstract Sixty-four patients (pts) with chemotherapy-refractory CLL who were ineligible for ablative allogeneic HCT due to age and/or comorbidities were given nonablative-HCT from related (n=44) or unrelated donors (n=20) between 1997-2003 (Table). Median pt age was 56 (range 44–69) years, interval from diagnosis to HCT was 4.4 (3–25) years, and number of prior regimens was 4 (range 1–12). Sixty-one pts were refractory to at least 1 regimen, 56 to fludarabine (FLU), 19 to alkylating agents, 14 to rituxumab and 4 to CAMPATH, and 2 had failed autologous HCT. Twenty-three pts (36%) had disease responsive to last chemotherapy [28% partial (PR) and 8% complete remission (CR)] while 34 were nonresponsive and 7 had untested relapse. Conditioning for HCT consisted of 2 Gy TBI alone (n=11) or combined with FLU (n=53), 90 mg/m2. Postgrafting immunosuppression consisted of mycophenolate mofetil and cyclosporine. Pts received G-CSF mobilized peripheral blood mononuclear cells. After HCT, pts became neutropenic for a median of 11 days. Forty-four percent of pts had thrombocytopenia (&lt;20,000 cells/ul). Three pts had graft rejection; 1 died with aplasia and 2 are alive with disease relapse. Incidences of grades II, III, and IV acute GVHD were 39%, 14%, and 2% respectively, and chronic GVHD was 50% at 2-years. With median follow up of 24 (range 2.8–62.8) months, the overall response rate was 67% (50% in CR). URD-pts had significantly higher CR rate than MRD-pts. All 11 responding patients tested had molecular eradication of their disease. Overall, 39 patients are alive; 25 in CR, 5 in PR, 2 with stable disease, and 7 with relapse/progression. Twenty-five pts died, 10 from progression, 10 from infections ± GVHD, 2 from cardiac causes, 1 from metastatic lung cancer, 1 from cerebral stroke and 1 from rejection and aplasia. Estimated 2-year rates of non-relapse mortality, disease free survival, and overall survival were 22%, 52%, and 60% respectively. In multivariate analysis, high pretransplant comorbidity scores predicted higher non-relapse mortality and worse survival while bulky lymphadenopathy predicted increased risk of progression. CLL appears susceptible to graft-versus-leukemia effects particularly after URD grafts and nonablative-HCT should be explored in phase II trials in pts with FLU-refractory CLL. Table: Results Related (n = 44) Unrelated (n = 20) P Acute GVHD grade II, III, and IV 39%, 11%, and 2% 40%, 20%, and 0% 0.41 2-year chronic extensive GVHD 44% 69% 0.56 Median follow up (range) 31 (3–63) months 12 (3–39) months CR at 2-years 42% 78% 0.005 Relapse/progression at 2 years 34% 5% 0.08 Surviving pts 13 CR, 3 PR, 2 stable, 5 progression, 1 relapse 12 CR, 2 PR, 1 relapse 2-year non-relapse mortality 22% 20% 0.75 2-year disease free survival 44% 75% 0.15 2-year overall survival 56% 74% 0.33

Comparison of Low Dose Total Body Irradiation (TBI)-Based Reduced Intensity Conditioning (RIC) Vs. Chemotherapy-Based RIC Prior to Allogeneic Stem Cell Transplantation (allo-SCT) From An HLA Identical Sibling Donor for Acute Myeloid Leukemia (AML) in First Complete Remission (CR1): a Retrospective Analysis of 1200 Patients From the Acute Leukemia Working Party of EBMT.

Blood ◽  
2009 ◽  
Vol 114 (22) ◽  
pp. 1190-1190 ◽  
Author(s):  
Mohamad Mohty ◽  
Myriam Labopin ◽  
Jeroen JWM Janssen ◽  
Ghulam J Mufti ◽  
J. J. Cornelissen ◽  
...  
Keyword(s):  
Median Time ◽  
Low Dose ◽  
Conflicts Of Interest ◽  
Working Party ◽  
Risk Groups ◽  
Sibling Donor ◽  
Related Risk ◽  
Retrospective Nature ◽  
Total Body

Abstract Abstract 1190 Poster Board I-212 RIC is increasingly used in allo-SCT for AML patients. RIC allo-SCT represents an attempt to harness the immune graft-versus-leukemia effect while attempting to control or overcome toxicity. Most of the RIC protocols have been shown to be highly immunosuppressive, but because of the variability in the degree of myeloablation, the toxicity and efficacy profiles might vary from one protocol to another. Low dose TBI in RIC is frequently used, however it is still unknown whether outcomes are different when comparing low dose TBI-based RIC and chemotherapy-based RIC regimens. Moreover, some transplant centres do not have radiation facilities. Therefore, the aim of this study was to compare outcomes (leukemia-free survival: LFS, Non-Relapse Mortality: NRM, and relapse incidence) between patients receiving a low dose TBI-based RIC vs. chemotherapy-based RIC prior to allo-SCT from an HLA identical sibling donor for AML in CR1. Between 2000 and 2008, 323 patients with AML in CR1 were treated with low dose TBI-based RIC (Fludarabine + TBI) and 877 received a chemotherapy-based RIC (including fludarabine in the majority of cases), and reported to the EBMT Registry. All patients received allogeneic PBSC from HLA-identical sibling donors. Patients receiving TBI-based RIC were older (median 56 y. vs. 54 y.; p<0.0001), but the median time from diagnosis to allo-SCT was shorter (143 days vs. 163 d.; p<0.0001) in the TBI group. Both groups were comparable in terms of period (median year: 2005) of allo-SCT, donor-recipient gender distribution, and CMV serostatus. In terms of AML-related risk factors, WBC (median: 9600/μL), the cytogenetics risk groups (good: 4.1%; intermediate: 81.5%; and poor: 14.4%), and the FAB subtype (M1-M2: 48.8%; M4-M5: 36.4%; M0-M6-M7: 14.4%) at diagnosis, were also comparable between both groups. The median time to engraftment (ANC>500/μL) was comparable between both groups (15 vs. 16 days, p=NS). With a median follow-up of 15 (range, 0.3-107) months, 2 years LFS were 50±3%, 53±2% in the TBI-based RIC and chemo based RIC groups respectively (p=0.16). Also, at 2 years, the relapse incidence was not significantly associated with the type of RIC regimen: 37±3%, 34±2% in the TBI-based RIC and chemo-based RIC groups respectively (p=0.17). Finally, NRM was also comparable between both groups [21±3% and 20±2% in the TBI-based RIC and chemo-based RIC groups respectively; p=0.60) Despite its retrospective nature, results from this large study suggest that RIC allo-SCT is a valid option for AML patients not eligible for standard allo-SCT. The overall outcomes (LFS, NRM and relapse) appear not to be significantly different between AML patients in CR1 receiving a low dose TBI-based RIC allo-SCT versus those receiving a chemotherapy-based RIC allo-SCT using an HLA-identical sibling donor. Disclosures: No relevant conflicts of interest to declare.

scholarly journals Post-Transplant Cyclophosphamide Versus MTX-CSA As Gvhd Prophylaxis in HLA-Identical Sibling HSCT

Blood ◽  
2018 ◽  
Vol 132 (Supplement 1) ◽  
pp. 3394-3394
Author(s):  
Rebeca Bailén ◽  
Maria-Jesús Pascual ◽  
Pascual Balsalobre ◽  
Anabel Gallardo-Morillo ◽  
Abel García-Sola ◽  
...  
Keyword(s):  
Cumulative Incidence ◽  
Acute Gvhd ◽  
Conflicts Of Interest ◽  
Conditioning Regimen ◽  
High Dose ◽  
Hematopoietic Stem ◽  
Free Survival ◽  
Post Transplant ◽  
Gvhd Prophylaxis

Abstract Background: Post-transplant high dose cyclophosphamide (PT-CY) effectively prevents graft-versus-host disease (GVHD) after HLA-haploidentical hematopoietic stem cell transplantation (HSCT). However, the use of PT-CY in HLA-identical HSCT is less explored. In this study, we analyzed the results of PT-CY as GVHD prophylaxis in HLA-identical sibling HSCT and compared them with those obtained after prophylaxis with methotrexate (MTX) plus cyclosporine (CsA). Methods: 107 HLA-identical sibling (10/10) HSCT from 2 Spanish centers have been analyzed: 50 performed consecutively between 2010 and 2015 using MTX-CsA as GVHD prophylaxis, and 57 performed consecutively between 2014 and 2018 using PT-CY. Results: Baseline characteristics and post-transplant complications are shown in Table 1. GVHD prophylaxis consisted in MTX days +1, +3, +6 and +11, and CsA from day -1 in the MTX-CsA group. The PT-CY group received cyclophosphamide 50 mg/kg/d on days +3 and +5 in 38 patients (65%), combined with CsA from day +5, and cyclophosphamide on days +3 and +4 in 19 patients (35%), followed by CsA and mycophenolate mofetil from day +5. Graft source was PBSC in 96% in the MTX-CsA group and 86% in the PT-CY group. Conditioning regimen was myeloablative in 64% and 40%, respectively. Neutrophil and platelet engraftment was significantly delayed in the PT-CY group (14.5 (11-27) vs 15.5 (13-37), p=0.02; 11.5 (8-180) vs 20.5 (10-43), p=0.02). After a median follow-up of 60 months for the MTX-CsA group and 15 months for the PT-CY group, 2-year overall survival (OS) was 56% (42-70) and 78% (67-90) (p=0.088), and event-free survival (EFS) was 48% (34-62) and 62.5% (42.5-82.5) (p=0.054), respectively. Cumulative incidence at 100 days of grade II-IV (52.2% vs. 22.6%, p=0.0015), and III-IV (24.4% vs. 8.8%, p=0.016) acute GVHD were significantly higher in the MTX-CsA group (Figure 1A). No differences were observed in the 2-year cumulative incidence of chronic moderate to severe GVHD (26% vs. 16.7% (p=0.306)). No differences were observed in the 2-years cumulative incidence of relapse (27% vs. 28% (p=0.47)). Non-relapse mortality (NRM) at 2-years showed a higher trend in the MTX-CsA cohort (24% vs. 8.8%, p=0.054). Finally, the composite endpoint of GVHD and relapse-free survival (GRFS) at 2-years was significantly better in the PT-CY group (48% vs. 24%, p=0.011) (Figure 1B). Conclusions: In our experience, GVHD prophylaxis using PT-CY combined with additional immunosuppression after HLA-identical sibling HSCT, using mostly peripheral blood as graft source, reduced the cumulative incidence of acute GVHD compared to standard prophylaxis with MTX-CsA, leading to an impact on GRFS. To our knowledge, this is the largest comparative retrospective cohort reported. Further prospective studies with longer follow-up are needed to confirm these observations. Disclosures No relevant conflicts of interest to declare.

scholarly journals Role of Allogeneic Stem Cell Transplantation (AlloSCT) in Patients Affected By Peripheral T-Cell Lymphomas (PTCL): No Difference in Outcome Between Patients Allografted at Diagnosis and in First Chemosensitive Relapse

Blood ◽  
2014 ◽  
Vol 124 (21) ◽  
pp. 2574-2574 ◽  
Author(s):  
Anna Dodero ◽  
Francesco Spina ◽  
Franco Narni ◽  
Francesca Patriarca ◽  
Fabio Benedetti ◽  
...  
Keyword(s):  
T Cell ◽  
Partial Remission ◽  
Conflicts Of Interest ◽  
Long Term Outcome ◽  
Free Survival ◽  
T Cell Lymphomas ◽  
Significant Difference ◽  
First Relapse ◽  
Peripheral T Cell Lymphomas

Abstract Introduction: Despite novel therapies are under investigation in peripheral T-cell lymphomas (PTCL), the majority of the patients (pts) still have a dismal outcome. AlloSCT seems an effective approach in the salvage setting, but very small series of pts have been transplanted at diagnosis. Methods: We report the long-term outcome (median follow-up of 60 months) of 72 pts affected by PTCL who underwent AlloSCT at diagnosis (Allo1) (n=23) or for chemosensitive relapse (Allo2) (n=49) that have been enrolled in two transplantation protocols. Pathological classification included: 20 PTCL-not otherwise specified (PTCL-NOS), 2 anaplastic large cell lymphoma (ALCL) and 1 rare subtype in Allo1 group; 18 PTCL-NOS, 11 ALCL, 8 AILD and12 rare subtypes in Allo2 group. Donor sources were HLA-matched siblings [n=39: n=13 Allo1 and n=26 Allo2 (p=0.80)], matched or mismatched unrelated donors [n=25: n=10 Allo1 and n=15 Allo2 (p=0.30], and haploidentical family donors [n=8, only in the Allo2 group]. All pts underwent transplant with chemosensitive disease: 45 in complete remission (CR) (63%) [n=20 Allo1, n=25 Allo2 (p=0.003)]; 27 in partial remission (PR) (37%) [n=3 Allo1, n=24 Allo2 (p=0.003)]. In the Allo2 group, 37 pts (75%) were allografted in first relapse and 12 in second relapse. Results: In the Allo1 group, at a median follow-up of 59 months, of the 23 pts 15 (65%) are alive in CR, 4 (17%) died for progressive disease (PD), 3 for non-relapse mortality (NRM, 13%) and 1 for myocardial infarction. In the Allo2 group, at a median follow-up of 64 months, of the 49 pts 31 (63%) are alive (29 in CR), 11 (22%) died for PD and 6 (12%) for NRM while 1 for a second cancer. Five years crude cumulative incidence of relapse was 18% and 38% in Allo1 and Allo2 group (p=0.11), respectively. Five-year relapse-free survival (RFS), progressive-free-survival (PFS), and overall-survival (OS) were as follows: 80%, 60% and 62%, respectively, in Allo1 group; 61%, 47%and 59%, respectively, in Allo2 group without any statistical difference. However, we observed a significant difference in PFS between pts allografted at diagnosis and those in second-relapse (5-year PFS 61% versus 16%, p=0.0044) but not between the allografted at diagnosis and first-relapse (5-year PFS 61% versus 57%, p=0.92). When analyzed pts affected by PTCL-NOS, a better PFS trend was confirmed in pts receiving allograft at diagnosis or in first relapse as compared to second relapse [5-year PFS: 65% versus 55% versus 25%, respectively, (p=0.2)]. Pts who went to alloSCT in first CR did not have a significant advantage [5-year PFS and OS: 59% versus 43% (p=0.44); 60% versus 58% (p=0.82) in Allo1 and Allo2 group, respectively]. Conclusions: Despite the limitations due to the sample size, this is the first analysis in this setting. AlloSCT should be not indicated as a consolidation of first complete or partial remission approach/treatment outside a clinical trial. In fact, AlloSCT is very effective in patients with chemosensitive first relapse. Disclosures No relevant conflicts of interest to declare.

Event free survival in adults with relapsed ALL who underwent front-line therapy with CALGB 10403.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. e19005-e19005
Author(s):  
Suravi Raychaudhuri ◽  
Ilana Yurkiewicz ◽  
Gabriel N. Mannis ◽  
Bruno C. Medeiros ◽  
Steve E. Coutre ◽  
...  
Keyword(s):  
Overall Survival ◽  
Cohort Study ◽  
Survival Time ◽  
Retrospective Cohort Study ◽  
Retrospective Cohort ◽  
Event Free Survival ◽  
Front Line ◽  
Free Survival ◽  
First Relapse

e19005 Background: CALGB 10403 is a pediatric-inspired ALL regimen that has recently been shown to have improved survival rates in adolescents and young adults with ALL when compared to historical outcomes with traditional adult ALL regimens (Stock et. al, 2019). Methods: This is a retrospective cohort study of ALL patients who received induction CALGB 10403 at Stanford University (both on and off trial), achieved CR1, and subsequently relapsed. Primary outcome of interest was event free survival from time of diagnosis. Events were defined as relapse or death. Secondary outcomes were overall survival and event free survival from first relapse. Patients were censored at time of last clinical follow up. Results: 25 patients met inclusion criteria and received front-line CALGB 10403 from April 2010 to September 2018. At the time of initial diagnosis median age was 30 years (range 18 – 39 years). 68% of patients were male. 48% of patients were overweight and 40% were obese. 76% of patients had precursor B cell ALL while 24% had T cell ALL. 12% had CNS disease at diagnosis. 36% of patients had WBC greater than 30k. 12% of patients had CRLF2 rearrangement. 12% of patients were MRD positive after first induction. 20% of patients received rituximab. Median event free survival time from diagnosis was 20 months (range 3 – 79 months) and median overall survival time was 53 months. Blinatumomab was the most common salvage therapy after 1st relapse, followed by inotuzumab. 15 patients (60%) achieved CR2, of which 4 (27%) were MRD positive after 2nd induction. 15 patients (60%) went to HSCT. Of the patients who achieved CR2, 8 relapsed for a second time. Median event free survival time after first relapse was 23 months. Survival 1 year after relapse was 60%. 11 of the 25 patients were alive at last follow up. Median follow up time of survivors was 6 years. Conclusions: This is a descriptive retrospective cohort study of adult patients in a real world setting who received CALGB 10403 induction and subsequently relapsed. Compared to other studies of relapsed ALL patients who were induced with traditional chemotherapy (Fielding et. al, 2007), survival 1 year after relapse was much higher (60% vs. 22%). As CALGB 10403 becomes an increasingly common induction regimen for AYA and adults with ALL, further outcomes study is required.[Table: see text]

Efficacy of avelumab plus axitinib (A + Ax) versus sunitinib (S) by number of IMDC risk factors and tumor sites at baseline in advanced renal cell carcinoma (aRCC): Extended follow-up results from JAVELIN Renal 101.

2021 ◽  
Vol 39 (6_suppl) ◽  
pp. 302-302
Author(s):  
Yoshihiko Tomita ◽  
Robert J. Motzer ◽  
Toni K. Choueiri ◽  
Brian I. Rini ◽  
Hideaki Miyake ◽  
...  
Keyword(s):  
Risk Factors ◽  
Objective Response ◽  
Progression Free Survival ◽  
Final Analysis ◽  
Risk Groups ◽  
Phase Iii ◽  
Once Daily ◽  
Free Survival ◽  
To Receive

302 Background: In the phase III JAVELIN Renal 101 trial (NCT02684006), A + Ax demonstrated progression-free survival (PFS) and objective response rate (ORR) benefit across IMDC risk groups (favorable, intermediate, and poor) vs S in patients with previously untreated aRCC. Here we report efficacy of A + Ax vs S by number of IMDC risk factors (0, 1, 2, 3, and 4-6) and target tumor sites (1, 2, 3, and ≥4) at baseline from the second interim analysis of overall survival (OS). Methods: Patients were randomized 1:1 to receive A 10 mg/kg intravenously every 2 wk + Ax 5 mg orally twice daily or S 50 mg orally once daily for 4 wk (6-wk cycle). PFS and ORR per independent central review (RECIST 1.1) and OS were assessed. Results: At data cut-off (Jan 2019), median (m) follow-up for OS and PFS was 19.3 vs 19.2 mo and 16.8 vs 15.2 mo for the A + Ax vs S arm, respectively. The table shows OS, PFS, and ORR by number of IMDC risk factors and target tumor sites at baseline. A + Ax generally demonstrated efficacy benefit vs S across subgroups. Conclusions: With extended follow-up, A + Ax generally demonstrated efficacy benefit vs S across the number of IMDC risk factors and tumor sites at baseline in aRCC. OS was still immature; follow-up for the final analysis is ongoing. Clinical trial information: NCT02684006 . [Table: see text]

scholarly journals Nonmyeloablative Allogeneic Stem-Cell Transplantation for Hematologic Malignancies: A Systematic Review

2003 ◽  
Vol 10 (1) ◽  
pp. 17-41 ◽  
Author(s):  
Benjamin Djulbegovic ◽  
Jerome Seidenfeld ◽  
Claudia Bonnell ◽  
Ambuj Kumar
Keyword(s):  
Stem Cell ◽  
Case Series ◽  
Disease Status ◽  
Hematologic Malignancies ◽  
Cell Transplants ◽  
Unrelated Donors ◽  
Conditioning Regimens ◽  
Prospective Case Series ◽  
Patient Selection Criteria

Background Increasingly, clinicians advocate the use of nonmyeloablative allogeneic stem-cell transplants (NM-allo-SCTs, “mini-transplants”) to manage hematologic malignancies. They hypothesize that NM-allo-SCT is equally efficacious to standard allo-SCT but produces less regimen-related toxicity. Methods To analyze available evidence on the benefits and harms of “mini-transplants,” we identified 23 manuscripts, 1 abstract, and 1 letter that reported the outcome of mini-transplants in hematologic malignancies. Results Data were compiled on 603 treated patients, with 118 transplants using stem cells from matched unrelated donors. All studies were small prospective case series, and most lacked concurrent or historical controls. Outcomes of interest were not uniformly reported. The studies were heterogeneous and used different patient selection criteria, conditioning regimens, and timing of transplant with respect to disease status. The transplant-related mortality rate was 32%, the relapse rate was 15%, and toxicities included acute and chronic graft-vs-host disease and veno-occlusive disease. The aggregate rate of complete remission was 45%. Survival at 1 year or longer ranged from 30% to 60% at 1 to 5 years of follow-up. All studies reported successful chimerism. Conclusions Disease-specific studies with longer follow-up are needed to evaluate this potentially promising therapy.

Comparison of Outcomes After Allogeneic HSCT for Adult Patients with AML in Remission Using in the Conditioning Regimen Either I.V. Busulfex (BU) Plus Cyclophosphamide (Cy) or TBI Plus Cy: An- ALWP-EBMT Survey.

Blood ◽  
2009 ◽  
Vol 114 (22) ◽  
pp. 195-195
Author(s):  
Arnon Nagler ◽  
Myriam Labopin ◽  
Avichai Shimoni ◽  
Liisa Volin ◽  
Donald W. Bunjes ◽  
...  
Keyword(s):  
Conflicts Of Interest ◽  
Conditioning Regimen ◽  
Disease Status ◽  
Post Transplantation ◽  
Allogeneic Hsct ◽  
Reduce Relapse Rate ◽  
Conditioning Regimens ◽  
Wbc Count ◽  
Transplantation Outcomes

Abstract Abstract 195 TBI/CY and oral (p.o) Bu/Cy are the traditional allogeneic HSCT (alloHSCT) myeloablative conditioning regimens for adults with AML with comparable survival and relapse probabilities. Intravenous (i.v.) Bu in contrast to p.o Bu has more predictable pharmacokinetics and a more favorable toxicity profile. Post transplantation outcomes with i.v. Bu/Cy, thus, may be superior to those achieved with TBI/Cy. In order to address these issues, the ALWP of the EBMT performed a survey comparing i.v. Bu/Cy to TBI/Cy as conditioning regimen for adult pts. with AML undergoing alloHSCT. Overall, 603 alloHSCT were analyzed. One hundred pts. underwent alloHSCT with Bu/Cy while 503 with TBI/Cy. Age was 41 (range, 18–57) and 41 (range, 16–61) years and median transplant year was 2004 (2000 – 2005) and 2003 (2000 – 2005) for the Bu/Cy and TBI/Cy groups, respectively. Disease status at alloHSCT were CR1 – 81% vs. 78% and CR2–19% vs. 22% for the Bu/Cy and TBI/Cy groups, respectively. WBC count at diagnosis was 11×109/L and 15×109/L, respectively. Regarding the cytogenetic classification, 10% and 10% were good, 60% and 55% were intermediate and 9% and 6% were poor risk, respectively (data were NA for 21%–26% of pts). Sixty nine percent and 68% of both groups underwent alloHSCT from sibling donors, while 31% and 32% from MUD, respectively. Length of follow up was 37(15–86) and 57 (1–105) months for both groups, respectively. Sixty nine percent and only 41% of the Bu/Cy and TBI/Cy groups received PB, while 31% and 59% received BM grafts, respectively (p<0.0001). Engraftment was similar in the Bu/Cy vs. the TBI/Cy groups, 95% and 96%, respectively. Cumulative incidence of TRM at 2y was 17+4% and 23+2%, respectively (p=0.23). Acute GVHD (II–IV) was also similar between the 2 groups, 28% and 32%, respectively. Two year relapse incidence was 30+5% and 22+2% for Bu/Cy vs. TBI/Cy, respectively (p=0.03) while LFS was comparable 57+5% and 61+2%, respectively (p=0.5). In multivariate analysis Cy/TBI was found to be an independent good prognostic factor for reduce relapse rate (p=0.03, HR-1.67) and there was a trend for higher TRM (p=0.16). Poor prognostic factors for LFS and TRM were age >40y, disease status (CR2 vs. CR1) and MUD vs. Sib. donor. In conclusion, in this retrospective EBMT survey outcomes of alloHSCT in adult pts. with AML in CR using either i.v Bu/Cy or TBI/Cy were comparable. Disclosures: No relevant conflicts of interest to declare.

One Antigen HLA-Mismatched Related and 8/8 Allele Matched Unrelated Donors Are Associated with Similar Survival after Hematopoietic Cell Transplantation for Acute Leukemia.

Blood ◽  
2008 ◽  
Vol 112 (11) ◽  
pp. 965-965
Author(s):  
David Valcarcel ◽  
Fangyu Kan ◽  
Tao Wang ◽  
Stephanie J. Lee ◽  
Stephen R Spellman ◽  
...  
Keyword(s):  
Acute Gvhd ◽  
Chronic Gvhd ◽  
Conditioning Regimen ◽  
Disease Free Survival ◽  
Unrelated Donor ◽  
Free Survival ◽  
Gvhd Prophylaxis ◽  
Unrelated Donors ◽  
Related Donor ◽  
Disease Free

Abstract Patients in need of an allogenetic hematopoietic cell transplant but who lack an HLA genotypically identical sibling donor, are faced with the decision to consider a single HLA antigen mismatched related donor, or a search for a suitable 8/8 matched unrelated donor. We compared the outcomes of adult patients (≥18 years old) receiving a transplant for the treatment of AML or ALL in first or second remission from either a one-antigen mismatched related donor (MMRD group, N=89) reported to the CIBMTR or an 8/8 HLA-A, B, C and DRB1 allele matched unrelated donor (UD group, N=700) facilitated by the NMDP between 1995–2005. MMRD group was typed by serological or DNA-based methods for HLA-A, -B and –DR with all results verified by lab report review. The UD group was retrospectively typed for HLA-A, B, C and DRB1 by high resolution typing methods. Most received myeloablative conditioning regimens (77%), calcineurin inhibitor-based GVHD prophylaxis (100%) and T cell replete grafts (100%). 13% received ATG with the conditioning regimen. Median follow-up was 54 and 38 months in the MMRD and UD groups, respectively. The MMRD group was younger (median age 35 vs 43, p=0.002), had more ALL patients with low-risk cytogenetics (43% vs 18%, p=0.005), had older donors (median age: 38 vs 34, p=0.047), were more likely to receive methotrexate for GVHD prophylaxis (89% vs 77%, p=0.014) and were more likely to be transplanted prior to 2001 (62% vs 24%; p<0.001). There were no differences in patient or donor gender, diagnosis, disease-status, cytogenetic-risk of AML, time from diagnosis to transplant, stem cell source, conditioning regimen, use of ATG and Karnofsky index. Univariate comparisons (MMRD vs. UD) showed: 3-year OS (42% vs 44%, p=0.647), 3-year DFS (41% vs 41%, p=0.931), 3-year TRM (39% vs 31%, p=0.136), 3-year incidence of relapse (20% vs 28%, p=0.094), grade III–IV acute GVHD by 100 days (22% vs. 15%, p=0.147), chronic GVHD by 1 year (35% vs 47%, p=0.029). All multivariate analyses were adjusted for patient and transplant characteristics and are shown in the table below. In summary, transplants utilizing one-antigen mismatched related and 8/8 allele-matched unrelated donors did not significantly differ in overall survival or disease free survival, but chronic GVHD was more frequent after UD transplantation. Outcome RR (MMRD vs. UD) 95% CI p-value Survival 0.99 0.73–1.34 0.94 Disease-free survival 1.06 0.80–1.41 0.69 Treatment related mortality 1.14 0.77–1.69 0.52 Relapse 0.81 0.50–1.30 0.38 Acute GVHD III–IV 1.53 0.91–2.57 0.11 Chronic GVHD 0.58 0.39–0.85 0.006

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