Tyrosine kinase inhibitors: relapse prophylaxis after allogeneic hematopoietic stem cell transplantation in adults with Philadelphia chromosome-positive acute lymphoblastic leukemia

Афанасьева, К С; Pirogova, Olga V.; Bakin, Evgeny A.; Smirnova, Anna G.; Morozova, Еlena V.; Vlasova, Yu. A.; Barkhatov, Ildar; Gindina, Tatiana; Moiseev, Ivan S.; Bondarenko, Sergey N.

doi:10.18620/ctt-1866-8836-2022-11-3-4-45-59

Cited by 3 publications

(3 citation statements)

References 32 publications

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“…We also found a bene cial effect of prophylactic use of TKIs after allo-HSCT in our test cohort of patients. Moreover, it was described previously, that TKIs prophylaxis improves long-term RFS and alleviates the negative impact of MRD on the outcomes in Ph-positive ALL adult patients [43]. As we demonstrated, the therapy (TKIs1/TKIs2) is the least important variable in this model, which may be due to the fact that a larger proportion of patients (82%) in the study received prophylactic TKIs after allo-HSCT.…”

Section: Discussionsupporting

confidence: 48%

Implication of machine learning for relapse prediction after allogeneic stem cell transplantation in adults with Ph-positive acute lymphoblastic leukemia

Афанасьева

Bakin

Smirnova

et al. 2023

Preprint

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The posttransplant relapse in Ph-positive ALL increases the risk of death. There is an unmet need for instruments to predict the risk of relapse and plan prophylaxis treatments. In this study we analyzed posttransplant data by machine learning algorithms. Seventy-four Ph-positive ALL patients with median age of 30 (range, 18–55) years, who previously underwent allo-HSCT were retrospectively enrolled. Ninety-three percent of patients received prophylactic/preemptive TKIs after allo-HSCT. The values of the BCR::ABL1 level at serial assessments and over variables were collected in specified intervals after allo-HSCT and were used to model relapse risk with several machine learning approaches. GBM proved superior to the other algorithms utilized and provided maximal AUC score of 0.91. BCR::ABL1 level before and after allo-HSCT, prediction moment and chronic GvHD had the highest value in the model. It was shown that after Day + 100 both error rates don’t exceed 22%, while before D + 100 the model fails to make accurate prediction. After day + 100 patients with chronic GVHD, BCR::ABL1 level more than 0.11% post-transplant and current BCR::ABL1 above 0.06% can be classified as high risk group of relapse. At the same time, if the patient had no chronic GVHD after allo-HSCT till the prediction moment, he should be classified to a high risk group already with a BCR::ABL1 level more than 0,05% at any time point. GBM model with posttransplant laboratory values of BCR::ABL1 provides high prediction of relapse in the era of TKIs prophylaxis. Validation of this approach is warranted.

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Section: Discussionsupporting

confidence: 48%

Implication of machine learning for relapse prediction after allogeneic stem cell transplantation in adults with Ph-positive acute lymphoblastic leukemia

Афанасьева

Bakin

Smirnova

et al. 2023

Preprint

View full text Add to dashboard Cite

show abstract

“…We also found a beneficial effect of prophylactic use of TKIs after allo-HSCT in our test cohort of patients. Moreover, it was described previously that TKIs prophylaxis improves long-term RFS and alleviates the negative impact of MRD on the outcomes in Ph-positive ALL adult patients 43 . As we demonstrated, the therapy (TKIs1/TKIs2) is the least important variable in this model, which may be because more significant proportion of patients (82%) in the study received prophylactic TKIs after allo-HSCT.…”

Section: Discussionmentioning

confidence: 90%

A pilot study of implication of machine learning for relapse prediction after allogeneic stem cell transplantation in adults with Ph-positive acute lymphoblastic leukemia

Afanaseva,

Bakin,

Smirnova

et al. 2023

Sci Rep

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The posttransplant relapse in Ph-positive ALL increases the risk of death. There is an unmet need for instruments to predict the risk of relapse and plan prophylaxis. In this study, we analyzed posttransplant data by machine learning algorithms. Seventy-four Ph-positive ALL patients with a median age of 30 (range 18–55) years who previously underwent allo-HSCT, were retrospectively enrolled. Ninety-three percent of patients received prophylactic/preemptive TKIs after allo-HSCT. The values of the BCR::ABL1 level at serial assessments and over variables were collected in specified intervals after allo-HSCT. They were used to model relapse risk with several machine-learning approaches. GBM proved superior to the other algorithms and provided a maximal AUC score of 0.91. BCR::ABL1 level before and after allo-HSCT, prediction moment, and chronic GvHD had the highest value in the model. It was shown that after Day + 100, both error rates do not exceed 22%, while before D + 100, the model fails to make accurate predictions. As a result, we determined BCR::ABL1 levels at which the relapse risk remains low. Thus, the current BCR::ABL1 level less than 0.06% in patients with chronic GvHD predicts low risk of relapse. At the same time, patients without chronic GVHD after allo-HSCT should be classified as high risk with any level of BCR::ABL1. GBM model with posttransplant laboratory values of BCR::ABL1 provides a high prediction of relapse after allo-HSCT in the era of TKIs prophylaxis. Validation of this approach is warranted.

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“…Также в данной работе продемонстрированы данные об отсутствии негативного влияния положительного статуса МОБ до алло-ТГСК для пациентов в первой полной ремиссии на результаты ОВ и БРВ в отличие от опубликованных ранее исследований [28][29][30], что объясняется вкладом профилактического назначения ИТК после алло-ТГСК в нашей группе (53 пациента (72 %) в группе алло-ТГСК), которые способны обеспечивать длительный контроль над заболеванием после алло-ТГСК и нивелировать негативное влияние положительного статуса МОБ [31].…”

Section: Characteristics Of Patientsunclassified

Place of Allogeneic Hematopoietic Stem Cell Transplantation in the First Complete Remission in Ph-positive Acute Lymphoblastic Leukemia in Adults

Afanaseva,

Smirnova,

Vlasova

et al. 2023

The Scientific Notes of the Pavlov university

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Introduction. Ph-positive acute lymphoblastic leukemia (ALL) is a high risk group of B-lineage acute lymphoblastic leukemia (B-ALL). Since tyrosine kinase inhibitors (TKIs) were introduced, controversial data have been obtained on the efficacy of allogeneic hematopoietic stem cell (allo-HSCT) in the first complete remission.The objective was to evaluate the efficacy of allo-HSCT in the first complete remission of Ph-positive ALL in adult patients after remission induction with continuous chemotherapeutic exposure in combination with TKIs.Methods and materials. The retrospective analysis included 74 patients with a median age of 32 years (range 18–59) after allo-HSCT in the first complete remission and 58 patients with a median age of 39 years (range 18–65) in the first complete remission after conservative therapy. Ninety-one per cent and 83 % of patients received imatinib as TKIs in remission induction in the allo-HSCT and conservative therapy groups, respectively. The median time from the first complete remission to allo-HSCT was 7 months (range 2–33). Thirty-six patients (49 %) had positive minimal residual disease (MRD) status prior to allo-HSCT. Eighteen patients (14 %) over 40 years underwent allo-HSCT in the first complete remission.Results. Allo-HSCT improves overall survival (OS) and relapse-free survival (RFS) and by 9 months since the achievement of the first complete remission, they were 70.1 (95 % CI 56.4–88.6) in the allo-HSCT group versus 45.1 (95 % CI 33.4–61.0) in the conservative group, p=0.025 and 63.3 % (95 % CI 47.6–84.1) in the allo-HSCT group versus 44.8 % (95 % CI 33.2–60.4) in the conservative therapy group, p=0.04, respectively. Allo-HSCT in patients over 40 years does not improve 5-year OS and RFS and were 57.2 % (95 % CI 30.0–84.4) versus 59.8 % (95 % CI 36.9– 82.7), p=0.69, and 42.6 % (95 % CI 14.0–71.2) vs. 50.9 % (95 % CI 29.5–72.3), p=0, 88, respectively.Conclusion. Allo-HSCT performed before 9 months from achievement of the first complete remission after induction with imatinib is the preferred method of remission consolidation in patients from 18 to 40 years old. The optimal therapy for patients older than 40 years in the first complete remission is a conservative approach in combination with TKIs.

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Tyrosine kinase inhibitors: relapse prophylaxis after allogeneic hematopoietic stem cell transplantation in adults with Philadelphia chromosome-positive acute lymphoblastic leukemia

Cited by 3 publications

References 32 publications

Implication of machine learning for relapse prediction after allogeneic stem cell transplantation in adults with Ph-positive acute lymphoblastic leukemia

Implication of machine learning for relapse prediction after allogeneic stem cell transplantation in adults with Ph-positive acute lymphoblastic leukemia

A pilot study of implication of machine learning for relapse prediction after allogeneic stem cell transplantation in adults with Ph-positive acute lymphoblastic leukemia

Place of Allogeneic Hematopoietic Stem Cell Transplantation in the First Complete Remission in Ph-positive Acute Lymphoblastic Leukemia in Adults

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