hematopoietic stem cell transplantation

Achievements and Challenges of Evidence-Based Medicine in Hematopoietic Stem Cell Transplantation: An Analysis of Single-Center and Multicenter Trials

AUTOIMMUNE THROMBOCYTOPENIA ,

BV Afanasyev, IS Moiseev, NG Volkov, KV Lepik, NB Mikhailova, SN Bondarenko, LS Zubarovskaya, EV Morozova, OV Paina, PV Kozhokar, ZhZ Rakhmanova, OV Pirogova, KS Afanas’eva, AV Beinarovich, EV Semenova, OG Smykova, IV Markova, TA Bykova, AL Alyanskii, BI Smirnov, MD Vladovskaya, AG Smirnova, NE Ivanova, AD Kulagin

RM Gorbacheva Scientific Research Institute of Pediatric Oncology, Hematology and Transplantation; IP Pavlov First Saint Petersburg State Medical University, 6/8 L’va Tolstogo str., Saint Petersburg, Russian Federation, 197022

For correspondence: Ivan Sergeevich Moiseev, MD, PhD, 6/8 L’va Tolstogo str., Saint Petersburg, Russian Federation, 197022; e-mail: moisiv@mail.ru

For citation: Afanasyev BV, Moiseev IS, Volkov NG, et al. Achievements and Challenges of Evidence-Based Medicine in Hematopoietic Stem Cell Transplantation: An Analysis of Single-Center and Multicenter Trials. Clinical oncohematology. 2020;13(3):260–72. (In Russ).

DOI: 10.21320/2500-2139-2020-13-3-260-272

ABSTRACT

Randomized multicenter trials in the area of hematopoietic stem cell transplantation (HSCT) face considerable challenges, therefore, their amount is relatively small. Most clinical guidelines are based on the data of multicenter registry studies or well-controlled prospective single-center non-randomized studies. To determine the criteria of a well-controlled single-center trial the results of which can be confirmed by a multicenter analysis, the total of 44 groups of patients from 22 cooperative studies in collaboration with EBMT were analyzed. The results of these studies were compared with single-center data and the results of the planned studies of RM Gorbacheva Scientific Research Institute of Pediatric Oncology, Hematology and Transplantation. In 43 % of cases significant differences were observed, whereby result-difference probability did not decrease with a rising number of patients in the single-center groups, but became higher (odds ratio 1.037; 95% confidence interval 1.001–1.074; p = 0.046), which highlights the differences in methods of single- and multicenter trials. While analyzing the reasons of significant results the following necessary criteria for high-quality single-center trials in the area of HSCT were formulated: 1) conditioning regimens and graft-versus-host disease prophylaxis (if they are not subject of the study) need to be consistent with the most frequently used practices; 2) groups of patients should be status-homogeneous; 3) the trial must not include the patients treated more than 5 years before the analysis; 4) patients should receive current antitumor therapy at pre- and post-transplantation stages; 5) each compared group should include more than 30–40 patients.

Keywords: hematopoietic stem cell transplantation, evidence-based medicine, single-center trials, multicenter trials, meta-analysis.

Received: April 1, 2020

Accepted: June 20, 2020

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Supportive (Maintenance) Therapy in Hematopoietic Stem Cell Transplantation: Main Principles and New Perspectives

BONE MARROW TRANSPLANTATION , , , , , ,

VP Pop, OA Rukavitsyn

NN Burdenko Main Military Clinical Hospital, 3 Gospitalnaya sq., Moscow, Russian Federation, 105229

For correspondence: Vasilii Petrovich Pop, PhD, 3 Gospitalnaya sq., Moscow, Russian Federation, 105229; Tel.: +7(903)178-94-12; Fax: 8(499)263-07-39; e-mail: vasiliypop@mail.ru

For citation: Pop VP, Rukavitsyn OA. Supportive (Maintenance) Therapy in Hematopoietic Stem Cell Transplantation: Main Principles and New Perspectives. Clinical oncohematology. 2017;10(4):501–13 (In Russ).

DOI: 10.21320/2500-2139-2017-10-4-501-513

ABSTRACT

Supportive (maintenance) therapy (ST) for hematopoietic stem cell transplantation (HSCT) is undergoing significant changes and development. The aim of the review was to summarise the basic data on methods and perspective of ST for HSCT and to analyse new opportunities and alternative approaches to enhance the antitumor potential of HSCT. The need for ST is constantly growing as a result of significant increase in the number of performed HSCT and an increase in patient survival. The review highlights traditional methods of ST which allowed to boost the success of HSCT: antibacterial, antifungal, and antiviral preventive treatment. The authors discuss preventing toxicity of dimethyl sulfoxide (cryopreserving agent); understudied aspects of vaccination of HSCT recipients, and effects on microbiota. The study demonstrates that many of the classic recommendations of ST are being constantly updated given the wide variability of approaches not only to post-transplant monitoring, but also to empirical antibiotic therapy and the use of hematopoietic growth factors and the appropriateness of the correction of the microbiota, constraints of the external environment and social contacts. Currently, HSCT is becoming more available, in conditions close to the out-patient clinics, which leads to improved outcomes and significantly decreases the cost of hospital stay. The future improvement of the cost effectiveness and quality of ST will be possible due to health information technologies, and digital infrastructure between doctor and patient. We report our own experience of ST for allo-HSCT in 19 patients and for auto-HSCT in 82 patients, and implementation of auto-HSCT in non-insulated wards without HEPA-filtration. The literature review shows both the increased demand for the various methods of ST at HSCT and its increasing efficiency. Despite the lack of uniform standards, introduction of new approaches of ST should significantly improve HSCT outcomes.

Keywords: hematopoietic stem cell transplantation, supportive therapy, mucositis, antibacterial, antifungal and antiviral preventive measures, microbiota, posttransplant complications.

Received: March 26, 2017

Accepted: May 22, 2017

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Effectiveness of Search for Unrelated Donor of Hematopoietic Stem Cells using Russian System Bone Marrow Donor Search: Experience of RM Gorbacheva Scientific Research Institute of Pediatric Hematology and Transplantation

BONE MARROW TRANSPLANTATION , ,

OA Makarenko, AL Alyanskii, NE Ivanova, MA Kucher, EV Babenko, MA Estrina, DE Pevtsov, AA Golovacheva, EV Kuz’mich, BV Afanas’ev

RM Gorbacheva Scientific Research Institute of Pediatric Hematology and Transplantation; Academician IP Pavlov First St. Petersburg State Medical University, 6/8 L’va Tolstogo str., Saint Petersburg, Russian Federation, 197022

For correspondence: Maksim Anatol’evich Kucher, PhD, 12 Rentgena str., Saint Petersburg, Russian Federation, 197022; Tel: +7(812)338-62-60; e-mail: doctorkucher@yandex.ru

For citation: Makarenko OA, Alyanskii AL, Ivanova NE, et al. Effectiveness of Search for Unrelated Donor of Hematopoietic Stem Cells using Russian System Bone Marrow Donor Search: Experience of RM Gorbacheva Scientific Research Institute of Pediatric Hematology and Transplantation. Clinical oncohematology. 2017;10(1):39–44 (In Russ).

DOI: 10.21320/2500-2139-2017-10-1-39-44

ABSTRACT

Background & Aims. The key condition for allogeneic hematopoietic stem cell transplantation (allo-HSCT) is the presence of HLA-compatible related or unrelated donor. If related donor is not found, further search is carried out in the Bone Marrow Donor Worldwide (BMDW) international data base, which is not effective enough (about 80–85 %), because of genotype specificity of Russian Federation residents. The recruitment procedure using BMDW takes a lot of time and is expensive. Therefore, there are good reasons to develop an alternative Russian data base, Bone Marrow Donor Search (BMDS), which includes data from Russian bone marrow donor registries and has a good potential. The aim is to evaluate the effectiveness of hematopoietic stem cell (HSC) donor search and transplant quality using the BMDS search system.

Methods. 34 allo-HSCT recipients with malignancies and hematological diseases were enrolled in the study in RM Gorbacheva Scientific Research Institute of Pediatric Hematology and Transplantation from November, 2012, to March, 2016. A HLA-compatible donor was found for each patient in the BMDS (www.bmds.info), which includes data from 13 Russian registries of HSC donors.

Results. 34 allo-HSCTs were performed from unrelated donors recruited using Russian registries: 1 in 2012; 3 in 2013; 5 in 2014; 21 in 2015; and 4 in the 1st quarter of 2016. The greatest effectiveness of the BMDS search was in 2015 (14 %, n = 17). In 30 cases (88.2 %) a complete 10/10 compatibility for 5 HLA-gene loci was observed; in 4 cases (11.8 %) there was an incomplete compatibility (9/10). AB0 compatibility was only in 7 cases (20.6 %). In 15 cases (44.1 %) bone marrow was used for transplant harvesting; in 19 cases (55.9 %) peripheral blood stem cells were harvested by means of cytapheresis. The CD34+ count in the transplant was 1.2–12.0 x 106 CD34+ cell/kg (median: 5.0 x 106 CD34+ cell/kg). Engraftment was observed in 79.4 % of cases (n = 27), graft failure in 17.7 % of cases (n = 6), and early posttransplant mortality in 2.9 % of cases (n = 1).

Conclusion. There was an increasing efficiency of search for a HLA-compatible unrelated HSC donor using a Russian BMDS search system for Russian residents with a graft quality similar to the one found in the international BMDW database.

Keywords: hematopoietic stem cell transplantation, unrelated bone marrow donor search, BMDS.

Received: July 13, 2016

Accepted: November 24, 2016

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WT1 Gene Overexpression in Oncohematological Disorders: Theoretical and Clinical Aspects (Literature Review)

REVIEWS , , ,

NN Mamaev, YaV Gudozhnikova, AV Gorbunova

R.M. Gorbacheva Scientific Research Institute of Pediatric Hematology and Transplantation; Academician I.P. Pavlov First St. Petersburg State Medical University, 6/8 L’va Tolstogo str., Saint Petersburg, Russian Federation, 197022

For correspondence: Nikolai Nikolaevich Mamaev, DSci, Professor, 6/8 L’va Tolstogo str., Saint Petersburg, Russian Federation, 197022; Tel.: +(7)911-760-50-86; e-mail: nikmamaev524@gmail.com

For citation: Mamaev NN, Gudozhnikova YaV, Gorbunova AV. WT1 Gene Overexpression in Oncohematological Disorders: Theoretical and Clinical Aspects (Literature Review). Clinical oncohematology. 2016;9(3):257-64 (In Russ).

DOI: 10.21320/2500-2139-2016-9-3-257-264

ABSTRACT

The article discusses recent data on the WT1 gene overexpression phenomenon in patients with acute leukemias, myelodysplastic syndromes, chronic myeloid leukemia, non-Hodgkin’s lymphomas, and multiple myeloma. It demonstrates that monitoring of the WT1 gene overexpression proves to be effective during the posttransplantation period, as well as after the induction chemotherapy. This approach may be applied in diagnosing the minimal residual disease and early detection of leukemia relapses, as well as their timely and controlled treatment. There are other promising fields of research, such as testing autografts for the presence or absence of tumor elements, as well as evaluation of the efficacy of induction chemotherapy in high risk patients.

Keywords: WT1 gene overexpression phenomenon, hematopoietic stem cell transplantation, chemotherapy, molecular treatment monitoring.

Received: February 8, 2016

Accepted: March 30, 2016

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Bone Marrow Transplantation in Patients with Acute Lymphoblastic Leukemia with Extremely Poor Prognosis: Literature Review and Case Report

BONE MARROW TRANSPLANTATION , , ,

NN Subbotina, AV Popa, IS Dolgopolov, VK Boyarshinov, RI Pimenov, VV Dailidite, GL Mentkevich

N.N. Blokhin Russian Cancer Research Center, 24 Kashirskoye sh., Moscow, Russian Federation, 115478

For correspondence: Natal’ya Nikolaevna Subbotina, PhD, 24 Kashirskoye sh., Moscow, Russian Federation, 115478; Tel.: +7(499)324-45-08; e-mail: natik-23@yandex.ru

For citation: Subbotina N.N., Popa A.V., Dolgopolov I.S., Boyarshinov V.K., Pimenov R.I., Dailidite V.V., Mentkevich G.L. Bone Marrow Transplantation in Patients with Acute Lymphoblastic Leukemia with Extremely Poor Prognosis: Literature Review and Case Report. Klin. Onkogematol. 2015; 8(3): 331-6. (In Russ.)

ABSTRACT

The difference in the survival rate between patients receiving the chemotherapy alone and those receiving the chemotherapy with hematopoietic stem cell transplantation (HSCT) becomes more significant with the increased number of acute lymphoblastic leukemia (ALL) risk factors. Myeloablative conditioning regimens remain a gold standard before HSCT in children and young adults with ALL. The traditional TBI-CPM based conditioning regimen followed by HSCT from related HLA identical donor demonstrates the highest survival rates. The survival rate of patients with ALL relapses after allogeneic HSCT remains low. The second HSCT is the only possible therapeutic option that provides a longer survival rate for not more than 10–15 % of patients. Delayed relapses after the first HSCT and patient’s age less than 10 y.o. are statistically significant factors of a better prognosis. The article describes author’s own experience in the management of an ALL high-risk group patients who have undergone chemotherapy, 3 allogeneic related HSCT with involvement of several donors, as well as an additional transfusion of peripheral blood stem cells obtained from the second HLA matching donor. The patient remains under medical supervision in the N.N. Blokhin Russian Cancer Research Center by the date of composition of this paper (23 months after a haploidentical HSCT).

Keywords: acute lymphoblastic leukemia, extremely poor prognosis, hematopoietic stem cell transplantation, conditioning regimen.

Received: March 3, 2015

Accepted: June 3, 2015

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REFERENCES

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Molecular Monitoring of WT1 Gene Expression Degree in Acute Myeloid Leukemias after Allogeneic Hematopoietic Stem Cell Transplantation

BONE MARROW TRANSPLANTATION , , , , ,

N.N. Mamaev, A.V. Gorbunova, I.M. Barkhatov, Ya.V. Gudozhnikova, T.L. Gindina, V.A. Katerina, E.V. Volchkov, A.L. Alyanskii, E.V. Babenko, O.A. Slesarchuk, N.V. Stancheva, S.N. Bondarenko, B.V. Afanas’ev

R.M. Gorbacheva Scientific Research Institute of Pediatric Hematology and Transplantation; Academician I.P. Pavlov First St. Petersburg State Medical University, 6/8 L’va Tolstogo str., Saint Petersburg, Russian Federation, 197022

For correspondence: Nikolai Nikolaevich Mamaev, DSci, Professor, 6/8 L’va Tolstogo str., Saint Petersburg, Russian Federation, 197022; Tel.: +7(812)233-12-43; e-mail: nikmamaev524@gmail.com

For citation: Mamaev NN, Gorbunova AV, Barkhatov IM, et al. Molecular Monitoring of WT1 Gene Expression Level in Acute Myeloid Leukemias after Allogeneic Hematopoietic Stem Cell Transplantation. Clinical oncohematology. 2015;8(3):309–20 (In Russ).

ABSTRACT

Objective. To evaluate the possibility of serial analysis of WT1 gene expression level for prediction and diagnosis of post-transplant acute myeloid leukemia (AML) relapses.

Methods. Serial analyses of WT1 gene expression were performed using quantitative real-time PCR during the post-transplant period of 34 patients with AML. All patients underwent allogeneic hematopoietic stem cell transplantation: unrelated (n = 22), related (n = 12), including haploidentical (n = 4). 5 of 34 patients had AML transformed from the myelodysplastic syndromes (MDS). In addition, the level of donor chimerism and the bone marrow/peripheral blood blast cells counts were evaluated. AML1/ETO (n = 4) or EVI1 (n = 4) gene expression degrees were measured in 8 patients in order to compare those with the WT1 gene expression.

Results. Based on obtained data on the WT1 gene expression, two equal subgroups of patients were formed. The first one consisted of patients with stable normal expression of the investigated molecular indicator during the post-transplant period, whereas the second group consisted of patients with impaired expression. The initial level of WT1 gene expression almost did not depend on both cytological and cytogenetic AML subtypes. During the post-transplant period, the WT1 gene expression degree correlated with that of AML1/ETO or EVI1. Increased WT1 gene expression take the lead over the decreased donor chimerism and blast cell count increase in bone marrow and blood typical for post-transplant relapses of AML.

Conclusion. The higher level of WT1 gene expression may serve not only as a marker for timely diagnosis of post-transplant relapses in AML patients, but also as a monitoring parameter for testing their treatment quality.

Keywords: acute myeloid leukemias, hematopoietic stem cell transplantation, WT1 gene expression monitoring, AML1/ETO and EVI1, diagnosis of post-transplant relapses, molecular monitoring of treatment.

Received: March 19, 2015

Accepted: June 1, 2015

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Stable donor hematopoiesis reconstitution after post-transplantation relapse of acute myeloid leukemia in patient with inv(3)(q21q26), –7 and EVI1 oncogene overexpression treated by donor lymphocyte infusions and hypomethylating agents

BONE MARROW TRANSPLANTATION , , , , , ,

N.N. Mamaev, A.V. Gorbunova, T.L. Gindina, O.A. Slesarchuk, V.N. Ovechkina, S.N. Bondarenko, O.V. Goloshchapov, V.M. Kravtsova, and B.V. Afanasev

I.P. Pavlov Saint Petersburg State Medical University, R.M. Gorbacheva Institute of Pediatric Oncology, Hematology and Transplantology, Saint Petersburg, Russian Federation

ABSTRACT

We present the case of successful treatment of post-transplantation relapse of prognostically unfavorable AML with inv(3)(q21q26), –7 and EVI1 oncogene overexpression, when stable donor hematopoiesis reconstitution was achieved due to one high-dose cytarabine course, DLI, and hypomethylating agents (decitabine, 5-azacitidine). Possible molecular mechanisms of this effect are discussed with respect to the new approaches to management of such patients.

Keywords: acute myeloid leukemia, inv(3)(q21q26), EVI1 high expression, hematopoietic stem cell transplantation, relapse, treatment, donor lymphocyte infusions, hypomethylating agents.

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REFERENCES

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Current therapies for AL amyloidosis: literature review and our data

LYMPHOID TUMORS , , ,

A.G. Smirnova1, S.N. Bondarenko1, A.A. Kisina2, A.V. Smirnov2, A. Tsander 3, and B.V. Afanasyev1

1 R.M. Gorbacheva Institute of Pediatric Hematology and Transplantology, I.P. Pavlov State Medical University, Saint Petersburg, Russian Federation

2 Research Institute of Nephrology, I.P. Pavlov State Medical University, Saint Petersburg, Russian Federation

3 Universitare Transplantations-Centrum, Universitatsklinikum Hamburg-Eppendorf, Hamburg, Germany

ABSTRACT

AL amyloidosis is a relatively rare condition belonging to plasma cell dyscrasias with very heterogeneous clinical presentation and poor prognosis. This article presents a brief description of AL amyloidosis, current therapies, and our own statistics on new combination therapy outcomes. We included 46 patients with confirmed AL amyloidosis who received autologous stem cell transplantation and standard combination chemotherapy, including melphalan + dexamethasone or bortezomib + dexamethasone.

Keywords: AL amyloidosis, therapy, hematopoietic stem cell transplantation, melphalan, bortezomib.

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