Stable Chronology of Granulopoiesis under R(G)-DHAP Immunochemotherapy-Induced Cytotoxic Stress in Non-Hodgkin’s Lymphomas

In memory of Academician A.I. Vorob’ev,
Russian Academy of Medical Sciences and Russian Academy of Sciences

KA Sychevskaya, SK Kravchenko, FE Babaeva, AE Misyurina, AM Kremenetskaya, AI Vorob’ev

National Research Center for Hematology, 4 Novyi Zykovskii pr-d, Moscow, Russian Federation, 125167

For correspondence: Kseniya Andreevna Sychevskaya, 4 Novyi Zykovskii pr-d, Moscow, Russian Federation, 125167; Tel.: +7(910)409-79-44; e-mail: sychevskaya-ka@yandex.ru

For citation: Sychevskaya KA, Kravchenko SK, Babaeva FE, et al. Stable Chronology of Granulopoiesis under R(G)-DHAP Immunochemotherapy-Induced Cytotoxic Stress in Non-Hodgkin’s Lymphomas. Clinical oncohematology. 2021;14(2):204–19. (In Russ).

DOI: 10.21320/2500-2139-2021-14-2-204-219


ABSTRACT

Background. Chronology of granulopoiesis based on periodic hematopoiesis model has been thoroughly studied. However, the pattern of influence of chemotherapy- and immunotherapy-induced cytotoxic stress on the development rhythm of a stem cell requires further investigation. The interaction of antitumor drugs with normal hematopoietic cells is relevant for assessing the intensity of chemotherapy adverse events. Besides, there is a demand for studying hematopoiesis under cytotoxic stress to predict immunological reactivity as a condition for efficacy of immunotherapeutic agents, the effect of which is based on cell immunity.

Aim. To study the chronological pattern of leukocyte count dynamics after R(G)-DHAP immunochemotherapy in non-Hodgkin’s lymphomas.

Materials & Methods. The dynamics of leukocyte count changes after R(G)-DHAP immunochemotherapy was analyzed using the data of 39 treatment courses in 19 non-Hodgkin’s lymphomas patients. After 18 out of 39 cycles of treatment granulocyte colony-stimulating factor (G-CSF) was administered to prevent granulocytopenia, in other cases the previously planned hematopoietic stem cell mobilization was performed according to the accepted protocol.

Results. Time to activation of spontaneous granulopoiesis depends neither on G-CSF stimulation, nor on the total dose of growth-stimulating factor and corresponds on average to Day 10 or Day 11 of the break from the last day of immunochemotherapy. The tendency of shorter agranulocytosis duration on prophylactic use of G-CSF is associated with transient hyperleukocytosis at an early stage after completing immunochemotherapy. Regimens with platinum-based drugs, like R(G)-DHAP, are suggested to be combined with immunochemotherapeutic agents in patients with the failure of first-line chemotherapy. The time interval preceding myelopoiesis activation within the first days of the break between the courses is likely to contribute to the initiation of treatment with immunotherapeutic drugs after second-line chemotherapy.

Conclusion. The determination of granulopoiesis dynamics under R(G)-DHAP immunochemotherapy-induced cytotoxic stress enables to plan the optimum G-CSF regimen and to predict the optimum timing of immune antitumor effect combined with chemotherapy.

Keywords: periodic hematopoiesis, mathematical hematopoiesis model, non-Hodgkin’s lymphomas, chemotherapy, immunotherapy, G-CSF, antitumor immunity, R(G)-DHAP.

Received: November 15, 2020

Accepted: February 25, 2021

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Plerixafor in Patients with Decreased Mobilizing Ability of Autologous Hematopoietic Stem Cells

MA Kucher1, МS Motalkina2, ОU Klimova1, ЕV Kondakova1, ОB Kalashnikova1, SМ Alekseev2, DV Motorin3, DV Babenetskaya3, EI Podoltseva4, NB Mikhailova1, МА Estrina1, ЕV Babenko1, AYu Zaritskii3, BV Afanasev1

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

2 N.N. Petrov Scientific Research Institute of Oncology, 68 Leningradskaya str., settlement Pesochnyi, Saint Petersburg, Russian Federation, 197758

3 V.A. Almazov Federal North-West Medical Research Centre, 2 Akkuratova str., Saint Petersburg, Russian Federation, 197341

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

For correspondence: Maksim Anatol’evich Kucher, PhD, 6/8 L’va Tolstogo str., Saint Petersburg, Russian Federation, 197022; Tel.: +7(812)338-62-60; e-mail: doctorkucher@yandex.ru

For citation: Kucher MA, Motalkina MS, Klimova OU, et al. Plerixafor in Patients with Decreased Mobilizing Ability of Autologous Hematopoietic Stem Cells. Clinical oncohematology. 2016;9(2):155–61 (In Russ).

DOI: 10.21320/2500-2139-2016-9-2-155-161


ABSTRACT

Background & Aims. Autologous hematopoietic stem cell transplantation (autoHSCT) is an effective treatment for patients with malignant lymphoproliferative disorders, multiple myelomas and solid tumors sensitive to chemotherapy. Harvesting of hematopoietic stem cells (HSC) prior autoHSCT may be ineffective in up to 40 % of cases, if aggravating factors are present. One of methods to overcome the reduced mobilization ability is to include a CXCR4-inhibitor (plerixafor) to the mobilization strategies. The aim was to evaluate the efficacy and safety of different autologous HSC mobilization regimens containing plerixafor.

Methods. 63 patients with solid and hematological malignancies were included into the study. 2 mobilization regimens were used: filgrastim + plerixafor (n = 47) and pegfilgrastim + plerixafor (n = 16). Filgrastim was prescribed at a dose 5 mg/kg twice a day subcutaneously on days 1–4; on day 4, at 12.00 am, plerixafor was prescribed at a dose of 0.24 mg/kg subcutaneously; on day 5, filgrastim 5 mg/kg was administered subcutaneously, and then a cytapheresis session was performed at 10.00 am. Pegfilgrastim was administered subcutaneously at a dose of 6 mg on day 1; on day 4, plerixafor was administered subcutaneously at a dose of 0.24 mg/kg at 06.00 am; then, 11 hours later, cytapheresis was performed. The cytapheresis was performed at a level of CD34+ cells ³ 20 ´ 106/mL.

Results. In 73.7 % of cases (n = 42), patients had an advanced stage disease and underwent more than one chemotherapy line prior to mobilization of autologous HSC. After mobilization with G-CSF (filgrastim or pegfilgrastim), the CD34+ cell count in peripheral blood was 0–17 ´ 106/mL (median 9.8 ´ 106/mL). Further injection of plerixafor increased the CD34+ cell count to 2–89 ´ 106/mL (median 31.6 ´ 106/mL) (= 0.0001). In 85.7 % of cases (n = 54), the sufficient amount of CD34+ cells (³ 2 ´ 106/kg; median 5.1 ´ 106/kg) was harvested for transplantation. The effectiveness of mobilization in two groups was comparable 90.2 % for the filgrastim + plerixafor regimen and 68.7 % for pegfilgrastim + plerixafor (= 0.08). The use of the filgrastim + plerixafor combination in patients with low baseline CD34+ cell counts increased the number of hematopoietic stem cells up to 6.6–63 ´ 106/mL (median 27.1 ´ 106/mL), thus allowing to harvest a good quality graft in 83.3 % of cases (= 0.0001). When the level of CD34+ cell counts was in the «grey zone», successful graft harvesting was performed in 90 % of cases: 1.74–4.6 ´ 106/kg; median 3.1 ´ 106/kg (= 0.0001). Complications associated with plerixafor were observed in 2 cases: diarrhea (n = 1) and hypocalcaemia (n = 1).

Conclusion. In patients who are poor mobilizers, the use of plerixafor-containing regimens increased the chance of successful graft harvesting with good tolerability.


Keywords: hematopoietic stem cell mobilization, G-CSF, pegfilgrastim, plerixafor.

Received: February 17, 2016

Accepted: February 18, 2016

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