Impact of Allogeneic Stem Cell Transplantation in First Complete Remission in Acute Myeloid Leukemia: A National Population-Based Cohort Study

Østgård, Lene Sofie Granfeldt; Lund, Jennifer L.; Nørgaard, Jan Maxwell; Nørgaard, Mette; Medeiros, Bruno C.; Nielsen, Bendt; Nielsen, Ove Juul; Overgaard, Ulrik Malthe; Kallenbach, Maria; Marcher, Claus Werenberg; Riis, Anders H.; Sengeløv, Henrik

doi:10.1016/j.bbmt.2017.10.019

Cited by 24 publications

(22 citation statements)

References 47 publications

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“…HCT is a potentially curable treatment primarily used as post-remission therapy in younger patients in the intermediate or adverse risk groups [23,143,144], but is also an option in relapsed or refractory AML [145,146]. Genetic risk, age, comorbidities, treatment response and availability of a donor form the basis of transplant decisions [3,22].…”

Section: Allogeneic Stem Cell Transplantationmentioning

confidence: 99%

Secondary Acute Myeloid Leukemia and the Role of Allogeneic Stem Cell Transplantation in a Population-Based Setting

Nilsson

Hulegårdh

Garelius

et al. 2019

Biology of Blood and Marrow Transplantation

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Secondary acute myeloid leukemia (s-AML) refers to patients with either therapy-related AML (t-AML), that is, AML after treatment with chemo-and/or radiation for a prior disease, or AML progressing from an antecedent hematologic disorder (AHD-AML), typically a myelodysplastic syndrome (MDS) or a myeloproliferative neoplasm. Patients with s-AML present with higher rates of adverse cytogenetic aberrations and higher frequencies of adverse mutations and, subsequently, respond worse to therapy, and have poorer outcome compared to de novo AML. To identify clinical and molecular factors that may improve prognostication is therefore of importance to guide clinical decision-making. The general aim of this thesis was to broaden the real-world knowledge of s-AML, regarding disease properties and outcome, using population-based registries, and additionally to investigate the importance of mutations in the transformation from MDS to AML. The research papers presented herein cover mutational screening in MDS and s-AML (study I), general characteristics and outcome of s-AML (study II), the role of allogeneic hematopoietic cell transplantation (HCT) in patients with s-AML (study III), and the epidemiology and treatment outcome specifically for t-AML (study IV). långtidsöverlevare utan transplantation. Att genomgå transplantation i s.k. första remission var överlägset behandling med enbart cytostatika. Studie IV fokuserade på patienter med terapirelaterad AML. Data från svenska AMLregistret på 686 patienter kombinerades med data från Socialstyrelsens cancerregister och Svensk Reumatologis Kvalitetsregister. Huvudsakliga fynd var att incidensen av t-AML tydligt ökar över tid och att andelen terapirelaterad AML av AML-fallen totalt blev allt större. Överlevnaden vid terapirelaterad AML var generellt mycket dyster, men i vissa genetiska undergrupper var den bättre och jämförbar med patienter med motsvarande genetisk riskprofil som nyinsjuknat i AML. Sammanfattningsvis är sekundär-AML en ovanlig sjukdom som är mycket svårbehandlad. Nya läkemedel kommer att krävas för att förbättra överlevnaden, men förhoppningsvis kommer sådana att utvecklas hand i hand med den ökade förståelsen av sjukdomsbiologin. Behandlingen av AML har i stort sett varit oförändrad i årtionden, men nyligen har läkemedel som bl.a. utnyttjar specifika genetiska avvikelser introducerats. Inom andra cancerformer har immun-och cellterapi fått stort genomslag och dessa är potentiellt användbara även mot AML. För gruppen med sekundär-AML är det därför av stor betydelse att sjukdomshistorik, hög ålder och samsjuklighet inte utgör hinder för deltagande i kommande läkemedelsstudier. LIST OF SCIENTIFIC PAPERS I. High-throughput mutational screening adds clinically important information in myelodysplastic syndromes and secondary or therapy-related acute myeloid leukemia.

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Section: Allogeneic Stem Cell Transplantationmentioning

confidence: 99%

Secondary Acute Myeloid Leukemia and the Role of Allogeneic Stem Cell Transplantation in a Population-Based Setting

Nilsson

Hulegårdh

Garelius

et al. 2019

Biology of Blood and Marrow Transplantation

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“…The median age of patients diagnosed with acute myeloid leukemia (AML) is 68 years, and more than 30% of patients with AML are over 75 years . Retrospective and registry studies suggest that allogeneic hematopoietic cell transplantation (HCT) offers the best chance of durable remissions compared to non‐transplant strategies, even in older adults . For many patients with AML, including those with high risk genetic features, HCT is the only potentially curative option.…”

Section: Introductionmentioning

confidence: 99%

Phase I/II multisite trial of optimally dosed clofarabine and low‐dose TBI for hematopoietic cell transplantation in acute myeloid leukemia

et al. 2019

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Clofarabine is an immunosuppressive purine nucleoside analog that may have better anti-leukemic activity than fludarabine. We performed a prospective phase I/II multisite trial of clofarabine with 2 Gy total body irradiation as non-myeloablative conditioning for allogeneic hematopoietic cell transplantation in adults with acute myeloid leukemia who were unfit for more intense regimens. Our main objective was to improve the 6-month relapse rate following non-myeloablative conditioning, while maintaining historic rates of non-relapse mortality (NRM) and engraftment.Forty-four patients, 53 to 74 (median: 69) years, were treated with clofarabine at 150 to 250 mg/m 2 , of whom 36 were treated at the maximum protocol-specified dose. One patient developed multifactorial acute kidney injury and another developed multiorgan failure, but no other grade 3 to 5 non-hematologic toxicities were observed. All patients fully engrafted. The 6-month relapse rate was 16% (95% CI, 5%-27%) among all patients and 14% (95% CI, 3%-26%) among high-risk patients treated at the maximum dose, meeting the pre-specified primary efficacy endpoint.Overall survival was 55% (95% CI, 40%-70%) and leukemia-free survival was 52% (95% CI, 37%-67%) at 2 years. Compared to a historical high-risk cohort treated with the combination of fludarabine at 90 mg/m 2 and 2 Gy TBI, protocol patients treated with the clofarabine-TBI regimen had lower rates of overall mortality (HR of 0.50, 95% CI, 0.28-0.91), disease progression or death (HR 0.48, 95% CI, 0.27-0.85), and morphologic relapse (HR 0.30, 95% CI, 0.13-0.69), and comparable NRM (HR 0.85, 95% CI 0.36-2.00). The combination of clofarabine with TBI warrants further investigation in patients with high-risk AML.

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“…Many centers now pursue allogeneic HCT in fit individuals who are older, providing transplant options to a much greater number of patients [3,4]. Both acute myeloid leukemia and acute lymphoblastic leukemia have poor prognosis in older patients [5], making transplant the preferred option to improve patient chances of cure [3].…”

Section: Introductionmentioning

confidence: 99%

Effect of Donor Age and Donor Relatedness on Time to Allogeneic Hematopoietic Cell Transplantation in Acute Leukemia

Visram

Aziz

Bryant

et al. 2018

Biology of Blood and Marrow Transplantation

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Relapse after allogeneic hematopoietic cell transplantation (HCT) for acute leukemia can be reduced when pursued early after first complete remission. The impact of donor age and donor relatedness on the time from diagnosis to transplant in patients with acute leukemia was examined to clarify the design of future prospective studies that can address optimal donor choice. Files of 100 consecutive patients undergoing transplantation for leukemia were reviewed. Recipients of related donors (RDs) and unrelated donors (UDs) were not significantly different in terms of recipient gender, age, underlying diagnosis, disease risk index, graft source, or donor HLA match. UDs were significantly younger than RDs (median age, 29 versus 51, P < .001). Multivariate linear regression revealed that when controlling for age of donor and recipient, the time from diagnosis to transplant was 35% longer with UDs compared with RDs (P = .018). No significant correlation was observed between donor and recipient age on length of time to transplant (P = .134 and P = .850, respectively), when controlling for other variables. The steps in UD procurement that contribute most to the longer time to transplant relate to activating the donor workup and scheduling the donor workup before cell collection. Understanding sources of delay in the transplant process will help transplant centers and UD registries reduce the time to transplant for patients with acute leukemia and will provide necessary insight for the design of prospective controlled studies that can address optimal donor choice.

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Impact of Allogeneic Stem Cell Transplantation in First Complete Remission in Acute Myeloid Leukemia: A National Population-Based Cohort Study

Cited by 24 publications

References 47 publications

Secondary Acute Myeloid Leukemia and the Role of Allogeneic Stem Cell Transplantation in a Population-Based Setting

Secondary Acute Myeloid Leukemia and the Role of Allogeneic Stem Cell Transplantation in a Population-Based Setting

Phase I/II multisite trial of optimally dosed clofarabine and low‐dose TBI for hematopoietic cell transplantation in acute myeloid leukemia

Effect of Donor Age and Donor Relatedness on Time to Allogeneic Hematopoietic Cell Transplantation in Acute Leukemia

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