Extramedullary disease at diagnosis of <scp>AML</scp> does not influence outcome of patients undergoing allogeneic hematopoietic cell transplant in <scp>CR</scp>1

Bourlon, Christianne; Lipton, Jeffrey H.; Deotare, Uday; Gupta, Vikas; Kim, Dennis Dong Hwan; Kuruvilla, John; Viswabandya, Auro; Thyagu, Santhosh; Messner, Hans A.; Michelis, Fotios V.

doi:10.1111/ejh.12909

Cited by 20 publications

(13 citation statements)

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“…Indeed, CNS seems to be the most common extramedullary involvement site in most clinical studies in ALL patients [7]. Regarding risk factors for EMR, studies of AML patients reported that extramedullary involvement before transplantation had no impact on outcome [20,21], similar to our large study in both AML and ALL. Despite the reportedly higher incidence of EMR in ALL compared with AML [7À10], our study did not confirm this finding.…”

Section: Discussionsupporting

confidence: 85%

Isolated Extramedullary Relapse as a Poor Predictor of Survival after Allogeneic Hematopoietic Cell Transplantation for Acute Leukemia

Sakellari

Gavriilaki

Batsis

et al. 2019

Biology of Blood and Marrow Transplantation

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Limited and conflicting data exist on outcomes of patients with extramedullary relapses (EMRs) after allogeneic hematopoietic cell transplantation (allo-HCT) for acute leukemias. We retrospectively reviewed charts of consecutive allo-HCT recipients who underwent transplantation in our center with the indication of acute leukemia (July 1990 to July 2018). Incidences of isolated EMR (iEMR) and bone marrow relapse (BMR) were calculated using cumulative incidence (CI) analysis, with each and treatment-related mortality considered a competing risk. We studied 554 allo-HCT recipients for 1.8 years (range, .04 to 27.75). Ten-year CI of 10.5% for iEMR was associated only with advanced disease phase at transplantation, whereas 10-year CI of 34.8% for BMR was independently associated with pretransplant disease phase, lines of treatment, and fungal infections. Most iEMR and BMR patients (75% and 81%, respectively) received systemic treatment combined with local radiation for iEMR (26%) and donor lymphocyte infusions (16% and 28%, respectively) when feasible. Extensive chronic graft-versus-host disease (GVHD) was recorded in 47% of iEMR and 48% of BMR patients. Outcomes were poor both in iEMR (10year overall survival [OS], 18.3%) and BMR (10-year OS, 19.1%). Independent predictors of OS were disease phase, type of donor, acute and chronic GVHD, fungal infections, iEMR, and BMR. In a large population with long-term follow-up, incidence of iEMR was relatively high, developed at the late post-transplant period, and was associated only with disease phase at transplantation. Furthermore, iEMR and BMR conferred similarly poor outcomes despite systemic treatment or extensive chronic GVHD.

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Section: Discussionsupporting

confidence: 85%

Isolated Extramedullary Relapse as a Poor Predictor of Survival after Allogeneic Hematopoietic Cell Transplantation for Acute Leukemia

Sakellari

Gavriilaki

Batsis

et al. 2019

Biology of Blood and Marrow Transplantation

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“…A previous study from our center, which looked at 303 consecutive AML transplants in CR1, reported on 39 patients (13%) with evidence of extramedullary AML prior to transplant (of these, 16 patients [5.2%] had CNS‐AML), and there was no effect of extramedullary involvement on survival. This earlier study did not specifically look at the effect of CNS‐AML on transplant outcomes, which is the focus of the current study in a larger and more recent cohort of patients.…”

Section: Discussionmentioning

confidence: 97%

Impact of central nervous system involvement in AML on outcomes after allotransplant and utility of pretransplant cerebrospinal fluid assessment

Prem

Atenafu

Avena

et al. 2019

European J of Haematology

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Central nervous system (CNS) involvement in adults with acute myeloid leukemia (AML) is uncommon (unlike in acute lymphoblastic leukemia), and there is a paucity of literature on its effect on posttransplant outcomes. 1,2 Predisposing factors for CNS involvement in AML (CNS-AML) reported include high serum lactate dehydrogenase (LDH), high white blood cell (WBC) or blast counts at diagnosis, cytogenetic abnormalities (inversion 16, t (8;21), 11q23 abnormalities), molecular aberrations (FLT3-ITD alone or as co-occurrence with NPM1mutations), French-American-British (FAB) subgroup M4 and M5, and age <20 years. 3-6 At our institution, all AML patients who are potential candidates for allogeneic hematopoietic cell transplantation (allo-HCT) undergo lumbar puncture (LP) and cerebrospinal fluid (CSF) cytospin study as part of pretransplant evaluation. The primary objective of this study Abstract Objective: The primary objective was to assess the effect of central nervous system involvement in acute myeloid leukemia (CNS-AML) on outcomes after allogeneic hematopoietic stem cell transplant (allo-HCT). The secondary objective was to assess the utility of pretransplant cerebrospinal fluid (CSF) assessment in AML. Methods:We retrospectively analyzed survival outcomes in 338 adult AML patients (with and without CNS-AML) after allo-HCT. CNS involvement was defined as clinical, pathological, or radiological evidence of CNS involvement any time after diagnosis. Results:The median follow-up in surviving patients was 23.7 months. Twenty-five patients (7.4%) had prior history of CNS disease, with normal CSF pretransplant.Three patients had CSF blasts detected for the first time at pretransplant evaluation (0.88%). The 2-year OS and RFS in groups with and without CNS involvement were not significantly different. Patients with CNS-AML had significantly higher 1-year cumulative incidence of relapse (29.7% vs 16.9%, P = .048). Age more than 65 years and absence of marrow remission at transplant were significant adverse factors for survival.Conclusion: CNS-AML is not an independent risk factor for survival after allo-HCT, but can be associated with higher relapse rates. Pretransplant CSF assessment has low yield in detecting new CNS disease pretransplant in AML. K E Y W O R D Sallogeneic transplant, AML, CNS involvement

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“…Extramedullary involvement (EMI) refers to leukemic cells found in organs or tissue outside the blood or bone marrow. 1 The most common sites of extramedullary disease are skin, bone, and lymph nodes. 2 Although the exact frequency is unknown, EMI has been estimated to occur in 3–8% of adult patients with acute myeloid leukemia (AML), and it can be diagnosed in concomitance, following or antedating the onset of the bone marrow involvement.…”

Section: Introductionmentioning

confidence: 99%

“…On the other hand, others report that EMI is not an independent indicator of a worse prognosis than medullar disease alone. 1 This study retrospectively analyzes the incidence, risk factors, treatment outcomes, and overall prognosis in a cohort of adult patients with AML with EMI.…”

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confidence: 99%

“…Previous retrospective studies have demonstrated superior outcomes using allogeneic or autologous stem cell transplant in EMI. 24 Bourlon et al 1 investigated the impact of EMI at diagnosis on the outcome of 39 patients transplanted for AML in first complete remission; this study concluded that EMI at the diagnosis of AML did not seem to influence outcomes following allo-HSCT performed in first CR. Interestingly Goyal et al found that the presence of extramedullary disease at any time before allo-HSCT did not adversely affect the outcomes, in terms of OS, leukemia-free survival, treatment-related mortality, or risk of relapse, in a large series of 814 EMI patients when compared with a cohort of AML patients without EMI.…”

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confidence: 99%

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Extramedullary Involvement in Acute Myeloid Leukemia. A Single Center Ten Years Experience

Fianchi

Quattrone

Criscuolo

et al. 2021

Mediterr J Hematol Infect Dis

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The incidence, risk factors and prognostic significance of extramedullary involvement (EMI) in adult patients with acute myeloid leukemia have not been established yet. This study analyzed the clinical and biological characteristics, the impact on prognosis and the cumulative incidence of EMI in a monocentric retrospective study. All consecutive adult pts with a diagnosis of AML observed in our institution between January 2010 and December 2017 were included into the analysis.Overall 346 AMLs were analyzed. The incidence of EMI was 11% (38 pts). The involved sites were: skin (66%), CNS (23%), pleura (7%), lymph nodes (5%), peritoneum (2%), spleen (2%), pancreas (2%), breasts (2%) and bones (2%). Most pts (91%) had only one site of EMI, while 9% had multiple sites affected at the same time. Twenty-four (55%) patients showed signs of EMI at presentation, while extramedullary relapse occurred in 9 pts (24%); 5 pts had EMI both at presentation and at relapse.EMI had a significantly higher frequency in pts with monocytic and myelo-monocytic leukemia subtypes (p<0,0001), MLL rearrangements (p=0.001), trisomy 8 (p=0,02) and a specific cytofluorimetry pattern (CD117-, p= 0,03; CD56-/CD117-, p= 0,04; CD56+/CD117-, p= 0,04).An analysis regarding treatment, OS and DFS was performed only on the 28 patients who experienced EMI at the onset of their disease; one EMI patient received best supportive care and was consequently excluded from OS analysis. The other 27 patients were treated with: conventional chemotherapy (21 pts), hypomethylating agent (5 pts) and low dose citarabine (1 pts); 8 pts (28.5%) received an allogeneic stem cell transplantation (allo-HSCT). Complete remission (CR) rate after induction therapy was 22% with a median DFS of 7.4 months. Median OS of all 27 EMI pts was 11.6 months (range 2-79); this resulted significantly longer for the 8 EMI pts who undergone allo-HSCT than those (19 pts) who didn’t receive this procedure (16.7 vs 8.2 months respectively, p=0.02). Univariate and multivariate analyses showed that undergoing allo-HSCT and achieving CR were the main positive prognostic factors for survival in our population (p<0,0001).This study confirms poor prognosis for EMI pts. Allo-HSCT, applicable however only in some cases, seems to have a crucial role in the therapeutic approach of these patients, being associated with a better prognosis.

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Extramedullary disease at diagnosis of AML does not influence outcome of patients undergoing allogeneic hematopoietic cell transplant in CR1

Abstract: We conclude that EMD at diagnosis of AML does not seem to influence outcomes following allo-HCT performed in CR1.

Cited by 20 publications

References 19 publications

Isolated Extramedullary Relapse as a Poor Predictor of Survival after Allogeneic Hematopoietic Cell Transplantation for Acute Leukemia

Isolated Extramedullary Relapse as a Poor Predictor of Survival after Allogeneic Hematopoietic Cell Transplantation for Acute Leukemia

Impact of central nervous system involvement in AML on outcomes after allotransplant and utility of pretransplant cerebrospinal fluid assessment

Extramedullary Involvement in Acute Myeloid Leukemia. A Single Center Ten Years Experience

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