Redefining and measuring transplant conditioning intensity in current era: a study in acute myeloid leukemia patients

Spyridonidis, Alexandros; Labopin, Myriam; Savani, Bipin N.; Niittyvuopio, Riitta; Blaise, Didier; Craddock, Charles; Socié, Gèrard; Platzbecker, Uwe; Beelen, Dietrich; Milpied, Noël; Cornelissen, Jan J.; Ganser, Arnold; Huynh, Anne; Griškevičius, Laimonas; Giebel, Sebastian; Aljurf, Mahmoud; Brissot, Éolia; Malard, Florent; Esteve, Jordi; Perić, Zinaida; Baron, Frédéric; Ruggeri, Annalisa; Schmid, Christoph; Gilleece, Maria; Gorin, Norbert Claude; Lanza, Francesco; Shouval, Roni; Versluis, Jurjen; Bug, Gesine; Fløisand, Yngvar; Ciceri, Fabio; Sanz, Jaime; Bazarbachi, Ali; Nagler, Arnon; Mohty, Mohamad

doi:10.1038/s41409-020-0803-y

Cited by 128 publications

(94 citation statements)

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“…Such protocols are believed to be associated with similar anti-leukemic effect but better tolerability as compared to standard protocols as busulfan and cyclophosphamide or cyclophosphamide and total body irradiation, 19 and should be regarded as protocols with intermediate intensity, sharing both MAC and RIC features, as shown by a recent study. 33 Globally, the findings of the present analysis emphasize the strong predictive power of KPS score in AML patients undergoing allo-SCT; furthermore, they shed new light on its impact on clinical practice. First, a reduced performance status should not be considered per-se a major obstacle in performing a transplant in a patient with AML in CR1.…”

Section: Discussionsupporting

confidence: 57%

“…Indeed, a significant proportion of the patients included in our study received modern myeloablative regimens as fludarabine combined with an alkylator at myeloablative dosage, commonly referred to as “reduced toxicity regimens”. Such protocols are believed to be associated with similar anti‐leukemic effect but better tolerability as compared to standard protocols as busulfan and cyclophosphamide or cyclophosphamide and total body irradiation, 19 and should be regarded as protocols with intermediate intensity, sharing both MAC and RIC features, as shown by a recent study 33 …”

Section: Discussionmentioning

confidence: 99%

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Allogeneic stem cell transplant in patients with acute myeloid leukemia and karnofsky performance status score less than or equal to 80%: A study from the acute leukemia working party of the European Society for Blood and Marrow Transplantation (EBMT)

et al. 2020

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Limited data are currently available on the outcome of patients with acute myeloid leukemia (AML) undergoing allogeneic stem cell transplantation (allo‐SCT) with a reduced performance status. We herein present the results of a registry study on 2,936 AML patients undergoing allo‐SCT in first remission (CR1) with a Karnofsky Performance Status (KPS) score less than or equal to 80%. Two‐year leukemia‐free survival (LFS), overall survival (OS) and graft‐versus‐host disease (GVHD)‐free, and relapse‐free survival (GRFS) rates were 54%, 59%, and 41%, respectively. In multivariable analysis, patients with a KPS score = 80% had lower non‐relapse mortality (NRM) and superior OS in comparison to patients with a KPS score <80% (p < 0.001). In the subgroup of patients with a KPS score =80%, a reduced‐intensity conditioning (RIC) regimen was associated with an increased risk of relapse (p = 0.002) and lower GRFS (p < 0.001) compared to myeloablative conditioning (MAC). Differently, in patients with a KPS score <80%, a RIC regimen resulted in lower NRM (p < 0.001), whereas relapse incidence did not differ, thus leading to an improved GRFS (p = 0.008) as compared to MAC. A transplant from a matched sibling donor (MSD) was associated with a reduced incidence of grade III‐IV acute GVHD (p < 0.01) and NRM (p < 0.01) in comparison to other donor types. In conclusion, allo‐SCT appears feasible in AML patients with a jeopardized KPS score. Survival is significantly affected by the conditioning intensity, which should be adjusted according to the severity of KPS impairment.

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Section: Discussionsupporting

confidence: 57%

Section: Discussionmentioning

confidence: 99%

Allogeneic stem cell transplant in patients with acute myeloid leukemia and karnofsky performance status score less than or equal to 80%: A study from the acute leukemia working party of the European Society for Blood and Marrow Transplantation (EBMT)

et al. 2020

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“…The composite endpoint GRFS was defined as survival without the following events: stage III–IV aGVHD, severe cGVHD, disease relapse, or death from any cause after SCT [ 14 ]. Myeloablative conditioning (MAC) was defined as a regimen containing either total body irradiation (TBI) with a dose > 6 Gray, a total dose of oral busulfan > 8 mg/kg, or a total dose of intravenous busulfan > 6.4 mg/kg [ 15 ]. All other regimen intensities were defined as reported by the centers.…”

Section: Methodsmentioning

confidence: 99%

Post-transplant cyclophosphamide containing regimens after matched sibling, matched unrelated and haploidentical donor transplants in patients with acute lymphoblastic leukemia in first complete remission, a comparative study of the ALWP of the EBMT

et al. 2021

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Background There is no information on the impact of donor type in allogeneic hematopoietic stem cell transplantation (HCT) using homogeneous graft-versus-host (GVHD) prophylaxis with post-transplant cyclophosphamide (PTCy) in acute lymphoblastic leukemia (ALL). Methods We retrospectively analyzed outcomes of adult patients with ALL in CR1 that had received HCT with PTCy as GVHD prophylaxis from HLA-matched sibling (MSD) (n = 78), matched unrelated (MUD) (n = 94) and haploidentical family (Haplo) (n = 297) donors registered in the EBMT database between 2010 and 2018. The median follow-up period of the entire cohort was 2.2 years. Results Median age of patients was 38 years (range 18–76). Compared to MSD and MUD, Haplo patients received peripheral blood less frequently. For Haplo, MUD, and MSD, the cumulative incidence of 100-day acute GVHD grade II–IV and III–IV, and 2-year chronic and extensive chronic GVHD were 32%, 41%, and 34% (p = 0.4); 13%, 15%, and 15% (p = 0.8); 35%, 50%, and 42% (p = 0.01); and 11%, 17%, and 21% (p = 0.2), respectively. At 2 years, the cumulative incidence of relapse and non-relapse mortality was 20%, 20%, and 28% (p = 0.8); and 21%, 18%, and 21% (p = 0.8) for Haplo, MUD, and MSD, respectively. The leukemia-free survival, overall survival and GVHD-free, relapse-free survival for Haplo, MUD, and MSD was 59%, 62%, and 51% (p = 0.8); 66%, 69%, and 62% (p = 0.8); and 46%, 44%, and 35% (p = 0.9), respectively. On multivariable analysis, transplant outcomes did not differ significantly between donor types. TBI-based conditioning was associated with better LFS. Conclusions Donor type did not significantly affect transplant outcome in patient with ALL receiving SCT with PTCy.

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“…In case of any deviation from a typical clinical course, BM biopsy was scheduled earlier at the discretion of the treating physician. Cytogenetics, remission status prior to transplant, conditioning intensity, and graft-versus-host disease (GvHD) were defined as previously described [ 19 , 20 , 21 , 23 , 24 , 39 ]. Regarding response evaluation after relapse, no complete hematologic recovery was required for definition of complete remission (CR), as cytopenia might be related to other factors than the underlying disease, for example GvHD or viral infections.…”

Section: Methodsmentioning

confidence: 99%

Prediction of Response and Survival Following Treatment with Azacitidine for Relapse of Acute Myeloid Leukemia and Myelodysplastic Syndromes after Allogeneic Hematopoietic Stem Cell Transplantation

Rautenberg

Bergmann

Germing

et al. 2020

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To provide long-term outcome data and predictors for response and survival, we retrospectively analyzed all 151 patients with relapse of myeloid neoplasms after allogeneic hematopoietic stem cell transplantation (allo-HSCT) who were uniformly treated with first-line azacitidine (Aza) salvage therapy at our center. Patients were treated for molecular (39%) or hematologic relapse (61%), with a median of 5 cycles of Aza and at least one donor lymphocyte infusion in 70% of patients. Overall response was 46%, with 41% achieving complete (CR) and 5% achieving partial remission. CR was achieved after a median of 4 cycles and lasted for a median of 11 months (range 0.9 to 120 months). With a median follow-up of 22 months (range: 1 to 122 months), the 2-year survival rate was 38% ± 9%, including 17 patients with ongoing remission for >5 years. Based on results from multivariate analyses, molecular relapse and time to relapse were integrated into a score, clearly dividing patients into 3 subgroups with CR rates of 71%, 39%, and 29%; and 2-year survival rates of 64%, 38%, and 27%, respectively. In the subgroup of MDS and secondary AML, receiving upfront transplantation was associated with superior response and survival, and therefore pretransplant strategy was integrated together with relapse type into a MDS–sAML-specific score. Overall, Aza enables meaningful responses and long-term survival, which is a predictable with a simple-to-use scoring system.

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Redefining and measuring transplant conditioning intensity in current era: a study in acute myeloid leukemia patients

Cited by 128 publications

References 28 publications

Allogeneic stem cell transplant in patients with acute myeloid leukemia and karnofsky performance status score less than or equal to 80%: A study from the acute leukemia working party of the European Society for Blood and Marrow Transplantation (EBMT)

Allogeneic stem cell transplant in patients with acute myeloid leukemia and karnofsky performance status score less than or equal to 80%: A study from the acute leukemia working party of the European Society for Blood and Marrow Transplantation (EBMT)

Post-transplant cyclophosphamide containing regimens after matched sibling, matched unrelated and haploidentical donor transplants in patients with acute lymphoblastic leukemia in first complete remission, a comparative study of the ALWP of the EBMT

Prediction of Response and Survival Following Treatment with Azacitidine for Relapse of Acute Myeloid Leukemia and Myelodysplastic Syndromes after Allogeneic Hematopoietic Stem Cell Transplantation

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