autologous hematopoietic stem cell transplantation

Potential Predictors and Response Quality after Autologous Hematopoietic Stem Cell Transplantation in Multiple Myeloma

AUTOIMMUNE THROMBOCYTOPENIA ,

II Kostroma1, ZhYu Sidorova1, NYu Semenova1, AA Zhernyakova1, RR Sabitova1, SP Svitina1, EI Stepchenkova2,3, SS Bessmeltsev1, AV Chechetkin1, SV Gritsaev1

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

2 Saint Petersburg State University, 7/9 Universitetskaya emb., Saint Petersburg, Russian Federation, 199034

3 NI Vavilov Institute of General Genetics, Saint Petersburg branch, 7/9 Universitetskaya emb., Saint Petersburg, Russian Federation, 199034

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

For citation: Kostroma II, Sidorova ZhYu, Semenova NYu, et al. Potential Predictors and Response Quality after Autologous Hematopoietic Stem Cell Transplantation in Multiple Myeloma. Clinical oncohematology. 2021;14(3):333–9. (In Russ).

DOI: 10.21320/2500-2139-2021-14-3-333-339

ABSTRACT

Aim. To assess the rate of cases without antitumor response quality improvement after high-dose chemotherapy (HDCT) with autologous hematopoietic stem cell transplantation (auto-HSCT) in multiple myeloma (MM). To assess the rate of allelic variants of IL1B, IL6, IL10, TNF genes and the status of hematopoietic niche cells as potential predictors of auto-HSCT efficacy.

Materials & Methods. A retrospective analysis was based on the data of 84 MM patients who received 112 auto-HSCTs, including 84 first and 28 repeated courses. Response variants were estimated according to IWG criteria. Molecular profiling of IL1B, IL6, IL10, and TNF genes was performed using polymerase chain reaction (PCR) with subsequent analysis of restriction fragment length polymorphism of PCR products. To analyze the status of hematopoietic niche cells histological, immunohistochemical, and morphometric methods were applied.

Results. The first auto-HSCT yielded response quality improvement in 29 (54.7 %) out of 84 patients. The rate of complete response was significantly higher in patients who showed very good partial response before HDCT with auto-HSCT, than in patients with partial response (PR), i.e., 57.9 % and 18.2 %, respectively (р = 0.005). No differences were identified in the groups of patients with other clinical and hematological parameters. After the second auto-HSCT in 4 out of 6 patients with PR the response variant did not change. A significant decrease of MM activity was associated with IL6 (–174С) mutant allele carrier status of 81.3 % vs. 41.6 % in the group with the unchanged response variant (р = 0.05). Response quality improvement was also related to a large number of cells on the endosteum in histological specimens of bone marrow (р = 0.038).

Conclusion. The carrier status of IL6 (–174С) pathologic allele as well as the number of cells on the endosteum in histological specimens of bone marrow can be regarded as predictors of response quality improvement or lack thereof in MM patients after auto-HSCT.

Keywords: multiple myeloma, autologous hematopoietic stem cell transplantation, IL6 gene, hematopoietic niche.

Received: January 29, 2021

Accepted: May 30, 2021

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Retrospective Survival Analysis of Multiple Myeloma Patients after Autologous Hematopoietic Stem Cell Transplantation

AUTOIMMUNE THROMBOCYTOPENIA ,

II Kostroma1, AA Zhernyakova1, IM Zapreeva1, ZhYu Sidorova1, NYu Semenova1, EV Karyagina2, EI Stepchenkova3,4, SS Bessmeltsev1, AV Chechetkin1, SV Gritsaev1

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

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

3 Saint Petersburg State University, 7/9 Universitetskaya emb., Saint Petersburg, Russian Federation, 199034

4 NI Vavilov Institute of General Genetics, Saint Petersburg branch, 7/9 Universitetskaya emb., Saint Petersburg, Russian Federation, 199034

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

For citation: Kostroma II, Zhernyakova AA, Zapreeva IM, et al. Retrospective Survival Analysis of Multiple Myeloma Patients after Autologous Hematopoietic Stem Cell Transplantation. Clinical oncohematology. 2021;14(1):73–9. (In Russ).

DOI: 10.21320/2500-2139-2021-14-1-73-79

ABSTRACT

Background. Autologous hematopoietic stem cell transplantation (auto-HSCT) is an indispensable treatment stage in patients with newly diagnosed multiple myeloma (MM) who are, based on age and health status, eligible for high-dose chemotherapy with subsequent auto-HSCT. However, the issue of double (tandem) auto-HSCT feasibility remains unresolved.

Aim. To compare overall survival (OS) and progression-free survival (PFS) in MM patients after single and double (tandem) auto-HSCTs in clinical practice.

Materials & Methods. Retrospective analysis enrolled 83 MM patients divided into two groups: with single (n = 41) and double (n = 42) auto-HSCTs. Median age in groups 1 and 2 was 58 years (range 42–68) and 54 years (range 40–65), respectively. In these groups there were 16 (39 %) and 11 (26.2 %) patients ≥ 60 years old. The reference point of survival curve was the date of first (in group 1) and 2nd (in group 2) auto-HSCTs. In PFS assessment, completed event was the date of disease progression or relapse detection, including the biochemical one in case of specific therapy onset.

Results. Total number of patients with ≥ very good partial response before receiving auto-HSCT in group 1 was 23 (56.1 %), and in group 2 before receiving 2nd auto-HSCT it was 30 (71.4 %). Mel200 conditioning was administered to 53.7 % of patients in group 1. In group 2 this conditioning regimen was a priority in performing first auto-HSCT (83.3 % of patients) and was more rarely used in case of repeated transplantation (40.5 %). With median follow-up of 11 and 40.5 months in groups 1 and 2 no significant differences were identified either in median PFS (21 and 40 months; р = 0.154) or in median OS (not reached in both groups; p = 0.882). No differences between groups with respect to the time before relapse/progression or early relapse rate were observed.

Conclusion. Repeated auto-HSCT showed no additional antitumor effect. It can be accounted for by the lack of data on chromosome aberrations at the disease onset in most patients and by a small number of patients in the groups. Nevertheless, it was decided to limit the number of tandem auto-HSCTs and to perform 2nd transplantation mostly in case of late relapse/progression. New studies were initiated which will focus on the search of predictors associated with survival improvement in MM patients while performing double (tandem) auto-HSCTs.

Keywords: multiple myeloma, autologous hematopoietic stem cell transplantation, single auto-HSCT, double (tandem) auto-HSCTs, survival.

Received: July 15, 2020

Accepted: November 20, 2020

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Статистика Plumx английский

REFERENCES

  1. Бессмельцев С.С., Абдулкадыров К.М. Множественная миелома: руководство для врачей. М.: СИМК, 2016. 512 с.
    [Bessmeltsev SS, Abdulkadyrov KM. Mnozhestvennaya mieloma: rukovodstvo dlya vrachei. (Multiple myeloma: manual for physicians.) Moscow: SIMK Publ.; 2016. 512 p. (In Russ)]
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Autologous Hematopoietic Stem Cell Transplantation in Multiple Myeloma Treatment with and without the Use of Granulocyte Colony-Stimulating Factor in Post-Transplantation Period

AUTOIMMUNE THROMBOCYTOPENIA ,

SV Gritsaev, II Kostroma, AA Zhernyakova, IM Zapreeva, VN Chebotkevich, SS Bessmeltsev, AV Chechetkin

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; Tel.: 8(812)717-54-68; e-mail: obex@rambler.ru

For citation: Gritsaev SV, Kostroma II, Zhernyakova AA, et al. Autologous Hematopoietic Stem Cell Transplantation in Multiple Myeloma Treatment with and without the Use of Granulocyte Colony-Stimulating Factor in Post-Transplantation Period. Clinical oncohematology. 2020;13(3):289–94 (In Russ).

DOI: 10.21320/2500-2139-2020-13-3-289-294

ABSTRACT

Background. There exist different data on how the administration of granulocyte colony-stimulating factor (G-CSF) after autologous hematopoietic stem cell transplantation (auto-HSCT) affects the duration of post-transplantation agranulocytosis in multiple myeloma (MM) patients.

Aim. To study the effect of G-CSF, administered after auto-HSCT to MM patients, on the duration of neutrophil engraftment, febrile neutropenia rate, and hospitalization duration.

Materials & Methods. The trial included 36 MM patients aged 42–69 years (median 59 years), 16 of which were not treated with G-CSF (1st group), and 20 patients received a single injection of 6 mg pegylated G-CSF on Day +4 or Day +5 (2nd group).

Results. Patients of the 1st group were significantly younger than patients of the 2nd group: median 55.5 and 61 years, respectively (p = 0.006). There were no differences with respect to the number of patients who previously received lenalidomide, the overall and very good partial response rate, the number of the first and repeated auto-HSCTs, and the number of melphalan conditioning regimens. The patients who received G-CSF engrafted neutrophils on day 11 (median) after auto-HSCT, i.e. earlier than patients without G-CSF administration who engrafted neutrophils on day 13 (p = 0.006). In the 1st group intravenous antibiotics were administered for a longer time than in the group with G-CSF: median 13 and 11 days, respectively (p = 0.04). In 2 patients from the group without G-CSF sepsis was diagnosed. G-CSF administration led to a shorter hospital stay: median 16 and 18 days in the 1st and 2nd groups, respectively (p = 0.08). There were no differences in the number of patients with febrile neutropenia.

Conclusion. G-CSF administration improves the course of the post-transplantation period in MM patients. The final decision on the feasibility of G-CSF administration after auto-HSCT can be made after more clinical observations are available.

Keywords: multiple myeloma, autologous hematopoietic stem cell transplantation, granulocyte colony-stimulating factor.

Received: January 14, 2020

Accepted: April 30, 2020

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REFERENCES

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  14. Грицаев С.В., Кострома И.И., Жернякова А.А. и др. Опыт применения режима кондиционирования Thio/Mel перед трансплантацией аутологичных гемопоэтических стволовых клеток при множественной миеломе. Клиническая онкогематология. 2019;12(3):282–8. doi: 10.21320/2500-2139-2019-12-3-282-288.[Gritsaev SV, Kostroma II, Zhernyakova AA, et al. Experience with the Use of Thio/Mel Conditioning Regimen Prior to Autologous Hematopoietic Stem Cell Transplantation in Multiple Myeloma. Clinical oncohematology. 2019;12(3):282–8. doi: 10.21320/2500-2139-2019-12-3-282-288. (In Russ)]

  15. Sato S, Tamai Y, Okada S, et al. Atraumatic splenic rupture due to ectopic extramedullary hematopoiesis after autologous stem cell transplantation in a patient with AL amyloidosis. Intern Med. 2018;57(3):399–402. doi: 10.2169/internalmedicine.9018-17.

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  19. Кострома И.И., Жернякова А.А., Чубукина Ж.В. и др. Заготовка гемопоэтических стволовых клеток у больных множественной миеломой: влияние предшествующей аутоТГСК терапии леналидомидом и режима мобилизации. Клиническая онкогематология. 2018;11(2):192–7. doi: 10.21320/2500-2139-2018-11-2-192-197.[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. (In Russ)]

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Safety and Efficacy of BeEAC as a Conditioning Regimen Prior to Autologous Hematopoietic Stem Cell Transplantation in Relapsed/Refractory Lymphomas

AUTOIMMUNE THROMBOCYTOPENIA , , ,

VO Sarzhevskii, AA Samoilova, VYa Melnichenko, YuN Dubinina, NE Mochkin, DS Kolesnikova, DA Fedorenko, EG Smirnova, AE Bannikova, VS Bogatyrev

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

For correspondence: Anastasiya Aleksandrovna Samoilova, 70 Nizhnyaya Pervomaiskaya str., Moscow, Russian Federation, 105203; Tel.: +7(495)603-72-17; e-mail: samoylove03@gmail.com

For citation: Sarzhevskii VO, Samoilova AA, Melnichenko VYa, et al. Safety and Efficacy of BeEAC as a Conditioning Regimen Prior to Autologous Hematopoietic Stem Cell Transplantation in Relapsed/Refractory Lymphomas. Clinical oncohematology. 2020;13(2):185–92 (In Russ).

DOI: 10.21320/2500-2139-2020-13-2-185-192

ABSTRACT

Aim. To assess the safety and efficacy of BeEAC as a conditioning regimen prior to autologous hematopoietic stem cell transplantation (auto-HSCT) in relapsed and primary resistant lymphomas (ClinicalTrials.gov NCT03315520).

Materials & Methods. The trial included 113 patients with Hodgkin’s (HL) and non-Hodgkin’s lymphomas (NHL). The patients were included into the protocol during the period from February 2016 to June 2018. Median follow-up was 26 months. Among the patients there were 58 men and 55 women. Median age was 33 years (range 18–65 years). In 72 patients HL and in 41 patients NHL (in 15 diffuse large B-cell lymphoma, in 8 primary mediastinal (thymic) large B-cell lymphoma, in 10 mantle cell lymphoma, in 4 peripheral T-cell lymphoma unspecified, and in 4 patients follicular lymphoma) were diagnosed. BeEAC conditioning regimen consisted of administering 160–200 mg/m2 bendamustine in increasing doses on Day –6 and Day –5 combined with fixed doses of 200 mg/m2 cytarabine every 12 hours, 200 mg/m2 etoposide, and 140 mg/kg cyclophosphamide from Day –4 to Day –1.

Results. In phase 1, when bendamustine dose was increased from 160 mg/m2 to 200 mg/m2, no dose-limiting toxicity was observed. Afterwards patients received 200 mg/m2 of bendamustine. The assessment of tumor status in 2–3 months after auto-HSCT showed that complete remission was achieved in 62.9 % (n = 71) of patients, partial remission in 16.8 % (n = 19) of patients, stabilization in 0.9 % (n = 1) of patients and progression in 15 % (n = 17) of patients. In 5 patients the treatment effect was not assessed. Early post-transplant mortality (up to Day +30) was 3.6 % (n = 4) and overall mortality within the follow-up period (median 26 months) was 23 % (n = 26). Overall survival in the whole cohort of patients for 12, 18, 24, and 36 months was 88 %, 82 %, 78 %, and 64 %, respectively, and progression-free survival was 61 %, 57 %, 54 %, and 40 %, respectively.

Conclusion. BeEAC proved to be relatively safe when applied as a conditioning regimen prior to auto-HSCT in HL and NHL patients. Further data need to be collected to finally assess the efficacy of this regimen and to conduct a retrospective comparative analysis of it and other conditioning regimens in lymphomas.

Keywords: high-dose chemotherapy, autologous hematopoietic stem cell transplantation, conditioning regimens, bendamustine, toxicity.

Received: September 6, 2019

Accepted: March 3, 2020

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  3. Damon LE, Johnson JL, Niedzwiecki D, et al. Immunochemotherapy and autologous stem-cell transplantation for untreated patients with mantle-cell lymphoma: CALGB 59909. J Clin Oncol. 2009;27(36):6101–8. doi: 10.1200/JCO.2009.22.2554.

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  6. Geisler CH, Kolstad A, Laurell A, et al. Nordic MCL2 trial update: six-year follow-up after intensive immunochemotherapy for untreated mantle cell lymphoma followed by BEAM or BEAC + autologous stem cell support: still very long survival but late relapses do occur. Br J Haemotol. 2012;158(3):355–62. doi: 10.1111/j.1365-2141.2012.09174.x.

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  8. Visani G, Malerba L, Stefani PM, et al. BeEAM (bendamustine, etoposide, cytarabine, melphalan) before autologous stem cell transplantation is safe and effective for resistant/relapsed lymphoma patients. Blood. 2011;118(12):3419–25. doi: 10.1182/blood-2011-04-351924.

  9. Chantepie SP, Garciaz S, Tchernonog E, et al. Bendamustine-based conditioning prior to autologous stem cell transplantation (ASCT): Results of a French multicenter study of 474 patients from LYmphoma Study Association (LYSA) centers. Am J Hematol. 2018;93(6):729–35. doi: 10.1002/ajh.25077.

  10. Carella AM, Santini G, Giordano D, et al. High-Dose Chemotherapy and Non-Frozen Autologous Bone Marrow transplantation in Relapsed Advanced Lymphomas or Those Resistant to Convential Chemotherapy. Cancer. 1984;54(12):2836–9. doi: 10.1002/1097-0142(19841215)54:12<2836::aid-cncr2820541203>3.0.co;2-r.

  11. Caballero MD, Rubio V, Rifon J, et al. BEAM chemotherapy followed by autologous stem cell support in lymphoma patients: analysis of efficacy, toxicity and prognostic factors. Bone Marrow Transplant. 1997;20(6):451–8. doi: 10.1038/sj.bmt.1700913.

  12. Jo JC, Kang BW, Jang G, et al. BEAC or BEAM high-dose chemotherapy followed by autologous stem cell transplantation in non-Hodgkin’s lymphoma patients: comparative analysis of efficacy and toxicity. Ann Hematol. 2008;87(1):43–8. doi: 10.1007/s00277-007-0360-0.

  13. Shi Y, Liu P, Zhou S, et al. Comparison of CBV, BEAM and BEAC high‐dose chemotherapy followed by autologous hematopoietic stem cell transplantation in non‐Hodgkin lymphoma: Efficacy and toxicity. Asia-Pacific J Clin Oncol. 2017;13(5):e423–e429. doi: 10.1111/ajco.12610.

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  15. Rauf MS, Maghfoor I, Elhassan TAM, Akhtar S. High-dose chemotherapy and auto-SCT for relapsed and refractory Hodgkin’s lymphoma patients refractory to first-line salvage chemotherapy but responsive to second-line salvage chemotherapy. Med Oncol. 2015;32(1):388. doi: 10.1007/s12032-014-0388-7.

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  17. Vose JM, Zhang MJ, Rowlings PA, et al. Autologous Transplantation for Diffuse Aggressive Non-Hodgkin’s Lymphoma in Patients Never Achieving Remission: A Report from the Autologous Blood and Marrow Transplant Registry. J Clin Oncol. 2001;19(2):406–13. doi: 10.1200/jco.2001.19.2.406.

Experience with the Use of Thio/Mel Conditioning Regimen Prior to Autologous Hematopoietic Stem Cell Transplantation in Multiple Myeloma

LYMPHOID TUMORS , , , ,

SV Gritsaev1, II Kostroma1, AA Zhernyakova1, IM Zapreeva1, EV Karyagina2, ZhV Chubukina1, SA Tiranova1, IS Martynkevich1, SS Bessmeltsev1, AV Chechetkin1

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

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

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

For citation: Gritsaev SV, Kostroma II, Zhernyakova AA, et al. Experience with the Use of Thio/Mel Conditioning Regimen Prior to Autologous Hematopoietic Stem Cell Transplantation in Multiple Myeloma. Clinical oncohematology. 2019;12(3):282–8 (In Russ).

doi: 10.21320/2500-2139-2019-12-3-282-288

ABSTRACT

Background. In multiple myeloma (MM) treatment a single autologous hematopoietic stem cell transplantation (auto-HSCT) is preceded by conditioning regimens aimed at intensifying cytoreductive effect. In the course of ongoing search for combined conditioning regimens an attractive option proved to be thiotepa/melphalan combination.

Aim. Data analysis of a pilot study of the efficacy of conditioning regimens including administration of two alkylating agents (thiotepa and melphalan) with subsequent auto-HSCT.

Materials & Methods. 9 patients received 10 auto-HSCTs with conditioning regimen including administration of 250 mg/m2 of thiotepa on Day –5 and 140 mg/m2 of melphalan on Day –2. After auto-HSCT pegylated filgrastim was administered in 8 patients. Engraftment period was calculated on the basis of absolute neutrophil count ≥ 0,5 × 109/L and thrombocyte level ≥ 20 × 109/L. Regimen toxicity was assessed according to CTCAE v5.0. Survival rates were estimated by Kaplan-Meier curves.

Results. The use of thiotepa did not require administration of any additional drugs. The incidence of mucositis and enteropathy of grade 1–2 was 100 % and 70 %, respectively. Pyrexia was reported in 7 auto-HSCTs. Pneumonia occurred in 1 patient. The infusion of 1–3 doses of platelet concentrate (median of 2 doses) was required in all patients except for one. Donor erythrocytes were transfused to 3 patients. Engraftment was reported in all patients within the period of 10–14 days. Median hospitalization duration from Day 0 to hospital discharge was 16 patient-days. After auto-HSCT the quality of response improved in 6 out of 9 patients. MM progression was reported in one patient with complex karyotype. Further follow-up showed progression in 2 patients. By December 2018 median follow-up of 9 patients from the date of auto-HSCT was 9 months (range 3–20 months), median progression-free survival was 17 months, median overall survival was not reached.

Conclusion. Acceptable toxicity, improvement of response quality, and maintenance of it for up to 20 months allow to consider combined conditioning regimen Thio/Mel to be a possible alternative to the standard Mel200 regimen.

Keywords: multiple myeloma, autologous hematopoietic stem cell transplantation, conditioning regimen, thiotepa, melphalan.

Received: December 26, 2018

Accepted: May 25, 2019

Read in PDF 

REFERENCES

  1. Бессмельцев С.С., Абдулкадыров К.М. Множественная миелома: руководство для врачей. М.: СИМК, 2016. 512 с.

    [Bessmeltsev SS, Abdulkadyrov KM. Mnozhestvennaya mieloma: rukovodstvo dlya vrachei. (Multiple myeloma: manual for physicians.) Moscow: SIMK Publ.; 2016. 512 p. (In Russ)]

  2. Менделеева Л.П., Вотякова О.М., Покровская О.С. и др. Национальные клинические рекомендации по диагностике и лечению множественной миеломы. Гематология и трансфузиология. 2016;61(1, прил. 2):1–24. doi: 10.18821/0234-5730-2016-61-1-S2-1-24.

    [Mendeleeva LP, Votyakova OM, Pokrovskaya OS, et al. National clinical guidelines on diagnosis and treatment of multiple myeloma. Gematologiya i transfuziologiya. 2016;61(1, Suppl 2):1–24. doi: 10.18821/0234-5730-2016-61-1-S2-1-24. (In Russ)]

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  4. Cavo M, Rajkumar SV, Palumbo A, et al. International Myeloma Working Group consensus approach to the treatment of multiple myeloma patients who are candidates for autologous stem cell transplantation. 2011;117(23):6063–73. doi: 10.1182/blood-2011-02-297325.

  5. Engelhardt M, Terpos E, Kleber M, et al. European Myeloma Network recommendations on the evaluation and treatment of newly diagnosed patients with multiple myeloma. Haematologica. 2014;99(2):232–42. doi: 10.3324/haematol.2013.099358.

  6. Sidiqi MH, Aljama MA, Bin Riaz I, et al. Bortezomib, lenalidomide, and dexamethasone (VRd) followed by autologous stem cell transplant for multiple myeloma. Blood Cancer J. 2018;8(8):106. doi: 10.1038/s41408-018-0147-7.

  7. Attal M, Lauwers-Cances V, Hulin C, et al. Lenalidomide, bortezomib, and dexamethasone with transplantation for myeloma. N Engl J Med. 2017;376(14):1311–20. doi: 10.1056/NEJMoa1611750.

  8. Attal M, Harousseau JL, Stoppa AM, et al. A prospective, randomized trial of autologous bone marrow transplantation and chemotherapy in multiple myeloma. Intergroupe Francais du Myelome. N Engl J Med. 1996;335(2):91–7.

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  10. Thoennissen GB, Gorlich D, Bacher U, et al. Autologous stem cell transplantation in multiple myeloma in the era of novel drug induction: a retrospective single-center analysis. Acta Haematol. 2017;137(3):163–72. doi: 10.1159/000463534.

  11. Ozaki S, Harada T, Saitoh T, et al. Survival of multiple myeloma patients aged 65–70 years in the era of novel agents and autologous stem cell transplantation. A multicenter retrospective collaborative study of the Japanese Society of Myeloma and the European Myeloma Network. Acta Haematol. 2014;132(2):211–9. doi: 10.1159/000357394.

  12. Cavo M, Salwender H, Rosinol L, et al. Double vs single autologous stem cell transplantation after bortezomib-based induction regimens for multiple myeloma: an integrated analysis of patient-level data from phase III European studies. Blood. 2013;122(21):767.

  13. Cavo M, Beksac M, Dimopoulos M, et al. Intensification therapy with bortezomib-melphalan-prednisone versus autologous stem cell transplantation for newly diagnosed multiple myeloma: an intergroup, multicenter, phase III study of the European Myeloma Network (EMN02/HO95 MM trial). 2016;128(22):673.

  14. Sonneveld P, Beksac M, van der Holt B, et al. Consolidation followed by maintenance therapy versus maintenance alone in newly diagnosed, transplant eligible patients with multiple myeloma (MM): a randomized phase 3 study of the European Myeloma Network (EMN02/HO95 MM Trial). 2016;128(22):242.

  15. Stadtmauer EA, Pasquini MC, Blackwell B, et al. Comparison of autologous hematopoietic cell transplant (autoHCT), bortezomib, lenalidomide and dexamethasone (RVD) consolidation with lenalidomide maintenance (ACM), tandem autoHCT with lenalidomide maintenance (TAM), and autoHCT with lenalidomide maintenance (AM) for upfront treatment of patients with multiple myeloma (MM): primary results from the randomized phase III trial of the Blood and Marrow Transplant Clinical Trials Network (BMT CTN 0702 – StaMINA Trial). 2016;128(22):LBA-1.

  16. Yhim HY, Kim K, Kim JS, et al. Matched-pair analysis to compare the outcomes of a second salvage auto-SCT to systemic chemotherapy alone in patients with multiple myeloma who relapsed after front-line auto-SCT. Bone Marrow Transplant. 2013;48(3):425–32. doi: 10.1038/bmt.2012.164.

  17. Olin RL, Vogl DT, Porter DL, et al. Second auto-SCT is safe and effective salvage therapy for relapsed multiple myeloma. Bone Marrow Transplant. 2009;43(5): 417–22. doi: 10.1038/bmt.2008.334.

  18. Abbi KKS, Zheng J, Devlin SM, et al. Second autologous stem cell transplant: an effective therapy for relapsed multiple myeloma. Biol Blood Marrow Transplant. 2015;21(3):468–72. doi: 10.1016/j.bbmt.2014.11.677.

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  33. Hari P, Reece DE, Randhawa J, et al. Final outcomes of escalated melphalan 280 mg/m2 with amifostine cytoprotection followed autologous hematopoietic stem cell transplantation for multiple myeloma: high CR and VGPR rates do not translate into improved survival. Bone Marrow Transplant. 2019;54(2):293–9. doi: 10.1038/s41409-018-0261-y.

  34. Auner HW, Iacobelli S, Sbianchi G, et al. Melphalan 140 mg/m2 or 200 mg/m2 for autologous transplantation in myeloma: results from the collaboration to collect autologous transplant outcomes in lymphoma and myeloma (CALM) study. A report by the EBMT Chronic Malignancies Working Party. Haematologica. 2018;103(3):514–21. doi: 10.3324/haematol.2017.181339.

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  36. Costa LJ, Landau HJ, Chhabra S, et al. Phase 1/2 trial of carfilzomib plus high-dose melphalan preparative regimen for salvage autologous hematopoietic cell transplantation followed by maintenance carfilzomib in patients with relapsed/refractory multiple myeloma. Biol Blood Marrow Transplant. 2018;24(7):1379–85. doi: 10.1016/j.bbmt.2018.01.036.

Factors Associated with Efficient Harvesting and Engraftment of Auto-Transplants in Multiple Myeloma Patients

BONE MARROW TRANSPLANTATION , , , ,

II Kostroma, AA Zhernyakova, ZhV Chubukina, NYu Semenova, IM Zapreeva, SA Tiranova, SS Bessmeltsev, 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; Tel.: +7(921)784-82-82; e-mail: obex@rambler.ru

For citation: Kostroma II, Zhernyakova AA, Chubukina ZhV, et al. Factors Associated with Efficient Harvesting and Engraftment of Auto-Transplants in Multiple Myeloma Patients. Clinical oncohematology. 2019;12(1):32–6.

DOI: 10.21320/2500-2139-2019-12-1-32-36

ABSTRACT

Background. The success of autologous hematopoietic stem cell transplantation (auto-HSCT) depends on the speed of transplant engraftment which in turn is affected by the count of harvested and infused hematopoietic stem cells (HSC).

Aim. To identify predictors of auto-HSCT efficacy in multiple myeloma (MM) patients under introduction of new drugs at the phase of HSC induction and mobilization.

Materials & Methods. The results of auto-transplant harvesting and engraftment were retrospectively analyzed in 75 MM patients during 112 auto-HSCTs. Auto-transplants were harvested using cyclophosphamide and vinorelbine combined with granulocyte colony-stimulating factor (G-CSF) without plerixafor. Conditioning regimen included melphalan 200 mg/m2 or 140 mg/m2, and combination of tiothepa with melphalan. All patients received subcutaneous injections of G-CSF in post-transplantation period. Transplant engraftment was assessed according to absolute neutrophil count of ≥ 0.5 × 109/L, and thrombocyte count of ≥ 20 × 109/L.

Results. It is established that the predictors of a high CD34+ cell count in auto-transplant are a single previous induction regimen (p = 0.0315) and administration of cyclophosphamide in mobilization regimen (р = 0.0001). Transplant engraftment period is determined by auto-HSCT serial number and amount of infused CD34+ cells. Hematopoiesis regeneration after the second auto-HSCT was accelerated by more frequent use of Mel140 (р = 0.001).

Conclusion. Auto-transplant quality and engraftment period in MM patients primarily depend on the efficacy of induction therapy and the intensity of HSC mobilization regimen. Therefore, induction therapy and mobilization regimen need to be tailored to an individual patient, MM prognostic variant, probability of response to standard induction regimens, and the number of planned auto-HSCTs.

Keywords: multiple myeloma, autologous hematopoietic stem cell transplantation, auto-HSCT efficacy predictors, transplant, engraftment.

Received: May 14, 2018

Accepted: December 2, 2018

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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

BONE MARROW TRANSPLANTATION , ,

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 (p = 0.4) nor ECOG status (p = 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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Autologous Hematopoietic Stem Cell Transplantation in Multiple Myeloma in the Era of New Drugs

BONE MARROW TRANSPLANTATION , ,

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 (p = 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 (p = 0.0016). MM relapse/progression occurred more frequently in the non-auto-HSCT treated patients (52.5 vs. 28.4 %; p = 0.0016). In multivariate analysis the age above 60 was determined as prognostic factor of lower PFS and increase in relapse/progression rate (p = 0.004 and p = 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 (p = 0.02 and p = 0.04, respectively). Complete nonresponsiveness to induction therapy has proved to be an independent predictor of both poor OS and PFS (p = 0.04 and p = 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 %; p = 0.03) and a decrease in relapse/progression frequency (26.1 vs. 32.1 %; p = 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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REFERENCES

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Certain Aspects of Autologous Hematopoietic Stem Cell Transplantation in Patients with Multiple Myeloma

REVIEWS , , ,

SV Gritsaev, AA Kuzyaeva, SS Bessmel’tsev

Russian Scientific Research Institute of Hematology and Transfusiology under the Federal Medico-Biological Agency, 16 2-ya Sovetskaya str., Saint Petersburg, Russian Federation, 191024

For correspondence: Sergei Vasil’evich Gritsaev, DSci, 16 2-ya Sovetskaya str., Saint Petersburg, Russian Federation, 191024; Tel: +7(812)717-58-57; e-mail: gritsaevsv@mail.ru

For citation: Gritsaev SV, Kuzyaeva AA, Bessmel’tsev SS. Certain Aspects of Autologous Hematopoietic Stem Cell Transplantation in Patients with Multiple Myeloma. Clinical oncohematology. 2017;10(1):7–12 (In Russ).

DOI: 10.21320/2500-2139-2017-10-1-7-12

ABSTRACT

The review dwells on certain problems of mobilization and conditioning regimens, as well as autologous hematopoietic stem cell transplantation (auto-HSCT) in patients with multiple myeloma. The aim of the review is to determine new approaches to improve the effectiveness of the auto-HSCT.

Keywords: multiple myeloma, autologous hematopoietic stem cell transplantation, mobilization regimen, conditioning regimen.

Received: July 13, 2016

Accepted: November 12, 2016

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