The role and place of high-dose immunosuppressive therapy and autologous transplantation of hematopoietic stem cells for autoimmune diseases

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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High-Dose Immune Suppression without Hematopoietic Stem Cells for Autoimmune Diseases

Stem Cell Therapy for Autoimmune Disease ◽

10.1201/9780367813895-28 ◽

2019 ◽

pp. 232-236

Author(s):

Robert A. Brodsky

Keyword(s):

Stem Cells ◽

Autoimmune Diseases ◽

Hematopoietic Stem Cells ◽

Immune Suppression ◽

High Dose ◽

Hematopoietic Stem

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Mobilization of Hematopoietic Stem Cells into Peripheral Blood for Autologous Transplantation Seems Less Efficacious in Poor Mobilizers with the Use of a Biosimilar of Filgrastim and Plerixafor: A Retrospective Comparative Analysis

Oncology and Therapy ◽

10.1007/s40487-020-00115-3 ◽

2020 ◽

Vol 8 (2) ◽

pp. 311-324

Author(s):

Rocío Parody ◽

Isabel Sánchez-Ortega ◽

Christelle Ferrá ◽

Ramon Guardia ◽

Carme Talarn ◽

...

Keyword(s):

Stem Cells ◽

Comparative Analysis ◽

Hematopoietic Stem Cells ◽

Peripheral Blood ◽

Autologous Transplantation ◽

Hematopoietic Stem ◽

Poor Mobilizers

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High-dose fractionated total-body irradiation, etoposide, and cyclophosphamide followed by autologous stem-cell support in patients with malignant lymphoma.

Journal of Clinical Oncology ◽

10.1200/jco.1994.12.12.2559 ◽

1994 ◽

Vol 12 (12) ◽

pp. 2559-2566 ◽

Cited By ~ 51

Author(s):

C H Weaver ◽

F B Petersen ◽

F R Appelbaum ◽

W I Bensinger ◽

O Press ◽

...

Keyword(s):

Stem Cells ◽

Stem Cell ◽

Hematopoietic Stem Cells ◽

Malignant Lymphoma ◽

Total Body Irradiation ◽

Advanced Disease ◽

High Dose ◽

Hematopoietic Stem ◽

Total Body ◽

M Estimates

PURPOSE To evaluate a high-dose treatment regimen of fractionated total-body irradiation (TBI), etoposide, and cyclophosphamide (Cy) followed by autologous stem-cell transplantation (ASCT) in patients with malignant lymphoma. PATIENTS AND METHODS Fifty-three patients with non-Hodgkin's lymphoma (NHL; n = 43) or Hodgkin's disease (HD; n = 10) received 12.0 Gy of fractionated TBI, etoposide 60 mg/kg, and Cy 100 mg/kg followed by infusion of autologous hematopoietic stem cells. RESULTS Thirty-one of 53 patients are alive a median of 643 (range, 177 to 1,144) days after transplant. The 2 year Kaplan-Meier (K-M) estimates of survival, event-free survival (EFS), and relapse for all 53 patients were 54%, 45%, and 43%, respectively. Sixteen of 24 patients with less advanced disease and 10 of 29 patients with more advanced disease survive free of disease for K-M estimates of EFS of 61% and 31%, respectively (P = .006). The K-M estimates of relapse were 34% for patients with less advanced disease and 53% (P = .05) for patients with more advanced disease. The K-M estimates of dying from causes other than relapse were 8% in patients with less versus 25% in patients with more advanced disease (P = .09). CONCLUSION These data indicate that approximately 60% of patients transplanted early after failure of initial therapy for malignant lymphoma are projected to be disease-free more than 2 years after treatment with fractionated TBI, etoposide, and Cy and infusion of autologous hematopoietic stem cells. The transplant-related mortality rate is low and relapse is the main cause of treatment failure in patients with less advanced disease. For patients with more advanced disease, the K-M estimates of both transplant-related deaths (25%) and relapse (53%) remain major problems.

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Cytopenia and autoimmune diseases: A vicious cycle fueled by mTOR dysregulation in hematopoietic stem cells

Journal of Autoimmunity ◽

10.1016/j.jaut.2012.12.011 ◽

2013 ◽

Vol 41 ◽

pp. 182-187 ◽

Cited By ~ 13

Author(s):

Pan Zheng ◽

Xing Chang ◽

Qianjin Lu ◽

Yang Liu

Keyword(s):

Stem Cells ◽

Autoimmune Diseases ◽

Hematopoietic Stem Cells ◽

Vicious Cycle ◽

Hematopoietic Stem

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Apheresis of peripheral blood stem cells in children with very low body weight: a single centre experience

Pediatric Hematology/Oncology and Immunopathology ◽

10.24287/1726-1708-2020-19-2-152-159 ◽

2020 ◽

Vol 19 (2) ◽

pp. 152-159

Author(s):

E. E. Kurnikova ◽

I. G. Khamin ◽

V. V. Shchukin ◽

T. V. Shamanskaya ◽

M. S. Fadeeva ◽

...

Keyword(s):

Stem Cells ◽

Body Weight ◽

Stem Cell ◽

Hematopoietic Stem Cells ◽

Hematopoietic Stem Cell ◽

Central Venous Access ◽

High Dose ◽

Term Survival ◽

Hematopoietic Stem ◽

Cd34 Cells

Polychemotherapy, accompanied by autologous hematopoietic stem cell transplantation, can improve the results of long-term survival of patients with cancer and some non-cancer diseases. Mobilizing and collecting hematopoietic stem cells in children with very low body weight can be a difficult task. The study was approved by the Independent Ethics Committee and the Scientific Council of the Dmitry Rogachev National Medical Research Center of Pediatric Hematology, Oncology, and Immunology. 19 children with extremely low body weight was included in the current study. The median age was 8 (5–14) months, the median of body weight 7.5 (5.8–8.8) kg. Apheresis was performed in an ICU, using sedative therapy and in compliance with the conditions for the prevention of anemia, hypovolemia, hypothermia. 19 hematopoietic stem cell apheresis were performed using the Spectra Optia MNC separator program. Mobilization of CD34+ cells was performed with filgrastim; three children were additionally given plerixaphor. All 19 hematopoietic stem cell apheresis were successful: the median of collected CD34+ cells was 18.7 × 106/kg (8.6– 60.6 × 106/kg), the median apheresis duration was 204 (161–351) min. Serious side effects during apheresis were not recorded, however, in 6 children (31%) we encountered difficulties in the process of installing central venous access. The collection of hematopoietic stem cells for the future high-dose chemotherapy with autologous hematopoietic stem cells is a feasible task even for very young children with extremely low body weight. Correct preparation for manipulation, taking into account all possible risk factors and technical features, can avoid serious complications.

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Differential mobilization of myeloma cells and normal hematopoietic stem cells in multiple myeloma after treatment with cyclophosphamide and granulocyte-macrophage colony-stimulating factor

Blood ◽

10.1182/blood.v87.2.805.bloodjournal872805 ◽

1996 ◽

Vol 87 (2) ◽

pp. 805-811 ◽

Cited By ~ 63

Author(s):

Y Gazitt ◽

E Tian ◽

B Barlogie ◽

CL Reading ◽

DH Vesole ◽

...

Keyword(s):

Stem Cells ◽

Hematopoietic Stem Cells ◽

High Dose ◽

Colony Stimulating Factor ◽

Hematopoietic Stem ◽

Myeloma Cells ◽

Cd34 Cells ◽

Macrophage Colony Stimulating Factor ◽

Macrophage Colony ◽

Stimulating Factor

Peripheral blood stem cells (PBSCs) mobilized with high-dose chemotherapy and hematopoietic growth factors are now widely used to support myeloablative therapy of multiple myeloma and effect complete remissions in up to 50% of patients with apparent extension of event- free and overall survival. Because tumor cells are present not only in bone marrow, but also in virtually all PBSC harvests, it is conceivable that autografted myeloma cells contribute to relapse after autotransplants. In this study, the kinetics of mobilization of normal hematopoietic stem cells were compared with those of myeloma cells present in PBSC harvests of 12 patients after high-dose cyclophosphamide and granulocyte-macrophage colony-stimulating factor administration. CD34+ and CD34+Lin-Thy+ stem cell contents were measured by multiparameter flow cytometry, and myeloma cells were quantitated by immunostaining for the relevant Ig light chain and by a quantitative polymerase chain reaction for the myeloma-specific CDRIII sequence. Results indicated marked heterogeneity in the percentages of mobilized stem cells among different patients (0.1% to 22.2% for CD34+ cells and 0.1% to 7.5% for CD34+Lin-Thy+ cells, respectively). The highest proportions of hematopoietic progenitor cells were observed early during apheresis, with 9 of 12 patients mobilizing adequate amounts of CD34+ cells for 2 autotransplants (> 4 x 10(6)/kg) within the first 2 days, whereas peak levels (percent and absolute numbers) of myeloma cells were present on days 5 and 6 (0.5% to 22.0%). During the last days of collection, mobilized tumor cells exhibited more frequently high labeling index values (1% to 10%; median, 4.4%) and an immature phenotype (CD19+). The differential mobilization observed between normal hematopoietic stem cells and myeloma cells can be exploited to reduce tumor cell contamination in PBSC harvests.

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