Plerixafor: A chemokine receptor-4 antagonist for mobilization of hematopoietic stem cells for transplantation after high-dose chemotherapy for non-hodgkin's lymphoma or multiple myeloma

Background: High-dose chemotherapy (HDCT) followed by autologous transplantation of hematopoietic stem cells (auto-HSCT) is an important component of treatment in multiple myeloma (MM). There is a standard method of controlled cryopreservation of HSC suspension. We found that the storage of native HSC suspension with temperature fluctuations from +3 °C to +5 °C during 72 - 120 hours does not significantly affect the content of CD34+ cells in the product, the index 7AAD- (7-AAD (7-aminoactinomycin - D) is a fluorescent marker that penetrates damaged cell membranes and binds to double-stranded DNA. Through 7AAD does not penetrate intact membranes, so living cells are not stained 7AAD with flow cytometry), and colony-forming ability (CFA) of HSC, as well as the recovery time of hematopoiesis in MM patients after auto-HSCT. Aim: To evaluate the effectiveness and safety of the method of storage of non-cryopreserved peripheral blood stem cells. Methods: 39 patients with MM were included in this study(male/female ratio 1.36:1). All the patients get standard immunochemotherapy programs and were in remission at the time of auto-HSCT. Patients were divided into two groups depending on the method of stem cell storage: group 1 - non-cryopreserved (n=20), group 2 - cryopreserved (standard) (n=19). An effectivity and safety were evaluated in such parameters as the number of CD34+ and 7AAD- cells, CFA after apheresis and before reinfusion of HSC. Also, we evaluated the number of platelets concentrate transfusions, the timing of engraftment of granulocytic and megakaryocytic blood sprouts, the length of hospital stays after auto-HSCT. Results: The results are presented in the comparison table of the evaluated parameters. Our data showed significantly reduce of episodes febrile neutropenia and cases of enteropathy. Conclusion: Thus, the proposed method of storage of HSC is not inferior to the traditional method with cryopreservation on such parameters as CD34+, 7AAD-, CFA, the number of platelets concentrate transfusions, terms of hematopoiesis restoration, length of hospital stay after HSCT, the number of complications. Table. Disclosures Shuvaev: Fusion Pharma: Consultancy; BMS: Consultancy; Novartis: Consultancy; Pfize: Honoraria.

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Optimization of methods for collecting peripheral hematopoietic stem cells in children with cancer: literature review

Russian Journal of Pediatric Hematology and Oncology ◽

10.21682/2311-1267-2020-7-2-78-85 ◽

2020 ◽

Vol 7 (2) ◽

pp. 78-85

Author(s):

N. G. Stepanyan ◽

N. V. Sidorova ◽

M. V. Rubanskaya ◽

N. N. Tupitsyn ◽

N. V. Matinyan ◽

...

Keyword(s):

Stem Cells ◽

Hematopoietic Stem Cells ◽

High Dose Chemotherapy ◽

Optimal Number ◽

High Dose ◽

Hematopoietic Stem ◽

Cd34 Cells ◽

Cxcr4 Antagonists ◽

Somatic State ◽

Stimulating Factor

Autologous hematopoietic stem cell transplantation (auto-HSCT) is a standard for the treatment of oncological, hematologic, and also some immune diseases, ensuring the restoration of blood counts after high-dose chemotherapy. In children, the success of mobilization and collection of hematopoietic stem cells (HSCs) is especially important. Mobilization schemes for children are decided on an individual basis, which requires the development and implementation of recommendations for improving the efficiency of mobilization and collection of HSCs. Mobilization schemes include the use of granulocyte colony-stimulating factor in the form of monotherapy or in combination with CXCR4 antagonists. These schemes are ineffective in some children, which requires re-mobilization or rejection of transplantation, which negatively affects the prognosis. When preparing a patient for HSCs collection, it is necessary to take into account all previous therapy, the patient’s age, weight and height indicators, and general somatic state. Harvesting the required amount of HSCs will allow for high-dose therapy followed by auto-HSCT, and thereby increase the effectiveness of treatment. It is necessary to optimize the protocol for mobilization of HSCs with a large bias for pediatric patients, which will clearly define the criteria for mobilization, give indications for this procedure and determine the criteria for technical collection, which will allow to obtain the optimal number of CD34+ cells, which will ensure the success of the treatment.

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THE ROLE OF SUBPOPULATIONS OF MOBILIZED PERIPHERAL HEMATOPOIETIC STEM CELLS IN THE RESTORATION OF HEMATOPOIESIS DURING HIGH-DOSE CHEMOTHERAPY IN CANCER PATIENTS

Hematology Transfusion and Cell Therapy ◽

10.1016/j.htct.2021.10.1049 ◽

2021 ◽

Vol 43 ◽

pp. S47-S48

Author(s):

Liudmila GRIVTSOVA ◽

Nikolai TUPITSYN

Keyword(s):

Stem Cells ◽

Hematopoietic Stem Cells ◽

Cancer Patients ◽

High Dose Chemotherapy ◽

High Dose ◽

Hematopoietic Stem

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Autografting Followed by Nonmyeloablative Immunosuppressive Chemotherapy and Allogeneic Peripheral-Blood Hematopoietic Stem-Cell Transplantation as Treatment of Resistant Hodgkin’s Disease and Non-Hodgkin’s Lymphoma

Journal of Clinical Oncology ◽

10.1200/jco.2000.18.23.3918 ◽

2000 ◽

Vol 18 (23) ◽

pp. 3918-3924 ◽

Cited By ~ 182

Author(s):

Angelo M. Carella ◽

Marina Cavaliere ◽

Enrica Lerma ◽

Raimondo Ferrara ◽

Lucilla Tedeschi ◽

...

Keyword(s):

Stem Cells ◽

Hodgkin's Disease ◽

Hodgkin’S Lymphoma ◽

Progressive Disease ◽

Hodgkin’S Disease ◽

Hodgkin's Lymphoma ◽

High Dose ◽

Hematopoietic Stem ◽

Non Hodgkin’S Lymphoma ◽

Non Hodgkin's Lymphoma

PURPOSE: To investigate the use of a nonmyeloablative fludarabine-based immunosuppressive regimen to allow engraftment of HLA-sibling donors’ mobilized stem cells and induction of a graft-versus-lymphoma effect for patients with advanced resistant Hodgkin’s disease and non-Hodgkin’s lymphoma. PATIENTS AND METHODS: Fifteen patients with Hodgkin’s disease (n = 10) and non-Hodgkin’s lymphoma (n = 5) were studied. All patients received cyclophosphamide and granulocyte colony-stimulating factor to mobilize autologous hematopoietic stem cells (HSCs). Subsequently, they received high-dose therapy with carmustine, etoposide, cytarabine, and melphalan and reinfusion of HSCs. At a median of 61 days after engraftment, patients were given fludarabine 30 mg/m2 with cyclophosphamide 300 mg/m2 daily for 3 days. Donor-mobilized HSC collections were prepared for fresh infusion and were not T-cell depleted. Methotrexate and cyclosporine were used to prevent graft rejection and as graft-versus-host disease (GVHD) prophylaxis. RESULTS: Combined treatment was well tolerated. After mini-allografting, hematologic recovery was prompt. Thirteen patients had 100% donor cell engraftment. Eleven patients achieved complete remission (CR) after the combined procedure. Nine patients, who were in partial remission after autografting, achieved CR after mini-allografting. Seven patients developed ≥ grade 2 acute GVHD (aGVHD) and two developed extensive chronic GVHD (cGVHD). Three patients who received the highest number of donor lymphocyte infusions (DLIs) developed grade 3 GVHD (two patients) and extensive cGVHD (one patient). Ten patients are currently alive, and five are in continuous CR. Seven patients received DLI, with five CRs. Five patients died: one of progressive disease, two of progressive disease combined with aGVHD or cGVHD, one of extensive cGVHD, and one of infection. CONCLUSION: Fludarabine/cyclophosphamide was well tolerated and allowed consistent engraftment in lymphoma allografted patients. Response rates were high in this group of refractory and heavily pretreated patients. This dual procedure seems to be most promising in patients with end-stage malignant lymphomas.

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