Outcome of Classical Hodgkin’s Lymphoma Treatment Based on High-Dose Chemotherapy and Autologous Hematopoietic Stem Cell Transplantation: The Experience in the NI Pirogov Russian National Medical Center of Surgery

NE Mochkin, VO Sarzhevskii, YuN Dubinina, EG Smirnova, DA Fedorenko, AE Bannikova, DS Kolesnikova, VS Bogatyrev, NM Faddeev, VYa Mel’nichenko

NI Pirogov Russian National Medical Center of Surgery, 70 Nizhnyaya Pervomaiskaya str., Moscow, Russian Federation, 105203

For correspondence: Nikita Evgen’evich Mochkin, MD, PhD, 70 Nizhnyaya Pervomaiskaya str., Moscow, Russian Federation, 105203; Tel.: 8(495)603-72-17; e-mail: nickmed@yandex.ru

For citation: Mochkin NE, Sarzhevskii VO, Dubinina YuN, et. al. Outcome of Classical Hodgkin’s Lymphoma Treatment Based on High-Dose Chemotherapy and Autologous Hematopoietic Stem Cell Transplantation: The Experience in the NI Pirogov Russian National Medical Center of Surgery. Clinical oncohematology. 2018;11(3):234–40.

DOI: 10.21320/2500-2139-2018-11-3-234-240


ABSTRACT

Aim. To estimate the long-term outcome of the programmed treatment of classical Hodgkin’s lymphoma (cHL) including high-dose chemotherapy (HDCT) and autologous hematopoietic stem cell transplantation (auto-HSCT) as well as the effect of various factors on the achieved results in a single-center study.

Materials & Methods. In the A.A. Maksimov Clinical Center of Hematology and Cellular Therapy of the NI Pirogov Russian National Medical Center of Surgery 260 cHL patients received HDCT combined with auto-HSCT within the period from December 2006 to March 2017. The median age was 29 years (range 17–62). The study included 40 % men (n = 104), and 60 % women (n = 156). The median pretransplantation chemotherapy line was 3 (range 2–9). At this stage, prior to auto-HSCT, complete remission (CR) rate was 26.5 %, partial remission (PR) rate was 52.3 %, disease stabilisation rate was 13.5 %. HDCT with auto-HSCT was applied beyond progression as a salvage therapy in 7.7 % of patients. In 79.6 % of patients the standard BEAM and CBV conditioning regimens were used.

Results. After HDCT combined with auto-HSCT overall 5-year survival (OS) of 260 cHL patients was 74 %, and 5-year progression-free survival (PFS) was 48 %, which corresponds to the results of some international studies. 5-year OS rates were significantly higher after HDCT and auto-HSCT performed during the first CR or PR (85 %) vs the second and subsequent CR and PR (71 %). Neither gender (= 0.4) nor ECOG status (= 0.2) effects on OS and PFS were revealed. 5-year OS rates were significantly higher after HDCT and auto-HSCT performed during CR or PR (82 %) vs disease stabilisation and progression (54 %) as well as upon achieving CR (93 %) vs PR (77 %).

Conclusion. In cHL tumor sensitivity to chemotherapy is the essential indication for HDCT combined with auto-HSCT. The optimal time for HDCT and auto-HSCT in cHL is the first CR/PR, and the best treatment outcome is achieved in patients with complete response prior to HDCT and auto-HSCT.

Keywords: classical Hodgkin’s lymphoma, high-dose chemotherapy, autologous hematopoietic stem cell transplantation.

Received: February 9, 2018

Accepted: May 3, 2018

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Hematopoietic Stem Cell Collection in Multiple Myeloma Patients: Influence of the Lenalidomide-Based Therapy and Mobilization Regimen Prior to Auto-HSCT

II Kostroma, AA Zhernyakova, ZhV Chubukina, IM Zapreeva, SA Tiranova, AV Sel’tser, NYu Semenova, SS Bessmel’tsev, AV Chechetkin, SV Gritsaev

Russian Research Institute of Hematology and Transfusiology, 16 2-ya Sovetskaya str., Saint Petersburg, Russian Federation, 191024

For correspondence: Ivan Ivanovich Kostroma, MD, PhD, 16 2-ya Sovetskaya str., Saint Petersburg, Russian Federation, 191024; Теl.: +7(921)784-82-82; e-mail: obex@rambler.ru

For citation: Kostroma II, Zhernyakova AA, Chubukina ZhV, et al. Hematopoietic Stem Cell Collection in Multiple Myeloma Patients: Influence of the Lenalidomide-Based Therapy and Mobilization Regimen Prior to Auto-HSCT. Clinical oncohematology. 2018;11(2):192–7.

DOI: 10.21320/2500-2139-2018-11-2-192-197


ABSTRACT

Background. A prompt graft acceptance is essential for positive autologous hematopoietic stem cell transplantation (auto-HSCT) outcome in multiple myeloma patients (MM). Prompt and favourable hematopoietic regeneration is associated with CD34+ cell count in a transplant. Although the indicators of low autotransplant cellularity have been defined, the practical application of new drug products and HSC mobilization regimens strengthens the relevance of determining their influence on the transplant quality.

Aim. To determine the factors that are associated with low efficacy of auto-HSCT in MM patients and to evaluate the impact of lenalidomide during induction period and of vinorelbine as a mobilization regimen on the prognosis.

Materials & Methods. The authors performed a retrospective analysis of autotransplant collection results in 68 MM patients treated with two mobilization regimens: 3 g/m2 cyclophosphamide with granulocyte colony-stimulating factor (G-CSF) and 30 mg/m2 vinorelbine with G-CSF. Mobilization was aimed at collecting not less than 2–4 × 106 CD34+ cells per kg body mass. CD34+ cell count was determined by four-color analysis on the Cytomics FC 500 laser flow cytometer.

Results. The analysis showed that age or MM immunochemical specificity were not associated with CD34+ cell count in the transplant. Prior lenalidomide treatment compared to therapy without immunomodulators (4.1 × 106/kg vs. 7.76 × 106/kg) tends to decrease CD34+ count (р = 0.066). Cyclophosphamide included into mobilization regimen compared to vinorelbine (3.96 × 106/kg vs. 6.8 × 106/kg) significantly increased CD34+ cell count (р = 0.022).

Conclusion. The decrease of CD34+ cell count in the autotransplant of the MM patients treated with lenalidomide prior to auto-HSC collection, and a lower mobilization activity of vinorelbine provide a basis for a differentiated selection of mobilization regimens. Vinorelbine may be administered to patients with a single auto-HSCT, i.e. elderly people and patients with complete response. In case of substantial lenalidomide treatment prior to auto-HSCT, intermediate-dose cyclophosphamide is preferred.

Keywords: auto-HSCT, multiple myeloma, mobilization regimen, cyclophosphamide, vinorelbine, lenalidomide, predictors.

Received: November 29, 2017

Accepted: February 9, 2018

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Autologous Hematopoietic Stem Cell Transplantation in Multiple Myeloma in the Era of New Drugs

OV Pirogova, EI Darskaya, VV Porunova, OV Kudyasheva, AG Smirnova, IS Moiseev, EV Babenko, BV Afanas’ev

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: Ol’ga Vladislavovna Pirogova, MD, PhD, 6/8 L’va Tolstogo str., Saint Petersburg, Russian Federation, 197022; e-mail: dr.pirogova@gmail.com.

For citation: Pirogova OV, Darskaya EI, Porunova VV, et al. Autologous Hematopoietic Stem Cell Transplantation in Multiple Myeloma in the Era of New Drugs. Clinical oncohematology. 2018;11(2):187–91.

DOI: 10.21320/2500-2139-2018-11-2-187-191


ABSTRACT

Background & Aims. The present retrospective single-center study analysed the impact of high-dose chemotherapy with melphalan with subsequent autologous hematopoietic stem cell transplantation (auto-HSCT) on survival in multiple myeloma (MM) in the era of new induction regimens.

Materials & Methods. The clinical trial included 133 MM patients aged from 31.2 to 78.2 years (the median age was 55.3 years). There were 66 female and 67 male patients. Bortezomib-based regimens as first-line treatment were administered in 133 MM patients, 74 of them received high-dose chemotherapy with melphalan and either single (n = 25), or double (n = 49) auto-HSCT as consolidation therapy in the period from 2006 to 2016.

Results. The overall 5-year survival (OS) rates were 86.5 % for the auto-HSCT treated group vs. 72.9 % for the non-auto-HSCT treated group (= 0.03); 5-year progression-free survival (PFS) rates were 64.9 vs. 39 % for the auto-HSCT and non-auto-HSCT treated groups, respectively (= 0.0016). MM relapse/progression occurred more frequently in the non-auto-HSCT treated patients (52.5 vs. 28.4 %; = 0.0016). In multivariate analysis the age above 60 was determined as prognostic factor of lower PFS and increase in relapse/progression rate (= 0.004 and = 0.04, respectively). The variant of monoclonal protein (Bence-Jones myeloma) was determined as prognostic factor of higher OS and decrease in relapse/progression rate (= 0.02 and = 0.04, respectively). Complete nonresponsiveness to induction therapy has proved to be an independent predictor of both poor OS and PFS (= 0.04 and = 0.041, respectively). 2-year bortezomib-based maintenance therapy following the auto-HSCT treatment resulted in a statistically significant improvement in 5-year PFS (67.4 vs. 60.7 %; = 0.03) and a decrease in relapse/progression frequency (26.1 vs. 32.1 %; = 0.05).

Conclusion. High-dose chemotherapy with melphalan with subsequent auto-HSCT is an effective MM treatment strategy, and a subsequent long-term maintenance therapy results in a PFS improvement and a decrease in relapse/progression frequency.

Keywords: multiple myeloma, autologous hematopoietic stem cell transplantation, maintenance therapy.

Received: November 20, 2017

Accepted: February 9, 2018

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

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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Classification of Conditioning Regimens for Bone Marrow Transplantation: Historical Background and Current Perspectives

KN Melkova, GD Petrova, NV Gorbunova, TZ Chernyavskaya, OP Trofimova

NN Blokhin National Medical Cancer Research Center, 24 Kashirskoye sh., Moscow, Russian Federation, 115478

For correspondence: Kapitolina Nikolaevna Melkova, PhD, 24 Kashirskoye sh., Moscow, Russian Federation, 115478; e-mail: frolov63@bk.ru

For citation: Melkova KN, Petrova GD, Gorbunova NV, et al. Classification of Conditioning Regimens for Bone Marrow Transplantation: Historical Background and Current Perspectives. Clinical oncohematology. 2017;10(4):494–500 (In Russ).

DOI: 10.21320/2500-2139-2017-10-4-494-500


ABSTRACT

Hematopoietic stem cells transplantation is a current standard treatment for many oncohematological diseases. The milestone of any type of transplantation is the choice of conditioning regimen. This article presents the principles of classification of conditioning regimens in terms of myeloablativity and discusses the concepts of “autologous transplantation”, “high-dose chemotherapy supported by hematopoietic stem cells”, “allogeneic transplantation” and “immunotherapy”. Up-to-date uniform classification of conditioning regimens may serve an important prognostic component in assessing both the risks and efficacy of hematopoietic stem cells transplantation.

Keywords: conditioning regimens, allogeneic hematopoietic stem cell transplantation, autologous hematopoietic stem cell transplantation, total therapeutic exposure, acute leukemia, Hodgkin’s lymphoma, multiple myeloma.

Received: March 29, 2017

Accepted: July 8, 2017

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The Role of Hypomethylating Agents Prior to Allogeneic Hematopoietic Stem Cells Transplantation in Acute Myeloid Leukemia and Myelodysplastic Syndrome

VN Ovechkina1, SN Bondarenko1, EV Morozova1, IS Moiseev1, AA Osipova1, TL Gindina1, AI Shakirova1, TA Bykova1, AD Kulagin1, IA Samorodova2, EV Karyakina3, EA Ukrainchenko4, LS Zubarovskaya1, BV Afanas’ev1

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

2 Municipal Clinical Hospital No. 31, 3 Dinamo pr-t, Saint Petersburg, Russian Federation, 197110

3 Municipal Hospital No. 15, 4 Avangardnaya str., Saint Petersburg, Russian Federation, 198205

4 Aleksandrov Hospital, 4 Solidarnosti pr-t, Saint Petersburg, Russian Federation, 193312

For correspondence: Varvara Nikolaevna Ovechkina, 6/8 L’va Tolstogo str., Saint Petersburg, Russian Federation, 197022; Tel.: +7(812)338-62-72; e-mail ovetchkina@gmail.com

For citation: Ovechkina VN, Bondarenko SN, Morozova EV, et al. The Role of Hypomethylating Agents Prior to Allogeneic Hematopoietic Stem Cells Transplantation in Acute Myeloid Leukemia and Myelodysplastic Syndrome. Clinical oncohematology. 2017;10(3):351–7 (In Russ).

DOI: 10.21320/2500-2139-2017-10-3-351-357


ABSTRACT

Background & Aims. The aim of the study was to evaluate the efficacy and safety of azacytidine and decitabine prior to allogeneic hematopoietic stem cell transplantation (allo-HSCT) in acute myeloid leukemia (AML), myelodysplastic syndrome (MDS), chronic myelomonocytic leukemia and juvenile myelomonocytic leukemia.

Materials & Methods. The research included 62 patients who received hypomethylating agents (HMA) prior to allo-HSCT. The median age was 28 years (range from 1 to 68 years), the study population consisted of 27 (43.5 %) women and 35 (56.5 %) men.

Results. The overall response (complete + partial remission) was observed in 42 % (n = 26) of cases. At the time of allo-HSCT no disease progression was observed in 41 (66 %) patients. The multivariant analysis showed the overall survival (OS) statistically significantly increased with the graft retention (hazard ratio [HR] 0.002; 95% confidence interval [95% CI] 0.001–0.74; p = 0.03), and also with the administration of HMA after allo-HSCT (HR 0.24; 95% CI 0.08–0.67; p = 0.007). The response (stabilisation, partial or complete remission) due to HMA administration prior to allo-HSCT (HR 6.4; 95% CI 0.75–54.0; p = 0.08) was associated with improved OS. The event-free survival (EFS) was significantly higher with the response to azacytidine and decitabine at the time of allo-HSCT (HR 38.9; 95% CI 1.3–1198.0; p = 0.03) and with the graft retention (HR 0.02; 95% CI 0.005–0.1; p = 0.001). In patients with MDS compared with AML (HR 2.3; 95% CI 0.9–22.0; p = 0.08), there was a tendency to EFS improvement. Progression-free survival rates were higher in patients with a number of blast cells in the bone marrow less than 31 % at the time of diagnosis (HR 1.1; 95% CI 1.1–9.9; p = 0.01).

Conclusion. The use of azacytidine and decitabine prior to allo-HSCT allows to safely control the tumor mass in patients with MDS and to maintain the achieved remission with AML. In patients with a response to HMA, the best OS and EFS values are seen after allo-HSCT.

Keywords: acute myeloid leukemia, myelodysplastic syndrome, allogeneic hematopoietic stem cell transplantation, hypomethylating agents, azacitidine, decitabine.

Received: December 19, 2016

Accepted: March 9, 2017

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  25. Овечкина В.Н., Бондаренко С.Н., Морозова Е.В. и др. Острый миелобластный лейкоз и миелодиспластический синдром: применение азацитидина с профилактической и превентивной целью после аллогенной трансплантации гемопоэтических стволовых клеток. Клиническая онкогематология. 2017;10(1):45–51. doi: 10.21320/2500-2139-2017-10-1-45-51. [Ovechkina VN, Bondarenko SN, Morozova EV, et al. Acute Myeloblastic Leukemia and Myelodysplastic Syndrome: Azacitidine for Prophylactic and Preventive Purposes after Allogeneic Hematopoietic Stem Cell Transplantation. Clinical oncohematology. 2017;10(1):45–51. doi: 10.21320/2500-2139-2017-10-1-45-51. (In Russ)]
  26. Craddock Ch, Jilani N, Siddique Sh, et al. Tolerability and Clinical Activity of Post-Transplantation Azacitidine in Patients Allografted for Acute Myeloid Leukemia Treated on the RICAZA Trial. Biol Blood Marrow Transplant. 2016;22(2):385–90. doi: 10.1016/j.bbmt.2015.09.004.

Acute Lymphoblastic Leukemia with t(4;11)(q21;q23)/KMT2A-AFF1 Translocation: The Results of Allogeneic Hematopoietic Stem Cells Transplantation in Children and Adults

TL Gindina, NN Mamaev, OV Paina, AS Borovkova, PV Kozhokar’, OA Slesarchuk, YaV Gudozhnikova, EI Darskaya, AL Alyanskii, SN Bondarenko, LS Zubarovskaya, BV Afanas’ev

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

For correspondence: Tat’yana Leonidovna Gindina, PhD, 6/8 L’va Tolstogo str., Saint Petersburg, Russian Federation, 197022; Tel.: +7(812)233-12-43; e-mail: cytogenetics.bmt.lab@gmail.com

For citation: Gindina TL, Mamaev NN, Paina OV, et al. Acute Lymphoblastic Leukemia with t(4;11)(q21;q23)/KMT2A-AFF1 Translocation: The Results of Allogeneic Hematopoietic Stem Cells Transplantation in Children and Adults. Clinical oncohematology. 2017;10(3):342–50 (In Russ).

DOI: 10.21320/2500-2139-2017-10-3-342-350


ABSTRACT

Aim. The aim was to evaluate the results of the allogeneic hematopoietic stem cells transplantation (allo-HSCT) in children and adults with the most prognostically unfavorable acute lymphoblastic leukemia (ALL) with t(4;11)(q21;q23)/KMT2A-AFF1 translocation.

Methods. We examined 21 patients (12 females, 9 males) aged from 3 months to 48 years (median 18.9 years). The analysis of prognostic factors of overall (OS) and event-free survival (EFS) after allo-HSCT in patients of different age groups with various clinical, transplantation and cytogenetic characteristics was performed. Allo-HSCT from HLA-compatible related and unrelated donors, as well as haploidentical allo-HSCT were performed in 4, 9 and 8 patients of age groups < 1 year, 1–18 years, and >18 years, respectively. In 10 (48 %) patients, allo-HSCT was performed in the first remission, in 2 (10 %) patients in the second remission, and in 9 (43 %) patients during the disease relapse.

Results. In 8 (38 %) patients, the only chromosomal disorder was the translocation t(4;11)(q21;q23). Additional changes in chromosomes were found in 11 (52 %) patients. In 8 (38 %) of them, 3 or more chromosomal abnormalities in the karyotype were found. According to the results of a univariant analysis, the OS and EFS were significantly different in patients with allo-HSCT performed in the first remission and at other stages of ALL (in the second remission and in relapse: < 0.001 in both cases), as well as in patients with or without 3 or more cytogenetic disorders in the karyotype (p = 0.04 in both cases). The multivariant analysis showed that the only independent prognostic factor affecting the OS and EFS in ALL patients with t(4;11) was the allo-HSCT, including the haploidentical procedure, during the first complete hematological and molecular remission (p = 0.002 and p = 0.0004, respectively).

Conclusion. ALL with t(4;11)/KMT2A-AFF1 was as an absolute indication for allo-HSCT in first remission, including children of < 1 year age group. Satisfactory results can be obtained with the use of haploidentical transplantation from the parents. This approach eliminates the search in the registers completely HLA-compatible donor and facilitates the treatment procedure.

Keywords: acute lymphoblastic leukemia, t(4;11)/KMT2A-AFF1 translocation, allogeneic HSCT.

Received: January 17, 2017

Accepted: May 10, 2017

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REFERENCES

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Acute Myeloblastic Leukemia and Myelodysplastic Syndrome: Azacitidine for Prophylactic and Preventive Purposes after Allogeneic Hematopoietic Stem Cell Transplantation

VN Ovechkina1, SN Bondarenko1, EV Morozova1, IS Moiseev1, OA Slesarchuk1, AG Smirnova1, OS Uspenskaya2, YaV Gudozhnikova1, AA Osipova1, VS Sergeev1, NN Mamaev1, LS Zubarovskaya1, BV Afanas’ev1

1 RM Gorbacheva Scientific Research Institute of Pediatric Hematology and Transplantation; Academician IP Pavlov First St. Petersburg State Medical University, 12 Rentgena str., Saint Petersburg, Russian Federation, 197022

2 Leningrad District Clinical Hospital, 45–49 Lunacharskogo pr-t, Saint Petersburg, Russian Federation, 194291

For correspondence: Varvara Nikolaevna Ovechkina, 6/8 L’va Tolstogo str., Saint Petersburg, Russian Federation, 197022; Tel. +7(812)338-62-72; e-mail: ovetchkina@gmail.com

For citation: Ovechkina VN, Bondarenko SN, Morozova EV, et al. Acute Myeloblastic Leukemia and Myelodysplastic Syndrome: Azacitidine for Prophylactic and Preventive Purposes after Allogeneic Hematopoietic Stem Cell Transplantation. Clinical oncohematology. 2017;10(1):45-51 (In Russ).

DOI: 10.21320/2500-2139-2017-10-1-45-51


ABSTRACT

Aim. To evaluate the effectiveness of preventive and prophylactic post-transplantation therapy using azacitidine (5-AZA) in patients at high risk of post-transplantation relapse.

Methods. 136 patients were included in the study performed by the pairwise comparison: 68 of them received 5-AZA after allo-HSCT and 68 patients were included in the historical control group. 5-AZA was prescribed for prophylactic or preventive purposes. The results were assessed according to the OS, RR, EFS, DUM, and relapse-free and GVHR-free survival.

Results. 1-year OS was 76 % in the 5-AZA group (95% CI 60–84 %) and 44 % in the reference group (95% CI 33–55 %) (= 0.001); 2-year OS was 63 % (95% CI 39–67 %) and 37 % (95% CI 26–48 %) (= 0.007), respectively. The relapse rate (RR) in the 5-AZA group was 34 % (95% CI 22–46 %) during 1 year and 51 % (95% CI 38–64 %) in the reference group (= 0.02). 1- and 2-year disease unrelated mortality (DUM) was similar: 5 % in the 5-AZA group (95% CI 0.1–14.0 %) and 25 % (95% CI 13–37 %) in the reference group (= 0.005). 1-year EFS was 76 % in the 5-AZA group (95% CI 61–85 %) and 44 % in the reference group (95% CI 33–55 %) (= 0.001); 2-year EFS was 63 % (95% CI 39–67 %) and 37 % (95% CI 26–48 %) (= 0.01), respectively. 1-year relapse-free and GVHR-free survival was 55 % in the 5-AZA group (95% CI 41–69 %) and 28 % in the reference group (95% CI 17–39 %) (= 0.001); 2-year relapse-free and GVHR-free survival was 47 % (95% CI 32–62 %) and 27 % (95% CI 17–37 %) (= 0.002), respectively.

Conclusion. The use of 5-AZA for prophylactic and preventive purposes after allo-HSCT does not increase the risk of GVHR and DUM, does not suppress the GVL effect and can be used in combination with the donor lymphocyte infusion (DLI). The therapy with 5-AZA is safe during the early period after allo-HSCT. The drug does not suppress the GVL effect and can be used in high risk patients to prevent early post-transplantation relapse. The use of 5-AZA in combination with DLI does not increase the incidence of severe GVHR.

Keywords: acute myeloblastic leukemia, myelodysplastic syndrome, allogeneic hematopoietic stem cell transplantation, hypomethylating therapy, azacitidine.

Received: July 18, 2016

Accepted: December 17, 2016

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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

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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REFERENCES

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Prevention of Acute Graft-Versus-Host Reaction after Allogeneic Unrelated Hematopoietic Stem Cell Transplantation: Comparison of Effectiveness of Treatment Regimens Based on Anti-Thymocyte Globulin and Cyclophosphamide

OV Pirogova, IS Moiseev, EV Babenko, OA Slesarchuk, OV Paina, SN Bondarenko, EV Morozova, AL Alyanskii, 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: Ol’ga Vladislavovna Pirogova, 6/8 L’va Tolstogo str., Saint Petersburg, Russian Federation, 197022; Tel: +7(812)338-62-65; e-mail: dr.pirogova@gmail.com

For citation: Pirogova OV, Moiseev IS, Babenko EV, et al. Prevention of Acute Graft-Versus-Host Reaction after Allogeneic Unrelated Hematopoietic Stem Cell Transplantation: Comparison of Effectiveness of Treatment Regimens Based on Anti-Thymocyte Globulin and Cyclophosphamide. Clinical oncohematology. 2016;9(4):391–97 (In Russ).

DOI: 10.21320/2500-2139-2016-9-4-391-397


ABSTRACT

Background & Aims. So far there is no data presented on the effectiveness of prevention of the graft-versus-host reaction (GVH) using post-transplant cyclophosphamide (PTCy) prescribed after unrelated donor allogeneic hematopoietic stem cell transplantation (allo-HSCT). The aim of this study is to evaluate the incidence of acute and chronic GVH, the transplantation-associated mortality rate, the event-free and overall survival rates, as well as the toxicity profile and the incidence of infectious complications in the study group using cyclophosphamide for GVH prevention; the other aim is to carry out a comparative analysis of the obtained results with the historical control group.

Methods. 110 adult patients were enrolled in a clinical study to evaluate the effectiveness of GVH prevention, using PTCy (No. NCT02294552). In order to prevent GVH, the study group (PTCy group) received cyclophosphamide, tacrolimus and mycophenolate mofetil (MMF). The historical control group (ATG group) consisted of 160 patients prescribed with a GVH prevention regimen including anti-thymocyte globulin (ATG), calcineurin inhibitors, and methotrexate or MMF. Peripheral blood stem cells were used as a source of the transplant.

Results. The cumulative incidence of II–IV degree acute GVH (18.2 % vs. 40.4 %, respectively; < 0.0001), III–IV degree GVH (4.5 % vs. 22.5 %, respectively; < 0.0001), and chronic GVH (21.7 % vs. 40.6 %, respectively; < 0.0001) was significantly lower in the PTCy group than in the ATG group. Prevention of GVH based on PTCy was associated with the reduction in transplant-associated mortality (12.7 % vs. 33.7 %, respectively; = 0.003), increased overall survival (70.9 % vs. 44.4 %, respectively; < 0.001), event-free survival (68.2 % vs. 38.1 %, respectively; < 0.001) and GVH- and relapse-free survival rates (59.1 % vs. 16.3 %, respectively; = 0.001). Prevention of GVH using PTCy (as compared to ATG) was less toxic, accompanied by a reduction in the incidence veno-occlusive disease (2.7 % vs. 10.9 %, respectively; = 0.016), severe mucositis (69.5 % vs. 87.6 %, respectively; < 0.001), and invasive mycosis (7.2 % vs. 29 %, respectively; < 0.001).

Conclusion. A combination of cyclophosphamide with tacrolimus and MMF is an effective regimen for GVH prevention in patients after allo-HSCT from an unrelated donor.


Keywords: graft-versus-host reaction, GVH prevention, allo-HCST, cyclophosphamide, anti-thymocyte globulin.

Received: March 30, 2016

Accepted: May 4, 2016

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