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Risk stratification using FLT3 and NPM1 in acute myeloid leukemia patients autografted in first complete remission
Shouval, R., Labopin, M., Bomze, D., Baerlocher, G. M., Capria, S., Blaise, D., Hanel, M., Forcade, E., Huynh, A., Saccardi, R., et al
Bone marrow transplantation. 2020
Abstract
FLT3-ITD and NPM1 mutation refine prognostic stratification in acute myeloid leukemia (AML) with intermediate-risk cytogenetics. However, data on their role in patients undergoing autologous stem cell transplantation (Auto-SCT) as post-remission therapy (PRT) are limited. We therefore sought to retrospectively evaluate the role of FLT3-ITD and NPM1 in a cohort of AML patients (n = 405) with intermediate-risk cytogenetics, autografted in first complete remission (CR1). Patients were transplanted between 2000 and 2014 and reported to the European Society for Blood and Marrow Transplantation (EBMT) registry. Leukemia-free survival (LFS) was the primary outcome. Median follow-up was 5.5 years. FLT3-ITD(neg)/NPM1(WT) was the leading molecular subtype (50%), followed by FLT3-ITD(neg)/NPM1(mut) (30%). In the univariate analysis, molecular subtype was associated with LFS, overall survival (OS), and relapse incidence (RI) (p < 0.001); 5-year LFS: FLT3-ITD(neg)/NPM1(mut) 62%, FLT3-ITD(pos)/NPM1(mut) 38%, FLT3-ITD(neg)/NPM1(WT) 32%, and FLT3-ITD(pos)/NPM1(WT) 21%. At 5 years, OS and RI in the FLT3-ITD(neg)/NPM1(mut) subtype were 74% and 35%, respectively. The corresponding OS and RI in other subtypes were below 48% and over 57%. In a Cox multivariable model, molecular subtype was the strongest predictor of LFS, OS, and relapse. In conclusion, AML patients with intermediate-risk cytogenetics and FLT3-ITD(neg)/NPM1(mut) experience favorable outcomes when autografted in CR1, suggesting that Auto-SCT is a valid PRT option.
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Measurable residual disease at myeloablative allogeneic transplantation in adults with acute lymphoblastic leukemia: a retrospective registry study on 2780 patients from the acute leukemia working party of the EBMT
Pavlu, J., Labopin, M., Niittyvuopio, R., Socie, G., Yakoub-Agha, I., Wu, D., Remenyi, P., Passweg, J., Beelen, D. W., Aljurf, M., et al
Journal of hematology & oncology. 2019;12(1):108
Abstract
BACKGROUND Assessment of measurable residual disease (MRD) is rapidly transforming the therapeutic and prognostic landscape of a wide range of hematological malignancies. Its prognostic value in acute lymphoblastic leukemia (ALL) has been established and MRD measured at the end of induction is increasingly used to guide further therapy. Although MRD detectable immediately before allogeneic hematopoietic cell transplantation (HCT) is known to be associated with poor outcomes, it is unclear if or to what extent this differs with different types of conditioning. METHODS In this retrospective registry study, we explored whether measurable residual disease (MRD) before allogeneic hematopoietic cell transplantation (HCT) for acute lymphoblastic leukemia is associated with different outcomes in recipients of myeloablative total body irradiation (TBI)-based versus chemotherapy-based conditioning. We analyzed outcomes of 2780 patients (median age 38 years, range 18-72) who underwent first HCT in complete remission between 2000 and 2017 using sibling or unrelated donors. RESULTS In 1816 of patients, no disease was detectable, and in 964 patients, MRD was positive. Conditioning was TBI-based in 2122 (76%) transplants. In the whole cohort MRD positivity was a significant independent factor for lower overall survival (OS) and leukemia-free survival (LFS), and for higher relapse incidence (RI), with respective hazard ratios (HR, 95% confidence intervals) of 1.19 (1.02-1.39), 1.26 (1.1-1.44), and 1.51 (1.26-1.8). TBI was associated with a higher OS, LFS, and lower RI with HR of 0.75 (0.62-0.90), 0.70 (0.60-0.82), and 0.60 (0.49-0.74), respectively. No significant interaction was found between MRD status and conditioning. When investigating the impact of MRD separately in the TBI and chemotherapy-based conditioning cohorts by multivariate analysis, we found MRD positivity to be associated with lower OS and LFS and higher RI in the TBI group, and with higher RI in the chemotherapy group. TBI-based conditioning was associated with improved outcomes in both MRD-negative and MRD-positive patients. CONCLUSIONS In this large study, we confirmed that patients who are MRD-negative prior to HCT achieve superior outcomes. This is particularly apparent if TBI conditioning is used. All patients with ALL irrespective of MRD status benefit from TBI-based conditioning in the myeloablative setting.
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EBMT prospective observational study on allogeneic hematopoietic stem cell transplantation in T-prolymphocytic leukemia (T-PLL)
Wiktor-Jedrzejczak, W., Drozd-Sokolowska, J., Eikema, D. J., Hoek, J., Potter, M., Wulf, G., Sellner, L., Ljungman, P., Chevallier, P., Volin, L., et al
Bone marrow transplantation. 2019
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Editor's Choice
Abstract
Preliminary data suggest that allogeneic stem cell transplantation (allo-SCT) may be effective in T-prolymphocytic leukemia (T-PLL). The purpose of the present observational study was to assess the outcome of allo-SCT in patients aged 65 years or younger with a centrally confirmed diagnosis of T-PLL. Patients were consecutively registered with the EBMT at the time of transplantation and followed by routine EBMT monitoring but with an extended dataset. Between 2007 and 2012, 37 evaluable patients (median age 56 years) were accrued. Pre-treatment contained alemtuzumab in 95% of patients. Sixty-two percent were in complete remission (CR) at the time of allo-SCT. Conditioning contained total body irradiation with 6 Gy or more (TBI6) in 30% of patients. With a median follow-up of 50 months, the 4-year non-relapse mortality, relapse incidence, progression-free (PFS) and overall survival were 32, 38, 30 and 42%, respectively. By univariate analysis, TBI6 in the conditioning was the only significant predictor for a low relapse risk, and an interval between diagnosis and allo-SCT of more than 12 months was associated with a lower NRM. This study confirms for the first time prospectively that allo-SCT can provide long-term disease control in a sizable albeit limited proportion of patients with T-PLL.
PICO Summary
Population
Allo-SCT in patients aged 65 years or younger with a centrally confirmed diagnosis of T-PLL.
Intervention
Observational study
Comparison
None
Outcome
With a median follow-up of 50 months, the 4-year non-relapse mortality was 32%, relapse incidence 38%, progression-free (PFS) 30% and overall survival 42%. By univariate analysis, TBI6 in the conditioning was the only significant predictor for a low relapse risk, and an interval between diagnosis and allo-SCT of more than 12 months was associated with a lower NRM.
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[The role of autologous hemopoietic stem cell transplantation in T-cell lymphoma. Hungarian data]. [Hungarian]
Szomor, A., Csalodi, R., Kosztolanyi, S., Nagy, A., Pammer, J., Toth, O., Losonczy, H., Alizadeh, H., Miltenyi, Z., Remenyi, P., et al
Orvosi Hetilap. 2017;158(41):1615-1619
Abstract
T-cell lymphoma is a poor prognostic hematological malignancy. The generally used - not sufficiently effective - induction chemotherapy should be improved with consolidative autologous hemopoetic stem cell transplantation. The authors describe the role, place and effectiveness of transplantation in this disorder. One hundred thirty three autologous stem cell transplantations were performed in the last 22 years in Hungary. Detailed results are available from the last 6 years. In this period 43 transplantations were carried out in 4 Hungarian centers. Carmustine-etoposide-cytosine arabinoside-melphalan (BEAM) conditioning regimen was used in 95%. The transplantation was done mainly in complete remission (84%), 1 year after transplantation 65% of patients were still in complete remission. Eleven patients died, 82% of them have progressive disease. Brentuximab vedotin has already proved the effectiveness, several other chemoterapeutics, monoclonal antibodies, kinase inhibitors are under investigation. In certain cases allogeneic stem cell transplantation has real indication among therapeutic options. Orv Hetil. 2017; 158(41): 1615-1619.