Publications by authors named "Alexander Karachunskiy"

6 Publications

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Prognostic value of minimal residual disease measured by fusion-gene transcript in infants with KMT2A-rearranged acute lymphoblastic leukaemia treated according to the MLL-Baby protocol.

Br J Haematol 2021 Jun 14;193(6):1151-1156. Epub 2021 Feb 14.

Regional Children's Hospital, Ekaterinburg, Russian Federation.

The prognostic value of minimal residual disease (MRD) measured by fusion-gene transcript (FGT) detection was investigated in 76 infants (aged ≤1 year) with acute lymphoblastic leukaemia (ALL) with lysine methyltransferase 2A (KMT2A) rearrangements. Either at the end of induction or at later time-points, FGT-MRD-positivity was associated with poor outcome. FGT-MRD-positivity after first consolidation or first high-risk block detected 46·5% of infants with extremely poor outcome [disease-free survival (SE) 0·06 (0·06), cumulative incidence of relapse (SE) 0·91 (0·05)], which was also confirmed in multivariable analysis. Thus, FGT-MRD measurement at a single time-point clearly identifies infants with ALL who are curable with conventional chemotherapy and those who would benefit only from other treatment approaches.
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June 2021

Reduced vs. standard dose native E. coli-asparaginase therapy in childhood acute lymphoblastic leukemia: long-term results of the randomized trial Moscow-Berlin 2002.

J Cancer Res Clin Oncol 2019 Apr 6;145(4):1001-1012. Epub 2019 Mar 6.

Department of Pediatric Oncology/Hematology, Regional Oncological Hospital, Orenburg, Russia.

Purpose: Favorable outcomes were achieved for children with acute lymphoblastic leukemia (ALL) with the first Russian multicenter trial Moscow-Berlin (ALL-MB) 91. One major component of this regimen included a total of 18 doses of weekly intramuscular (IM) native Escherichia coli-derived asparaginase (E. coli-ASP) at 10000 U/m during three consolidation courses. ASP was initially available from Latvia, but had to be purchased from abroad at substantial costs after the collapse of Soviet Union. Therefore, the subsequent trial ALL-MB 2002 aimed at limiting costs to a reasonable extent and also at reducing toxicity by lowering the dose for standard risk (SR-) patients to 5000 U/m without jeopardizing efficacy.

Methods: Between April 2002 and November 2006, 774 SR patients were registered in 34 centers across Russia and Belarus, 688 of whom were randomized. In arm ASP-5000 (n = 334), patients received 5000 U/m and in arm ASP-10000 (n = 354) 10 000 U/m IM.

Results: Probabilities of disease-free survival, overall survival and cumulative incidence of relapse at 10 years were comparable: 79 ± 2%, 86 ± 2% and 17.4 ± 2.1% (ASP-5000) vs. 75 ± 2% and 82 ± 2%, and 17.9 ± 2.0% (ASP-10000), while death in complete remission was significantly lower in arm ASP-5000 (2.7% vs. 6.5%; p = 0.029).

Conclusion: Our findings suggest that weekly 5000 U/mE. coli-ASP IM during consolidation therapy are equally effective, more cost-efficient and less toxic than 10000 U/m for SR patients with childhood ALL.
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April 2019

Absolute count of leukemic blasts in cerebrospinal fluid as detected by flow cytometry is a relevant prognostic factor in children with acute lymphoblastic leukemia.

J Cancer Res Clin Oncol 2019 May 6;145(5):1331-1339. Epub 2019 Mar 6.

Regional Children Hospital, 32, S. Deryabina Str., 620149, Ekaterinburg, Russian Federation.

Background: Usually, central nervous system (CNS) involvement in acute lymphoblastic leukemia (ALL) is diagnosed by cytomorphology (CM) of cerebrospinal fluid (CSF) on cytospin slides. Multicolor flow cytometry (MFC) provides the opportunity to detect low numbers of leukemia cells undetectable by CM. The present study aimed at evaluating the clinical significance of MFC for the diagnosis of CNS involvement at initial manifestation of childhood ALL.

Methods: In 155 children with ALL, CSF samples were studied in parallel by CM and MFC. Patients were treated according to protocol ALL-MB-2008 for childhood ALL. The prognostic impact of the leukemia burden in CSF was determined categorizing the findings as positive/negative. In addition, the absolute blast cell count per 1 ml of CSF was studied as a continuous variable.

Results: CSF positivity was significantly more frequent using MFC compared with CM (35.3% vs. 15.3% of patients). The outcome of MFC-positive and MFC-negative patients was not different in clinically relevant patient risk groups-CNS1, standard and intermediate-risk groups. Using the quantitative approach, at the threshold level of 20 blasts per ml of CSF, patients could be divided into two groups with a significantly different outcome, irrespective of the clinical risk group, the type of CNS-directed therapy, and the CNS status determined by CM.

Conclusions: Our data do not support the concept of re-stratification and modification of therapy based on qualitative CSF investigation by MFC. However, MFC is a highly sensitive technique of CSF investigation improving the definition of CNS involvement in childhood ALL, and quantitative measurement of blast cells in CSF, if well-organized, can be a useful additional tool for stratification of patients in clinical trials.
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May 2019