Correlation of CD34+ Hematopoietic Stem Cells and CFU in Peripheral Blood Apheresis Products in Patients with Malignant Lymphoproliferative Diseases Before and After Cryopreservation Prior to auto-HSCT

VA Balashova, VI Rugal’, SS Bessmel’tsev, SV Gritsaev, NYu Semenova, SV Voloshin, ZhV Chubukina, AV Shmidt, AD Garifullin, IM Zapreeva, AA Kuzyaeva, II Kostroma, AYu Kuvshinov, AV Chechetkin

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

For correspondence: Valentina Andreevna Balashova, MD, PhD, 16 2-ya Sovetskaya str., Saint Petersburg, Russian Federation, 191024; Tel.: +7(812)717-19-37; e-mail: vbspb37@mail.ru

For citation: Balashova VA, Rugal’ VI, Bessmel’tsev SS, et al. Correlation of CD34+ Hematopoietic Stem Cells and CFU in Peripheral Blood Apheresis Products in Patients with Malignant Lymphoproliferative Diseases Before and After Cryopreservation Prior to auto-HSCT. Clinical oncohematology. 2018;11(4):368–77.

DOI: 10.21320/2500-2139-2018-11-4-368-377


ABSTRACT

Aim. To establish correlation between CD34+ autologous hematopoietic stem cell (HSC) count and colony-forming units (CFU) in the same peripheral blood apheresis product samples before and after cryopreservation in multiple myeloma and lymphoma patients, and to assess clinical value of these parameters.

Materials & Methods. Cell samples of peripheral blood cytapheresis product and cell cultures were studied before and after cryopreservation in 32 multiple myeloma and 25 lymphoma patients who underwent autologous HSC transplantation. The material was analyzed using culture technique and flow cytometry.

Results. The paper provides information on the relationship between CD34+ HSC count obtained by flow cytometry, and CFU in cell culture obtained by cytapheresis of the same peripheral blood samples. A direct correlation was confirmed between CD34+ count and all the CFUs before and after cryopreservation in lymphoma patients. Correlation between CD34+ count and granulocyte-macrophage CFUs was revealed in multiple myeloma and lymphoma patients before cryopreservation.

Conclusion. The parameter of colony-forming capacity used for the assessment of the functional HSC was shown to be equally reliable criterion for condition evaluation of autotransplant proliferative pool than CD34+ cells. Both methods should be applied for qualitative and quantitative evaluation of an autotransplant for multiple myeloma and lymphoma patients.

Keywords: CD34+ cells, CFU, CFU-GM, correlation, lymphoma, multiple myeloma, apheresis, auto-HSCT.

Received: April 11, 2018

Accepted: July 28, 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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  30. Pusic I, Jiang SY, Landua S, et al. Impact of mobilization and remobilization strategies on achieving sufficient stem cell yields for autologous transplantation. Biol Blood Marrow Transplant. 2008;14(9):1045–56. doi: 1016/j.bbmt.2008.07.004.
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  33. Fruehauf S, Ehninger G, Hubel K, et al. Mobilization of peripheral blood stem cells for autologous transplant in non-Hodgkin’s lymphoma and multiple myeloma patients by plerixafor and G-CSF and detection of tumor cell mobilization by PCR in multiple myeloma patients. Bone Marrow Transplant. 2010;45(2):269–75. doi: 1038/bmt.2009.142.

Evolution of Anti-Cancer Treatment and its Impact on Surrogate Prognostic Factors in Multiple Myeloma

AS Luchinin1, SV Semochkin2, NV Minaeva1, NM Pozdeev1, IV Paramonov1

1 Kirov Research Institute of Hematology and Transfusiology, 72 Krasnoarmeiskaya str., Kirov, Russian Federation, 610027

2 NI Pirogov Russian National Research Medical University, 1 Ostrovityanova str., Moscow, Russian Federation, 117997

For correspondence: Aleksandr Sergeevich Luchinin, 72 Krasnoarmeiskaya str., Kirov, Russian Federation, 610027; Tel.: +7(919)506-87-86; e-mail: glivec@mail.ru

For citation: Luchinin AS, Semochkin SV, Minaeva NV, et al. Evolution of Anti-Cancer Treatment and its Impact on Surrogate Prognostic Factors in Multiple Myeloma. Clinical oncohematology. 2018;11(2):175–81.

DOI: 10.21320/2500-2139-2018-11-2-175-181


ABSTRACT

Aim. To assess prognostic value of surrogate clinical and laboratory markers in current therapy of multiple myeloma (MM).

Materials & Methods. The analysis included 567 patients (215 men and 352 women), the Kirov region inhabitants with newly diagnosed MM over the period from January 1, 1994 to December 31, 2016. The median age was 64 years (range 29–90). Patients were divided into two groups: the first group received treatment from 1994 to 2005 (n = 269), the second group received treatment from 2006 to 2016 (n = 298). Impact of factors on overall survival (OS) was evaluated by multivariate logistic regression analysis using the Cox method.

Results. Over the period from 2006 to 2016 the number of patients treated with traditional chemotherapy decreased from 78.4 to 32.5 %. At the same time the number of patients treated with bortezomib-based regimens increased from 1.9 to 56.3 % and autologous hematopoietic stem cell transplantation (auto-HSCT) protocols — from 1.4 to 14.0 %. Median OS over the period from 1994 to 2005 was 27 months. It increased to 55 months in the period of 2006–2016. In the reference decades 5-year overall survival increased from 21 % (95% confidence interval [95% CI] 17–27 %) to 47 % (95% CI 39–55 %), respectively (hazard ratio [HR] 0.51; 95% CI 0.41–0.64; < 0,0001). In patients treated with bortezomib-based regimens over the period from 2006 to 2016 median OS increased to 73 months compared to 27 months in 1994–2005. In patients aged ≤ 65 years and treated with auto-HSCT median OS was not reached, and median OS in patients without auto-HSCT treatment was 54 months.

Conclusions. Surrogate prognostic markers, such as the age over 65, hemoglobin level < 100 g/L, β2-microglobulin ≥ 6 mg/L, serum creatinine ≥ 177 µmol/L and stage III according to ISS and Durie-Salmon, are unfavourable predictors of survival of MM patients.

Keywords: multiple myeloma, prognosis, bortezomib, auto-HSCT, overall survival.

Received: December 21, 2017

Accepted: February 25, 2018

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REFERENCES

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Role of Positron-Emission Tomography in Prognosis of Outcomes of High-Dose Chemotherapy with Autologous Hematopoietic Stem Cell Transplantation in Hodgkin’s Lymphoma

VG Potapenko1,2, NB Mikhailova1, BI Smirnov4, IA Skorokhod2, DA Chaginskaya2, VV Ryabchikova2, IA Samorodova2, EI Podol’tseva2, VV Ipatov3, IV Boikov3, VN Semelev3, DA Gornostaev3, TG Potapenko5, TG Kulibaba5, NV Medvedeva2, BV Afanas’ev1

1 Academician IP Pavlov First St. Petersburg State Medical University, 6/8 L’va Tolstogo str., Saint Petersburg, Russian Federation, 197022

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

3 SM Kirov Military Medical Academy, 6 Akademika Lebedeva str., Saint Petersburg, Russian Federation, 194044

4 VI Ul’yanov (Lenin) St. Petersburg State Electrotechnical University LETI, 5 Professora Popova str., Saint Petersburg, Russian Federation, 197376

5 St. Petersburg State University, 7/9 Universitetskaya nab., Saint Petersburg, Russian Federation, 199034

For correspondence: Vsevolod Gennad’evich Potapenko, 6/8 L’va Tolstogo str., Saint Petersburg, Russian Federation, 197022; Tel: +7(812)230-19-33; е-mail: potapenko.vsevolod@mail.ru

For citation: Potapenko VG, Mikhailova NB, Smirnov BI, et al. Role of Positron-Emission Tomography in Prognosis of Outcomes of High-Dose Chemotherapy with Autologous Hematopoietic Stem Cell Transplantation in Hodgkin’s Lymphoma. Clinical oncohematology. 2016;9(4):406–12 (In Russ).

DOI: 10.21320/2500-2139-2016-9-4-406-412


ABSTRACT

Aim. To perform a comparative analysis of the prognostic significance of positron-emission tomography (PET) with other prognostic factors of the efficacy of high-dose chemotherapy (HDCT) with autologous hematopoietic stem cell transplantation (auto-HSCT) in patients with Hodgkin’s lymphoma.

Methods. Data on 84 patients with Hodgkin’s lymphoma receiving treatment over the period from October 2007 till November 2015 were analyzed. The median age was 26.6 years (range: 10–62). The median follow-up was 25 months (range: 1–81 months). The prognostic significance of sex, response to the initial chemotherapy, time to relapse, second-line chemotherapy regimen type, B-symptoms, tumor size (>5 cm in cases of relapse prior to the HDCT), serum LDH and albumin levels, CT findings, the number of chemotherapy lines, conditioning regimen before the auto-HSCT, and the metabolic activity before the HDCT (PET1, n = 82) and after auto-HSCT (PET2, n = 57) was analyzed.

Results. The two-year overall (OS) and event-free (EFS) survival rates were 70.6 % and 58.7%, respectively. Prognosis was the worst in patients with CT-confirmed lymphoma progression by the initiation of HDCT. In the presence of a CT-response, the PET status of lymphoma has a prognostic significance. The 2-year OS and EFS rates of PET1-negative and PET1-positive patients were 82 % vs. 62 % (= 0.056) and 74 % vs. 44 % (= 0.003), respectively. In PET2-negative and PET2-positive patients, the OS and EFS rates were 90 % vs. 65 % (= 0.013) and 72 % vs. 52 % (= 0.014), respectively. From the prognostic point of view, PET2 findings prevailed over PET1 findings. The multivariate analysis confirmed only PET2 significance for OS prediction.

Conclusion. The tumor sensitivity to the chemotherapy assessed by the CT is the most important prognostic factor. In case of a positive CT dynamics, the achievement of PET1 or PET2 negativity before or after HDCT/auto-HSCT is a favorable prognostic factor. The worst prognosis was observed in patients with tumor metabolic activity before or after HDCT/auto-HSCT.


Keywords: positron-emission tomography (PET), Hodgkin’s lymphoma, high-dose chemotherapy, auto-HSCT.

Received: June 23, 2016

Accepted: August 29, 2016

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Role of Positron-Emission Tomography in Prognosis of Outcomes of High-Dose Chemotherapy with Autologous Hematopoietic Stem Cell Transplantation in Hodgkin’s Lymphoma

VG Potapenko1,2, NB Mikhailova1, BI Smirnov4, IA Skorokhod2, DA Chaginskaya2, VV Ryabchikova2, IA Samorodova2, EI Podol’tseva2, VV Ipatov3, IV Boikov3, VN Semelev3, DA Gornostaev3, TG Potapenko5, TG Kulibaba5, NV Medvedeva2, BV Afanas’ev1

1 Academician IP Pavlov First St. Petersburg State Medical University, 6/8 L’va Tolstogo str., Saint Petersburg, Russian Federation, 197022

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

3 SM Kirov Military Medical Academy, 6 Akademika Lebedeva str., Saint Petersburg, Russian Federation, 194044

4 VI Ul’yanov (Lenin) St. Petersburg State Electrotechnical University LETI, 5 Professora Popova str., Saint Petersburg, Russian Federation, 197376

5 St. Petersburg State University, 7/9 Universitetskaya nab., Saint Petersburg, Russian Federation, 199034

For correspondence: Vsevolod Gennad’evich Potapenko, 6/8 L’va Tolstogo str., Saint Petersburg, Russian Federation, 197022; Tel: +7(812)230-19-33; е-mail: potapenko.vsevolod@mail.ru

For citation: Potapenko VG, Mikhailova NB, Smirnov BI, et al. Role of Positron-Emission Tomography in Prognosis of Outcomes of High-Dose Chemotherapy with Autologous Hematopoietic Stem Cell Transplantation in Hodgkin’s Lymphoma. Clinical oncohematology. 2016;9(4):406–12 (In Russ).

DOI: http://dx.doi.org/10.21320/2500-2139-2016-9-4-406-412


ABSTRACT

Aim. To perform a comparative analysis of the prognostic significance of positron-emission tomography (PET) with other prognostic factors of the efficacy of high-dose chemotherapy (HDCT) with autologous hematopoietic stem cell transplantation (auto-HSCT) in patients with Hodgkin’s lymphoma.

Methods. Data on 84 patients with Hodgkin’s lymphoma receiving treatment over the period from October 2007 till November 2015 were analyzed. The median age was 26.6 years (range: 10–62). The median follow-up was 25 months (range: 1–81 months). The prognostic significance of sex, response to the initial chemotherapy, time to relapse, second-line chemotherapy regimen type, B-symptoms, tumor size (>5 cm in cases of relapse prior to the HDCT), serum LDH and albumin levels, CT findings, the number of chemotherapy lines, conditioning regimen before the auto-HSCT, and the metabolic activity before the HDCT (PET1, n = 82) and after auto-HSCT (PET2, n = 57) was analyzed.

Results. The two-year overall (OS) and event-free (EFS) survival rates were 70.6 % and 58.7%, respectively. Prognosis was the worst in patients with CT-confirmed lymphoma progression by the initiation of HDCT. In the presence of a CT-response, the PET status of lymphoma has a prognostic significance. The 2-year OS and EFS rates of PET1-negative and PET1-positive patients were 82 % vs. 62 % (= 0.056) and 74 % vs. 44 % (= 0.003), respectively. In PET2-negative and PET2-positive patients, the OS and EFS rates were 90 % vs. 65 % (= 0.013) and 72 % vs. 52 % (= 0.014), respectively. From the prognostic point of view, PET2 findings prevailed over PET1 findings. The multivariate analysis confirmed only PET2 significance for OS prediction.

Conclusion. The tumor sensitivity to the chemotherapy assessed by the CT is the most important prognostic factor. In case of a positive CT dynamics, the achievement of PET1 or PET2 negativity before or after HDCT/auto-HSCT is a favorable prognostic factor. The worst prognosis was observed in patients with tumor metabolic activity before or after HDCT/auto-HSCT.

Keywords: positron-emission tomography (PET), Hodgkin’s lymphoma, high-dose chemotherapy, auto-HSCT.

Received: June 23, 2016

Accepted: August 29, 2016

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Treatment of Relapsed and Refractory Hodgkin’s Lymphoma in Children

NS Kulichkina, ES Belyaeva, GL Mentkevich, VK Boyarshinov, AS Levashov, IV Glekov, AV Popa

Scientific Research Institute of Pediatric Oncology and Hematology, N.N. Blokhin Russian Cancer Research Center, 24 Kashirskoye sh., Moscow, Russian Federation, 115478

For correspondence: Aleksandr Valentinovich Popa, DSci, 24 Kashirskoye sh., Moscow, Russian Federation, 115478; Tel.: +7(499)324-55-03; e-mail: apopa@list.ru

For citation: Kulichkina NS, Belyaeva ES, Mentkevich GL, et al. Treatment of Relapsed and Refractory Hodgkin’s Lymphoma in Children. Clinical oncohematology. 2016;9(1):13–21 (In Russ).

DOI: 10.21320/2500-2139-2016-9-1-13-21


ABSTRACT

Background & Aims. Most children with Hodgkin’s lymphoma (HL) can be cured irrespective of the disease stage using modern risk adapted protocols. But 3–5 % of children develop relapse of the disease or refractoriness to the treatment performed. The aim of the study was to perform a comparative analysis of ViGePP vs ICE antitumor treatment regimens in patients with relapsed and refractory Hodgkin’s lymphoma, as well as to evaluate the need in auto-HSCT and the site for a combined chemoradiation therapy in this patient population.

Methods. From June, 2003, till December, 2014, 35 patients with relapsed (18) and refractory (17) HL received chemotherapy based on two regimes: ICE (n = 14; 40 %) and ViGePP (n = 14; 40 %). 7 (20 %) children were switched to another regimen due to a poor antitumor response to the first two courses of chemotherapy.

Results. The direct effectiveness of the therapy was significantly higher in patients on ViGePP as compared to ICE irrespective of the disease status (relapsed or refractory). A complete response was achieved more often in those children with relapse HL whose initial treatment included radiation therapy. Higher survival rates were registered in girls, as well as in children with a complete overall response to the antirelapse therapy. In case of relapses, delayed treatment effects (disease free survival and overall survival) were higher in children treated with 4 courses of ViGePP than 2 courses of ICE. High-dose chemotherapy with subsequent auto-HSCT is not able to overcome refractoriness to the chemotherapy.

Conclusion. Children with relapsed and refractory HL need an intensive antirelapse chemotherapy with subsequent HDC and auto-HSCT to achieve CR.


Keywords: Hodgkin’s lymphoma, children, relapse, refractoriness, auto-HSCT.

Received: November 9, 2015

Accepted: December 25, 2015

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