Equivalent Outcome Between Reduced Intensity Versus Conventional Myeloablative Conditioning Hematopoietic Stem Cell Transplantation for Patients Older Than 35 Years with Acute Myeloid Leukemia.

Blood ◽  
2012 ◽  
Vol 120 (21) ◽  
pp. 3103-3103
Author(s):  
Marie Sebert ◽  
Raphaël Porcher ◽  
Marie Robin ◽  
Lionel Ades ◽  
Emmanuel Raffoux ◽  
...  
Keyword(s):  
Myeloid Leukemia ◽  
Research Funding ◽  
Cox Regression ◽  
Karnofsky Performance Status ◽  
Performance Status ◽  
Conditioning Regimen ◽  
Hematopoietic Stem ◽  
Treatment Related Mortality ◽  
Related Mortality

Abstract Abstract 3103 Introduction: Allogeneic Hematopoietic Stem Cell Transplantation (HSCT) provides the best chance of long-term survival for patients with intermediate or high-risk acute myeloid leukemia (AML). The major limitation of this procedure is the risk of treatment related mortality (TRM). Use of reduced intensity conditioning (RIC) regimen has become standard practice among older candidates with comorbidities. Although RIC regimen have been used for over a decade in older patients, the benefit of this approach in younger patients with AML compared with the risk of toxicity of standard regimen (MAC) is still discussed. We compared the outcomes for patients with AML over 35 years using RIC or MAC HSCT. Patients, methods, and transplantation characteristics: From January 2000 to December 2010, 132 consecutive patients older than 35 years with AML (18 secondary AML) received HSCT in our center, either from siblings (n=87) or HLA 10/10 allele-matched donors (n=45). MAC (n=72) and RIC (n=60) regimens were defined as previously described (Bacigalupo, 2009). Seventy-three patients were in first complete remission (CR1); 30% of patients had poor risk cytogenetics (MRC classification). Karnofsky performance status was scored at time of HSCT. Engraftment, acute and chronic graft-versus-host disease (GvHD), transplantation-related mortality (TRM), relapse rate as well as overall survival (OS) at 4 years were compared according to the intensity of the conditioning regimen. First a classical multivariable Cox analysis was conducted. In a second step, baseline confounding factors were adjusted for using inverse probability-of-treatment weighting (IPTW). Results of the comparison: Patient characteristics according to the intensity of the conditioning regimen were similar for AML type (de novo versus secondary), gender, karnofsky performance status, CR#, donor type and number of CD34+ infused. Particularly, cytogenetic risks were comparable in both groups. Patients were younger in the MAC group (median age 44 years [range 35 to 56 years] vs 54[37 to 66] for RIC, p<0,0001), received mainly bone marrow as source of stem cells (54% versus 2% for RIC, p<0,0001) and GvHD prophylaxis using cyclosporine plus methotrexate (89% versus 5% for RIC, p<0,0001). Moreover, ATG in the conditioning regimen (more ATG in RIC: 51 vs. 14%, p<0.0001), donor age (older for RIC: 49 vs. 39 years, p=0.002) and number of nucleated cells infused (higher in RIC: 11 vs. 4 × 108/kg, p<0.0001) were also different. The median follow-up was 47 months (10 to 134), and 25% of patients had a follow-up of at least 74 months. During evolution, all patients engrafted. The cumulative incidence (CIf) of acute GVHD grade II-IV was 49% (35% after RIC vs 61% after MAC, p=0.001). The 5-year CIf of chronic GVHD was 37% (40% after RIC vs 30% after MAC, p=0.32). During FU, 71 patients died. The 5-year CIf of TRM was 21% (13% after RIC vs 28% after MAC, p=0.009). Adjusting for cytogenetic risk, gender donor/recipient mismatch and infused nucleated cells, no difference was observed between RIC and MAC (HR 0.9, p=0.16). The 5-year CIf of relapse was 42% (51% after RIC vs 35% after MAC (p=0.22)). Adjusting for gender donor/recipient mismatch, donor/recipient CMV serostatus and infused CD34+ cells, no marked difference was observed between RIC and MAC (HR 0.8, 95%CI 0.4–1.5, p=0.50). The 5-year OS was 39% (50% after RIC vs 34% after MAC, p=0.38). Using both Cox regression and IPTW to account for imbalance in patients characteristics, similar OS was found after RIC and MAC (Figure 1), with adjusted HRs for MAC vs RIC of 0.9 (95%CI 0.4–1.8, p=0.68) with Cox regression and 0.9 (95%CI 0.4–1.8, p=0.76) with IPTW. Conclusion: In patients with AML over 35 years, MAC regimen lead to a non significant higher rate of treatment related mortality with no benefit in terms of relapse when compared with RIC regimen. Until prospective trials are completed, this study supports the use of a RIC regimen for patients with AML older than 35 years who are transplanted either from siblings or matched unrelated donors. Disclosures: Fenaux: Amgen: Honoraria, Research Funding; Celgene: Honoraria, Research Funding; Janssen: Honoraria, Research Funding; Roche: Honoraria, Research Funding; GSK: Honoraria, Research Funding; Novartis: Honoraria, Research Funding.

scholarly journals Allogeneic Hematopoietic Stem Cell Transplantation in Patients with Acute Myeloid Leukemia and Karnofsky Performance Status Score Equal or Lower Than 80%. a Study from the Acute Leukemia Working Party (ALWP) of the European Society for Blood and Marrow Transplantation (EBMT)

Blood ◽  
2019 ◽  
Vol 134 (Supplement_1) ◽  
pp. 2038-2038 ◽  
Author(s):  
Francesco Saraceni ◽  
Myriam Labopin ◽  
Edouard Forcade ◽  
Nicolaus Kröger ◽  
Gerard Socie ◽  
...  
Keyword(s):  
Acute Myeloid Leukemia ◽  
Stem Cell ◽  
Myeloid Leukemia ◽  
Research Funding ◽  
Karnofsky Performance Status ◽  
Performance Status ◽  
Chronic Gvhd ◽  
Hematopoietic Stem ◽  
Reduced Risk ◽  
Acute Myeloid

Thanks to the recent developments in transplant procedures, an increasing number of patients with acute myeloid leukemia (AML) with a poor Karnofsky Performance Status (KPS) score are currently offered an allogeneic hematopoietic stem cell transplantation (allo-HCT). Nevertheless, little data is available about outcome of this fragile population. We report here the results of a retrospective study designed to evaluate outcome of patients with AML undergoing allo-HCT with KPS score ≤80%. The analysis included patients with AML aged ≥18 years, undergoing allo-HCT in first remission between 2000 and 2018, with a KPS score at the time of transplant between 50% and 80%. Patients who received manipulated grafts or had incomplete data about cytogenetics were excluded. Conditioning intensity was defined according to EBMT definitions. A total of 2,963 patients were identified. Median age at transplant was 55 years (18-77 years). Median year of transplant was 2014. The KPS score was =80% in 85% of the patients and <80% in 15% of the patients. Cytogenetic risk was good, intermediate or poor in 6%, 68% and 26% of the patients, respectively. Donor type was sibling (MSD), matched (10/10 UD), mismatched (9/10 UD) unrelated, haploidentical (haplo) or cord blood (CB) in 47%, 35%, 8%, 6% and 4% of patients, respectively. Conditioning was myeloablative (MAC) or reduced-intensity (RIC) in 42% and 58% of patients. Stem cell source was PBSC or BM in 84% and 14% of the patients. Anti-thymocyte globulin (ATG) was administered to 55% of the patients. Cumulative incidence of grade II-IV and III-IV acute GVHD (aGvHD) was 26% and 8%, respectively. The 2-year cumulative incidence of chronic GVHD (cGvHD) and severe cGVHD was 38% and 18%. Non-relapse mortality (NRM) and relapse incidence (RI) at 2 years were 19% and 27%, respectively. Notably, in the subgroup of patients with KPS <80% NRM rate was as high as 27%. At 2 years, leukemia-free survival (LFS), overall survival (OS) and GVHD-free, relapse-free survival (GRFS) rates were 54%, 59% and 41%, respectively. On multivariate analysis, transplant from a MSD was associated with a reduced risk of aGvHD (10/10 UD HR 1.8, 9/10 UD HR 2.4, haplo HR 1.9, CB HR 3.4, p<10-4, MSD as reference) and NRM (10/10 UD HR 1.4, 9/10 UD HR 2.4, haplo HR 1.8, CB HR 2, p<10-3, MSD as reference) as compared to all other donor types (Table 1). Transplant from 10/10 UD was associated with lower GRFS (HR 1.2, p=0.03), while 9/10 UD predicted inferior LFS, OS and GRFS (HR 1.6, 1.7, and 1.5, respectively, p<0.001) as compared to MSD. Patients with KPS score of 80% had significantly lower NRM and improved survival as compared to patients with KPS score <80% (NRM: HR 0.6, p<10-4; OS: HR 0.7, p<10-4). Other factors independently associated with improved OS were younger age, female sex, good or intermediate risk cytogenetics and de-novo AML. Notably, administration of ATG was associated with reduced risk of developing grade II-IV aGVHD (HR 0.7, p<10-4), cGVHD (HR 0.6, p<10-4), severe cGVHD (HR 0.5, p<10-4) and predicted improved GRFS (HR 0.8, p<0.01). In order to compare outcome following MAC and RIC conditioning the analysis was restricted to patients receiving transplant from MSD or UD. Patients with a KPS score =80% or <80% were analyzed separately. In the group of patients with a KPS score of 80%, a RIC regimen was associated with higher RI (HR 1.4, p<0.01), higher incidence of severe cGVHD (HR 1.6, p<0.001), and inferior GRFS (HR 1.3, p<0.001) as compared to MAC. NRM was not significantly different following RIC or MAC in this population. In contrast, in patients with a KPS score <80%, RIC was associated with lower NRM (HR 0.3, p<0.0001) and better LFS (HR 0.6, p<0.01), OS (HR 0.5, p<0.0001) and GRFS (HR 0.6, p<0.01) as compared to MAC. In conclusion, allo-HCT is feasible in patients with acute myeloid leukemia in first remission and KPS score <80%, with acceptable NRM and survival rates. As for the conditioning regimen, in patients with a KPS score of 80% a MAC regimen was associated with lower relapse rate, similar NRM and better GRFS as compared to RIC, while in patients with a KPS score lower than 80% RIC was associated with reduced NRM and improved OS as compared to MAC. In addition, transplant from a MSD predicted a reduced risk of NRM and aGVHD as compared to other donor types. Notably, 9/10 UD was associated with significantly inferior survival as compared to MSD. Finally, administration of ATG correlated with reduced acute and chronic GVHD and improved GRFS. Disclosures Labopin: Jazz Pharmaceuticals: Honoraria. Kröger:Sanofi-Aventis: Research Funding; Celgene: Honoraria, Research Funding; DKMS: Research Funding; JAZZ: Honoraria; Medac: Honoraria; Neovii: Honoraria, Research Funding; Novartis: Honoraria, Research Funding; Riemser: Research Funding. Socie:Alexion: Consultancy. Blaise:Pierre Fabre medicaments: Honoraria; Jazz Pharmaceuticals: Honoraria; Sanofi: Honoraria; Molmed: Consultancy, Honoraria. Byrne:Ariad/Incyte: Honoraria, Speakers Bureau. Esteve:Astellas: Consultancy, Speakers Bureau; Novartis: Consultancy, Research Funding, Speakers Bureau; Celgene: Consultancy, Speakers Bureau; Amgen: Consultancy; Daiichi Sankyo: Consultancy; Jazz Pharmaceuticals: Consultancy; Roche: Consultancy; Pfizer: Consultancy. Mohty:Jazz Pharmaceuticals: Honoraria, Research Funding.

scholarly journals Clinical Outcomes Following Treatment with Gilteritinib or Quizartinib in Patients with Relapsed/Refractory FLT3-ITD+ Acute Myeloid Leukemia

Blood ◽  
2020 ◽  
Vol 136 (Supplement 1) ◽  
pp. 42-43
Author(s):  
Alexander E. Perl ◽  
Qiaoyang Lu ◽  
Alan Fan ◽  
Nahla Hasabou ◽  
Erhan Berrak ◽  
...  
Keyword(s):  
Acute Myeloid Leukemia ◽  
Complete Remission ◽  
Myeloid Leukemia ◽  
Research Funding ◽  
Phase 3 ◽  
Hematopoietic Stem ◽  
Travel Costs ◽  
Baseline Characteristics ◽  
Acute Myeloid

Background: Gilteritinib is approved for patients (pts) with relapsed/refractory (R/R) FLT3-mutated acute myeloid leukemia (AML), based on findings from the phase 3 ADMIRAL trial (Perl AE, et al. N Engl J Med. 2019). A phase 3 trial, QuANTUM-R, demonstrated the benefit of quizartinib in pts with R/R AML with FLT3 internal tandem duplication (FLT3-ITD) mutations (Cortes JE, et al. Lancet Oncol. 2019). Although eligibility criteria across both studies were similar, QuANTUM-R was more stringent as to prior therapy intensity and remission duration, which potentially enriched for higher-risk pts. We sought to describe outcomes from ADMIRAL among pts who otherwise met eligibility for QuANTUM-R. Methods: In this post-hoc analysis, a subset of pts from ADMIRAL were matched with R/R FLT3-ITD+ AML pts from QuANTUM-R on the basis of baseline characteristics and prior treatment criteria. Matched pts were either refractory to initial anthracycline-based chemotherapy or had relapsed ≤6 mos after achieving composite complete remission (CRc) with an anthracycline-based regimen. Results: Overall, 218 pts with R/R FLT3-ITD+ AML in the ADMIRAL trial (gilteritinib, n=140; salvage chemotherapy [SC], n=78) were matched with the QuANTUM-R intention-to treat (ITT) population (N=367; quizartinib, n=245; SC, n=122). Proportions of pts preselected for high-intensity SC were 66% (n=143/218) in the matched ADMIRAL ITT population and 77% (n=281/367) in the QuANTUM-R ITT populations. Demographic and baseline characteristics of the matched ADMIRAL ITT population and QuANTUM-R ITT population were similar. Median durations of exposure to gilteritinib and quizartinib were 3.8 mos and 3.2 mos, respectively, and median number of treatment cycles received were five and four, respectively. Rates of hematopoietic stem cell transplantation (HSCT) were similar in pts treated with gilteritinib (35%; n=49/140) or quizartinib (32%; n=78/245), as were the proportions of pts who resumed gilteritinib (23%; n=32/140) or quizartinib (20%; n=48/245) therapy post-HSCT. Median overall survival (OS) in pts treated with gilteritinib or quizartinib was longer than that observed with SC. After a median follow-up of 17.4 mos, median OS was 10.2 mos with gilteritinib versus 5.6 mos with SC (hazard ratio [HR]=0.573 [95% CI: 0.403, 0.814]; one-sided nominal P=0.0008). After a median follow-up of 23.5 mos, median OS with quizartinib was 6.2 mos versus 4.7 mos with SC (HR=0.76 [95% CI: 0.58-0.98]; one-sided P=0.02). After censoring for HSCT, median OS was 9.3 mos with gilteritinib versus 5.5 mos with SC (HR=0.525 [95% CI: 0.356-0.775]; nominal one-sided P=0.0005), and 5.7 mos versus 4.6 mos with quizartinib versus SC, respectively (HR=0.79 [95% CI: 0.59, 1.05]; one-sided P=0.05). In both QuANTUM-R and matched ADMIRAL populations, the survival benefits of quizartinib and gilteritinib compared with SC were maintained across multiple subgroups, including high FLT3-ITD allelic ratio subsets. Compared with SC, high CRc rates were observed in pts treated with either gilteritinib (57%; n=80/140) or quizartinib (48%; n=118/245). The complete remission (CR) rate with gilteritinib was 23% (n=32/140), whereas the CR rate with quizartinib was 4% (n=10/245) (Table). Median time to achieve CRc was 1.8 mos with gilteritinib and 1.1 mos with quizartinib, median duration of CRc was 5.5 mos with gilteritinib and 2.8 mos with quizartinib. The safety profiles of gilteritinib and quizartinib were generally similar, though aspartate or alanine aminotransferase elevations (any grade) were more frequent with gilteritinib (41-44%) than quizartinib (≤13%), whereas neutropenia (14% vs 34%, respectively), fatigue (24% vs 39%, respectively), and prolonged QT intervals (9% vs 27%, respectively) were more frequent with quizartinib. Conclusions: In pts with R/R FLT3-ITD+ AML and similar baseline characteristics, both gilteritinib and quizartinib were generally well tolerated and associated with improved survival and treatment response compared with SC. Responses to gilteritinib and quizartinib, as measured by CRc, were similar; blood count recovery varied between the two FLT3 inhibitors. Although cross-study comparisons have substantial limitations, the findings suggest that while remission is achieved faster with quizartinib, response may be more durable and survival potentially longer with gilteritinib. Disclosures Perl: Syndax: Consultancy, Honoraria; Leukemia & Lymphoma Society, Beat AML: Consultancy; Novartis: Honoraria, Other, Research Funding; Agios: Consultancy, Honoraria, Other; Jazz: Honoraria, Other; FORMA Therapeutics: Consultancy, Honoraria, Other; Daiichi Sankyo: Consultancy, Honoraria, Other: Writing/editorial support, travel costs for meetings, Research Funding; FUJIFILM Pharmaceuticals USA, Inc: Research Funding; New Link Genetics: Honoraria, Other; Arog Pharmaceuticals Inc: Other: uncompensated consulting, travel costs for meetings; Actinium Pharmaceuticals Inc: Consultancy, Honoraria, Research Funding; Biomed Valley Discoveries: Research Funding; Astellas: Consultancy, Honoraria, Other: writing/editorial support, travel costs for meeting presentations related to study, Research Funding; Bayer HealthCare Pharmaceuticals: Research Funding; AbbVie Inc: Consultancy, Honoraria, Other, Research Funding; Takeda: Honoraria, Other: Travel costs for meeting; Loxo Oncology Inc, a wholly owned subsidiary of Eli Lilly & Company: Consultancy, Honoraria, Other. Lu:Astellas: Current Employment. Fan:Astellas Pharma: Current Employment. Hasabou:Astellas Pharma: Current Employment. Berrak:Astellas: Current Employment. Tiu:Eli Lilly & Company: Current equity holder in publicly-traded company, Ended employment in the past 24 months; Astellas Pharma Global Development: Current Employment.

Radiosurgery for parasagittal and parafalcine meningiomas

2013 ◽  
Vol 119 (4) ◽  
pp. 871-877 ◽  
Author(s):  
Dale Ding ◽  
Zhiyuan Xu ◽  
Ian T. McNeill ◽  
Chun-Po Yen ◽  
Jason P. Sheehan
Keyword(s):  
Cox Regression ◽  
Karnofsky Performance Status ◽  
Performance Status ◽  
Tumor Control ◽  
Who Grade ◽  
Tumor Control Rate ◽  
Karnofsky Performance Status Score ◽  
Status Score ◽  
Performance Status Score

Object Parasagittal and parafalcine (PSPF) meningiomas represent the second most common location for intracranial meningiomas. Involvement of the superior sagittal sinus or deep draining veins may prevent gross-total resection of these tumors without significant morbidity. The authors review their results for treatment of PSPF meningiomas with radiosurgery. Methods The authors retrospectively reviewed the institutional review board–approved University of Virginia Gamma Knife database and identified 65 patients with 90 WHO Grade I parasagittal (59%) and parafalcine (41%) meningiomas who had a mean MRI follow-up of 56.6 months. The patients' mean age was 57 years, the median preradiosurgery Karnofsky Performance Status score was 80, and the median initial tumor and treatment volumes were 3 and 3.7 cm3, respectively. The median prescription dose was 15 Gy, isodose line was 40%, and the number of isocenters was 5. Kaplan-Meier analysis was used to determine progression-free survival (PFS). Univariate and multivariate Cox regression analyses were used to identify factors associated with PFS. Results The median overall PFS was 75.6 months. The actuarial tumor control rate was 85% at 3 years and 70% at 5 years. Parasagittal location, no prior resection, and younger age were found to be independent predictors of tumor PFS. For the 49 patients with clinical follow-up (mean 70.8 months), the median postradiosurgery Karnofsky Performance Status score was 90. Symptomatic postradiosurgery peritumoral edema was observed in 4 patients (8.2%); this group comprised 3 patients (6.1%) with temporary and 1 patient (2%) with permanent clinical sequelae. Two patients (4.1%) died of tumor progression. Conclusions Radiosurgery offers a minimally invasive treatment option for PSPF meningiomas, with a good tumor control rate and an acceptable complication rate comparable to most surgical series.

scholarly journals Preliminary Outcomes of Children and Young Adults with Acute Lymphoblastic Leukaemia and Down Syndrome (DS-ALL) on UKALL 2011. Reduction in Treatment-Related Mortality with De-Escalated Therapy

Blood ◽  
2018 ◽  
Vol 132 (Supplement 1) ◽  
pp. 656-656
Author(s):  
Sara Ghorashian ◽  
Sujith Samarasinghe ◽  
Amy A Kirkwood ◽  
Rachael Hough ◽  
Clare Rowntree ◽  
...  
Keyword(s):  
Down Syndrome ◽  
Acute Lymphoblastic Leukaemia ◽  
Research Funding ◽  
Advisory Board ◽  
Drug Induction ◽  
Risk Patients ◽  
The Uk ◽  
Treatment Related Mortality ◽  
Related Mortality

Abstract Introduction Reported outcomes for children with Downs syndrome (DS) and acute lymphoblastic leukaemia (ALL) treated on our previous national study, UKALL 2003, were inferior compared to non-DS children. 5 year event free survival (EFS) for DS children was 65.6% vs. 87.7% for non-DS children and 5 year overall survival (OS) was 70.0% vs. 92.2% (British Journal of Haematology 2014; 165: 552-555). Excess treatment related mortality (TRM, 21.6% vs. 3.3% at 5 years) in children with DS-ALL was primarily due to infection. Similar results have been reported by other study groups. In our successor study, UKALL 2011, we employed several steps of de-escalation for DS-ALL patients compared to standard therapy. Here, we report that de-escalated therapy has resulted in a dramatic reduction in TRM for children with DS-ALL treated in the UK. Methods DS-ALL patients treated on UKALL 2011 had their treatment modified in the following respects: 1)NCI high risk patients did not receive anthracycline in induction unless they had a slow early response at day 15; 2) two years maintenance was given for both boys and girls; 3) no pulses were given in maintenance for MRD low risk patients. In addition, we recommended use of prophylactic antibiotics during induction and intensive phases of treatment. Fisher's exact test was used to compare induction mortality in the DS and non-DS pts. OS was defined as time from registration to death. EFS was defined as time from registration to first event (induction failure, relapse, second malignancy or death from any cause). The Kaplan-Meier method was used for survival estimation. Results The UKALL 2011 trial opened to recruitment on 26th April 2012 and has recruited 2362 patients, of whom 50 have Down syndrome, in the period up to 22nd February 2018. The study is open in 41 centres in UK and Ireland and included patients with both ALL and lymphoblastic lymphoma (LBL). The baseline characteristics of the patients recruited up to this date are shown in the table below. For DS-ALL, Day 29 MRD was available for 48 patients and was low risk in 25 cases (50%), risk in 19 (38 %) and no result was obtained in 4 (8 %). The therapy was generally well-tolerated, there have been no cases of therapy curtailment due to toxicity and only one patient due to receive intensified therapy per MRD risk assessment was unable to escalate due to toxicity. At a median follow-up of 32.7 months, there have been 4 events. These include two relapses (relapse rate: 4.1% (1.1-15.5) at 3 years) and two TRMs (one TRM in induction and the other in consolidation; both due to infection). Three year EFS is: 92.9% (95% CI: 79.1 - 97.7) with a three year OS of 95.9% (84.5 - 99.0). The remarkably low induction TRM for DS children on UKALL 2011 (1 death out of 50 patients, 2%), is comparable to that of non-DS children treated on the same protocol with a 3 drug induction (12 out of 1174 children, 1% induction TRM; induction TRM in DS-ALL vs non-DS-ALL p=0.42). It is also comparable to the induction TRM in DS-ALL noted in the latter half of the UKALL 2003 study (1/40, 2.5%) when the aforementioned treatment modifications were first implemented in the UK. Importantly, this TRM is a quarter of that when an historic cohort of DS-ALL children were treated with a 4-drug induction on our previous study (UKALL 2003, DS-ALL TRM 4/46 patients i.e. 8 %, p=0.19). Conclusion These preliminary results suggest that de-escalation of treatment is successful in reducing treatment related mortality for children with DS-ALL without increasing the risk of early relapse, however longer term follow-up is needed. Disclosures Ghorashian: Celgene: Other: travel support; Novartis: Honoraria. Hough:University College London Hospital's NHS Foundation Trust: Employment. Kearns:Pfizer: Consultancy, Research Funding; Galen: Research Funding. Vora:Jazz: Other: Advisory board; Medac: Other: Advisory board; Pfizer: Other: Advisory board; Amgen: Other: Advisory board; Novartis: Other: Advisory board.

scholarly journals Allogeneic Hematopoietic Stem Cell Transplantation in Patients Older than 65 Years with Acute Myeloid Leukemia and Myelodysplastic Syndrome: A 15-Year Experience

2021 ◽  
Author(s):  
Simona Piemontese ◽  
Lorenzo Lazzari ◽  
Annalisa Ruggeri ◽  
Magda Marcatti ◽  
Maria Teresa Lupo Stanghellini ◽  
...  
Keyword(s):  
Stem Cell ◽  
Karnofsky Performance Status ◽  
Performance Status ◽  
Conditioning Regimen ◽  
Disease Free Survival ◽  
Consecutive Series ◽  
Cell Transplant ◽  
Hematopoietic Stem ◽  
Matched Donor ◽  
Acute Myeloid

Abstract Background. Median age of occurrence of acute myeloid leukemias (AML) and myelodisplastc syndromes (MDS) is 65 years and older. Nevertheless, the use of allogeneic stem cell transplant (allo-HCT) has been historically limited to younger population, namely due to excess in non-relapse-mortality (NRM) in olders. Methods. In the present study, we analyzed all consecutive patients aged ≥ 65y diagnosed with AML (71, 81%) or MDS (19, 19%) who received transplants from adult donors at our center from January 2005 to December 2019. Results. Median age was 68.29y (65.02-76.54), 26pts (29%) aged ≥ 70y. Thirty-three (37%) pts received a HLA-matched donor. Conditioning regimen was myeloablative in 46pts (51%). The 3-year overall survival (OS) was 53+/-6%, and disease free survival (DFS) 45+/-6% (Figure 1). Day-100 and 3-year NRM was 17+/-2% and 29+/-2%, respectively. The 3-year CI of relapse was 22+/-2%. Day-100 CI of aGvHD was 21+/-2% for grade II-IV, 14+/-1% for grade III-IV. The 3-year CI of cGvHD was 35+/-3%, extensive 20+/-2%. In multivariate analysis, the Karnofsky Performance Status (KPS) < 90% was associated with lower OS (HR: 2.999, CI: 1.477- 6.691; p=0.002), DFS (HR: 3.155, CI: 1.593 - 6.250; p=0.001) and higher NRM (HR: 2.997, CI: 1.344-6.682; p=0.041). HCT-CI ≥ 3 was also associated with higher NRM (HR: 2.949, CI: 1.166-7.462, p=0.022,). Diagnosis of MDS and receiving a matched donor with PTCy were associated with longer OS (HR: 0.3440, CI: 0.1029-0.915; p=0.033; HR: 0.197, CI: 0.042-0.934; p=0.041).Conclusions. Age alone should not limit transplant eligibility for AML and MDS. KPS and HCT-CI proved to be useful for patient selection among the elderly. The use of HLA-matched donors with PTCy improved OS compared to ATG in our consecutive series.

scholarly journals Allogeneic Hematopoietic Stem Cell Transplantation in Patients with Acute Lymphoblastic Leukemia and Karnofsky Performance Status Score Equal or Lower Than 80%. a Study from the Acute Leukemia Working Party (ALWP) of the European Society for Blood and Marrow Transplantation (EBMT)

Blood ◽  
2019 ◽  
Vol 134 (Supplement_1) ◽  
pp. 3327-3327
Author(s):  
Francesco Saraceni ◽  
Myriam Labopin ◽  
Riitta Niittyvuopio ◽  
Gerard Socie ◽  
Nicolaus Kröger ◽  
...  
Keyword(s):  
Stem Cell ◽  
Acute Lymphoblastic Leukemia ◽  
Research Funding ◽  
Karnofsky Performance Status ◽  
Lymphoblastic Leukemia ◽  
Performance Status ◽  
Chronic Gvhd ◽  
Hematopoietic Stem ◽  
First Remission ◽  
Grade Ii

Recently, an increasing number of patients with acute lymphoblastic leukemia with a poor Karnofsky Performance Status (KPS) score are considered for allogeneic hematopoietic stem cell transplantation (allo-HCT). Nevertheless, there is paucity of available data about outcome of this fragile population. We report here the results of a retrospective study designed to evaluate outcome of ALL patients undergoing allo-HCT with KPS score ≤80%. The analysis included ALL patients aged ≥18 years, undergoing allo-HCT in first remission between 2000 and 2018, with a KPS score of 50% to 80% at the time of transplant. Patients who received manipulated grafts or had incomplete data about cytogenetics were excluded. Conditioning intensity was defined according to EBMT definitions (Aoudjhane M. et al, Leukemia 2005; 19: pp. 2304-2312). A total of 1,010 patients were identified. Median age at transplant was 43 years (18-76 years). Median year of transplant was 2011. The KPS score was =80% in 83% of the patients and <80% in 17% of the patients. Diagnosis was Philadelphia chromosome (Ph) negative B-ALL, Ph positive B-ALL or T-ALL in 34%, 44% and 22% of the patients, respectively. Donor type was MSD or 10/10 UD in 60% and 40% of the patients, respectively. Conditioning was myeloablative (MAC) or reduced-intensity (RIC) in 78% and 22% of the patients, respectively, and it was TBI-based in 79% of the patients. Stem cell source was PBSC in 76% and BM in 24% of the patients, respectively. Anti-thymocyte globulin (ATG) was administered to 21% of the patients receiving MSD and 68% of the patients receiving 10/10 UD as donor type. Cumulative incidence of grade II-IV and III-IV aGVHD was 32% and 9%, respectively. The 2-year cumulative incidence of chronic GVHD (cGvHD) and severe cGVHD was 43% and 18%, respectively. Non relapse mortality (NRM) and relapse incidence (RI) at 2 years were 18% and 28%, respectively. At 2 years, leukemia-free survival (LFS), overall survival (OS) and GVHD-free, relapse-free survival (GRFS) rates were 54%, 64% and 41%, respectively. On multivariate analysis, transplant from 10/10 UD was associated with higher incidence of aGVHD (HR 1.8, p<0.0001) and higher risk of NRM (HR 1.7, p<0.01) as compared to MSD. RIC conditioning was associated with higher risk of relapse (HR 1.2, p=0.02), lower LFS (HR 1.3, p=0.03) and lower GRFS (HR 1.3 p=0.02) as compared to MAC. NRM was not significantly different between MAC and RIC. Factors independently associated with improved OS were younger age at transplant, female sex, more recent year of transplant and Ph+ B ALL phenotype. Administration of ATG was associated with reduced risk of developing grade II-IV aGVHD (HR 0.6, p<0.001), cGVHD (HR 0.5, p<10-4) and severe cGVHD (HR 0.4, p<10-4). In conclusion, allo-HCT is feasible in patients with acute lymphoblastic leukemia in first remission and KPS score ≤80%, with acceptable NRM and survival rates. Transplant from a sibling donor was associated with reduced risk of NRM and aGVHD as compared to matched unrelated donor. Interestingly, despite the poor KPS score of the patients included in the analysis, a MAC protocol was associated with similar NRM, lower relapse and better LFS and GRFS as compared to RIC in the selected population. Finally, administration of ATG was associated with reduced acute and chronic GVHD rates. Disclosures Labopin: Jazz Pharmaceuticals: Honoraria. Socie:Alexion: Consultancy. Kröger:JAZZ: Honoraria; Medac: Honoraria; Neovii: Honoraria, Research Funding; Novartis: Honoraria, Research Funding; Riemser: Research Funding; Sanofi-Aventis: Research Funding; Celgene: Honoraria, Research Funding; DKMS: Research Funding. Mohty:Jazz Pharmaceuticals: Honoraria, Research Funding.

scholarly journals Allogeneic Hematopoietic Stem Cell Transplantation for Acute Myeloid Leukemia Patients in First Complete Remission: Significant Impact of the Interval Between Diagnosis and Transplantation on Different Outcomes

Blood ◽  
2015 ◽  
Vol 126 (23) ◽  
pp. 5517-5517 ◽  
Author(s):  
Stéphanie Ducreux ◽  
Mohamad Sobh ◽  
Stéphane Morisset ◽  
Marie Balsat ◽  
Xavier Thomas ◽  
...  
Keyword(s):  
Board Of Directors ◽  
Median Time ◽  
Myeloid Leukemia ◽  
Conditioning Regimen ◽  
Inclusion Criteria ◽  
Advisory Committees ◽  
Hematopoietic Stem ◽  
First Complete Remission ◽  
Acute Myeloid

Abstract Allogeneic hematopoietic stem cell transplantation (allo-HSCT) is the main therapeutic option for most patients with high risk acute myeloid leukemia (AML). In order to determine whether time between diagnosis and allo-HSCT could have any impact on transplant outcomes, we screened 700 consecutive adult AML patients diagnosed between January 2007 and June 2014 at the Lyon Sud Hospital transplant center. Inclusion criteria were: (1) newly diagnosed AML in patients with age ≤ 65 years, (2) AML classified in the intermediate-2 and unfavorable risk groups according to the Acute Leukemia French Association (3) patients fit for receiving chemotherapy (4) patients candidates for allo-HSCT and in first complete remission (CR1) at transplantation. Two hundred and one patients met the inclusion criteria and were enrolled in the study. Among them, 137 (68%) received allo-HSCT of whom 83 (41%) only received HSCT in CR1 after a median time of 143 days (range: 69-265) from diagnosis. We collected within this interval different delays for donor search, including patients HLA typing and time to unrelated donor identification when a sibling donor was not available. Patients were split into 2 groups based on their time to transplant. An "early transplant group" included 28 (33%) patients transplanted after a median time of 108 days (range: 69-133) after diagnosis. The other 55 (67%) patients transplanted after a median time of 163 days (range: 134-265) were qualified as "late transplant group". Patients and transplantation characteristics according to the timing of transplantation are shown in table 1. After a median follow-up of 16 months (range: 0-60) the 5-year probability of overall survival (OS) and disease-free survival (DFS) for the whole population were respectively, 63.4% and 48.3%. The cumulative incidences of non-relapse mortality (NRM) at 1 and 5 years were constant at 17.5%. The multivariate analysis using proportional hazards modeling showed that conditioning regimen and sex mismatching were independent prognostic factors for DFS, with no significant impact on OS. To evaluate the long term impact of transplantation timing on OS and DFS, we performed a landmark analysis for patients surviving at 1 year post-allo-HSCT. This analysis showed that patients in the early transplant group had a higher probability of OS at 3 and 5 years with 100% survival respectively compared to the late transplantation group with 85.5% and 79.4% respectively (p=0.09); accordingly, we found a significant difference in terms of DFS with 100% probability at 3 and 5 years for the early transplantation group compared to 80% and 56% respectively in the late transplantation group (p=0.02). This difference in terms of OS and PFS was still valid after stratification on the type of conditioning regimen. These results confirm the important impact of allogeneic HSCT timing in high-risk AML patients, early allo-HSCT for patients transplanted in CR1 is associated with a better OS and a very significant benefit in terms of DFS. Further analyses are ongoing including disease monitoring from diagnosis to the last follow-up to identify the potential of transplantation timing on the graft versus leukemia effect. Table 1. Table 1. Disclosures Nicolini: Bristol-Myers Squibb: Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Novartis: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; Ariad Pharmaceuticals: Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau.

scholarly journals Predictors of Outcomes in Adult Patients with Therapy Related Acute Myeloid Leukemia Undergoing Allogeneic Hematopoietic Stem Cell Transplantation - Twenty Year Experience from a Tertiary Care Centre

Blood ◽  
2019 ◽  
Vol 134 (Supplement_1) ◽  
pp. 5737-5737
Author(s):  
RAM V Nampoothiri ◽  
Arjun Law ◽  
Wilson Lam ◽  
Zeyad Al-Shaibani ◽  
David Loach ◽  
...  
Keyword(s):  
Overall Survival ◽  
Myeloid Leukemia ◽  
Performance Status ◽  
Chronic Gvhd ◽  
P Value ◽  
Hematopoietic Stem ◽  
Free Survival ◽  
Gvhd Prophylaxis ◽  
Related Mortality ◽  
Acute Myeloid

Background Therapy related acute myeloid leukemia (t-AML) constitutes a subset of AML that has an increased proportion of high risk cytogenetic and molecular features, poor response to therapy, higher relapse, and decreased overall survival. The incidence ranges from 10-20% across various studies. Allogeneic hematopoietic stem cell transplantation (allo-HSCT) offers a potential cure in t-AML, with disease free survival reported up to 30% at 2 years. Most studies on HSCT in t-AML have limited number of patients and are confounded by the inclusion of patients with secondary AML and therapy related myelodysplastic syndromes (t-MDS). We aim to report our 20-year experience of allo-HSCT in t-AML and identify predictors of survival. Patients and Methods We retrospectively reviewed all cases of t-AML who underwent allo-HSCT at our centre from June 1999 to July 2019. We collected data for demographic characteristics, prior malignancy and treatment, latent period before AML, cytogenetic and molecular characteristics of AML, induction treatment received, transplant details (donor details, conditioning regimens, GVHD prophylaxis) as well as post-transplant complications (transplant related mortality, occurrence and severity of acute and chronic GVHD, CMV and EBV reactivations). Primary outcome evaluated was overall survival and secondary outcomes were relapse rate and relapse free survival (RFS). Cox-proportional hazards regression model was used to identify predictors of survival. Results Fifty-two patients underwent allo-HSCT for t-AML during the study period. 58% were male (n=30). Median age at HSCT was 55.5 years (Range 18-70). Baseline characteristics are summarized in Table 1. Complex cytogenetics were present in 23.2% (n=12) patients, while 11q23 rearrangement (MLL-KMT2A), monosomy 7, monosomy 5, and 17p deletion were present in 15.4% (n = 8), 15.4% (n= 8), 7.7% (n = 4) and 7.7% (n=4) patients respectively. Based on the ELN 2017 risk stratification schema, 13.5% (n=7) patients could be considered favorable risk based on cytogenetic and molecular profiles, 36.5% (n=19) intermediate risk, and 57.7% (n=30) in poor risk category. Performance status prior to transplant was ECOG 0/1 in 71.2% (n=37) patients, and 2 in 28.8% (n=15) patients. Myeloablative conditioning was used in 30.8% (n=16) patients, and reduced intensity conditioning in 69.2% (n=36). GVHD prophylaxis was CyclosporineA(CSA)/Methotrexate in 23.1% (n=12), Alemtuzumab/CSA in 21.2% (n=11), ATG/CSA/PTCy in 28.8% (n=15), and other regimens in 26.9% (n=14) patients. Transplant related mortality (death before day+100) was 21.1% (n=11). Acute and chronic GVHD (any grade) occurred in 61.5% (n = 32) and 28.8% (n=15) patients respectively. Eleven patients (21.2%) relapsed with a median RFS of 8 months (Range 0.17-158). Median OS of the whole cohort was 8.9 months (0.17-158 months). No patient had a relapse of their primary malignancy during follow up. RFS at 12 and 24 months were 46% and 28% while OS at 1 and 2 years was 46% and 30%, respectively. Significant predictors of reduced OS (Figure 1a,b,c) after day+100 of HSCT by Cox-regression were ECOG performance status 2 (Hazard ratio - 6.1; p value 0.003), GVHD prophylaxis with CSA/methotrexate (HR - 4.5; p value 0.01), and haploidentical donor transplantation (HR - 34; p value - 0.002). Cytogenetics were a predictor of OS in univariate analysis but not in multivariate regression analysis. No difference in OS was found between patients who underwent HSCT 2010 or prior versus after 2010. Conclusions Patients with favorable cytogenetic profile, better performance status, and an HLA matched donor may have better outcomes after allo-HSCT in therapy related AML. Patients with unfavorable cytogenetic risk profiles may require more intense therapy or post-transplant maintenance therapy to prevent relapse. Disclosures Michelis: CSL Behring: Other: Financial Support. Mattsson:Gilead: Honoraria; Celgene: Honoraria; Therakos: Honoraria.

Outcomes of Hematopoietic Stem Cell Transplantation for Chronic Lymphocytic Leukemia (CLL)/Small Lymphocytic Lymphoma (SLL).

Blood ◽  
2007 ◽  
Vol 110 (11) ◽  
pp. 3045-3045
Author(s):  
John D. Dickinson ◽  
Fausto Loberiza ◽  
Victoria Whalen ◽  
Philip J. Bierman ◽  
Julie M. Vose ◽  
...  
Keyword(s):  
Stem Cell ◽  
Progression Free Survival ◽  
Hematopoietic Stem ◽  
Allogeneic Hsct ◽  
Stem Cell Source ◽  
One Year ◽  
Autologous Hsct ◽  
Treatment Related Mortality ◽  
Related Mortality

Abstract Considerable advancements have been made in our understanding of the biology and treatment of CLL/SLL. Despite these advances, CLL/SLL essentially remains an incurable illness. Hematopoietic stem cell transplantation (HSCT) has been used in an attempt to improve remission duration and survival. However little high level data exists on outcomes for patients (pts) undergoing HSCT for CLL/SLL. We evaluated the long-term survival of 65 CLL/SLL pts who underwent allogeneic or autologous HSCT from 1995 until 2006 at the University of Nebraska Medical Center. The median duration of follow-up for surviving pts is 8.8 years. The median age was 49 years and there was no significant difference in age between the autologous and allogeneic groups. Thirty nine pts underwent allogeneic HSCT (n=25 matched related donor, n=14 matched unrelated donor) and 26 pts underwent autologous HSCT. For the group undergoing allogeneic HSCT, the stem cell source was mobilized peripheral blood progenitor cells in 74% and bone marrow in 26%. In the autologous HSCT group, 81% of pts received peripheral blood and 19% received bone marrow as their stem cell source. In the autologous group there were 19 deaths (10 from progression) over the period of follow-up. In the allogeneic group there were 29 deaths (including 8 from acute regimen related toxicity, 9 from infection, 3 from complications of GVHD, 1 from late pulmonary toxicity, one from PTLD, one from MDS/AML) and 10 pts are alive at end of follow-up. One hundred day mortality was significantly higher in the allogeneic group (20% vs. 6%; p=0.05). For the allogeneic group the cumulative incidence of grade II-IV acute graft versus host disease (GHVD) was 64% (95% confidence interval [CI]=47–76) and the cumulative incidence of chronic extensive GHVD was 50% (95% CI=29–68). One-year progression free survival (PFS) was significantly better among autologous SCT when compared to allogeneic HSCT (77% versus 45%; P=0.006), but at 5 years these differences were no longer apparent. Similarly, one-year overall survival (OS) was significantly better for autologous SCT (81% versus 48%; P=0.003) but at 5 years these differences were no longer significant (49% versus 31%; p=0.15). Among all patients undergoing allogeneic HSCT, 5-year PFS was significantly higher for patients with SLL vs. CLL (36% vs. 25%; P=0.04). In addition, 5 year OS was better for pts with SLL compared to CLL (51% vs. 33%, P=0.06). There was no difference in PFS or OS following autologous SCT between patients with a diagnosis of CLL versus SLL. The group of pts undergoing autologous HSCT demonstrates no plateau on the PFS curve, whereas for pts undergoing allogeneic HSCT there is a suggestion of a plateau in PFS at approximately 25%. In conclusion, CLL/SLL patients undergoing allogeneic SCT had a higher incidence of early treatment related mortality, mainly from regimen related toxicity and infection. In a subgroup analysis pts with CLL appear to have an inferior PFS compared with pts with SLL. This difference may be due to a more prominent underlying immune deficiency in CLL patients that leads to a higher probability of treatment related mortality. Pts with CLL/SLL undergoing autologous HSCT had a lower incidence of treatment related mortality, but there is no evidence of a plateau in progression-free survival.

Sign in / Sign up

Export Citation Format

Share Document