Efficacy and safety of VRD regimen of autologous hematopoietic stem cell transplantation in patients with newly diagnosed multiple myeloma / 中华内科杂志

Objective: To explore the stem cell collection rate and efficacy and safety of patients aged 70 and below with newly diagnosed multiple myeloma (MM) treated with the VRD (bortezomib, lenalidomide and dexamethasone) regimen followed by autologous stem cell transplantation (ASCT). Methods: Retrospective case series study. The clinical data of 123 patients with newly diagnosed MM from August 1, 2018, to June 30, 2020, at the First Affiliated Hospital of Soochow University and Suzhou Hopes Hematology Hospital, who were eligible for VRD regimen sequential ASCT, were collected. The clinical characteristics, efficacy after induction therapy, mobilization regimen of autologous stem cells, autologous stem cell collection rate, and side effects and efficacy of ASCT were retrospectively analyzed. Results: Of the 123 patients, 67 were males. The median patient age was 56 (range: 31-70) years. Patients with IgG, IgA, IgD, and light-chain types accounted for 47.2% (58/123), 23.6% (29/123), 3.2% (4/123), and 26.0% (32/123) of patients, respectively. In addition, 25.2% (31/123) of patients had renal insufficiency (creatinine clearance rate<40 ml/min). Patients with Revised-International Staging System (R-ISS) Ⅲ accounted for 18.2% (22/121) of patients. After induction therapy, the rates of partial response and above, very-good partial response (VGPR) and above, and complete response (CR)+stringent CR were 82.1% (101/123), 75.6% (93/123), and 45.5% (56/123), respectively. Overall, 90.3% (84/93) of patients were mobilized with cyclophosphamide+granulocyte colony-stimulating factor (G-CSF) and 8 patients with G-CSF or G-CSF+plerixafor due to creatinine clearance rate<30 ml/min and one of them was mobilized with DECP (cisplatin, etoposide, cyclophosphamide and dexamethasone)+G-CSF for progressive disease. The rate of autologous stem cell collection (CD34+cells≥2×106/kg) after four courses of VRD regimen was 89.1% (82/92), and the rate of collection (CD34+cells≥5×106/kg) was 56.5% (52/92). Seventy-seven patients treated with the VRD regimen sequential ASCT. All patients had grade 4 neutropenia and thrombocytopenia. Among the nonhematologic adverse events during ASCT, the highest incidence was observed for gastrointestinal reactions (76.6%, 59/77), followed by oral mucositis (46.8%, 36/77), elevated aminotransferases (44.2%, 34/77), fever (37.7%, 29/77), infection (16.9%, 13/77) and heart-related adverse events (11.7%, 9/77). Among the adverse events, grade 3 adverse events included nausea (6.5%, 5/77), oral mucositis (5.2%, 4/77), vomiting (3.9%, 3/77), infection (2.6%, 2/77), elevated blood pressure after infusion (2.6%, 2/77), elevated alanine transaminase (1.3%, 1/77), and perianal mucositis (1.3%, 1/77); there were no grade 4 or above nonhematologic adverse events. The proportion of patients who achieved VGPR and above after VRD sequential ASCT was 100% (75/75), and the proportion of patients who were minimal residual disease-negative (<10-4 level) was 82.7% (62/75). Conclusion: In patients aged 70 and below with newly diagnosed MM treated with VRD induction therapy, the collection rate of autologous stem cells was good, and good efficacy and tolerability were noted after follow-up ASCT.

Expression Changes of Hypoxia-Inducible Factor-1α in G-CSF Induced Hematopoietic Stem Cell Mobilization / 中国实验血液学杂志

OBJECTIVE@#To investigate the expression and its relative mechanism of hypoxia-inducible factor-1α(HIF-1α) in bone marrow(BM) of mice during G-CSF mobilization of hematopoietic stem cells (HSC) .@*METHODS@#Flow cytometry was used to detect the proportion of Lin-Sca-1+ c-kit+ (LSK) cells in peripheral blood of C57BL/6J mice before and after G-CSF mobilization. And the expression of HIF-1α and osteocalcin (OCN) mRNA and protein were detected by RQ-PCR and immunohistochemistry. The number of osteoblasts in bone marrow specimens of mice was counted under the microscope.@*RESULTS@#The proportion of LSK cells in peripheral blood began to increase at day 4 of G-CSF mobilization, and reached the peak at day 5, which was significantly higher than that of control group (P<0.05). There was no distinct difference in the expression of HIF-1α mRNA between bone marrow nucleated cells and osteoblasts of steady-state mice (P=0.073), while OCN mRNA was mainly expressed in osteoblasts, which was higher than that in bone marrow nucleated cells (P=0.034). After mobilization, the expression level of HIF-1α increased, but OCN decreased, and the number of endosteum osteoblasts decreased. The change of HIF-1α expression was later than that of OCN and was consistent with the proportion of LSK cells in peripheral blood.@*CONCLUSION@#The expression of HIF-1α in bone marrow was increased during the mobilization of HSC mediated by G-CSF, and one of the mechanisms may be related to the peripheral migration of HSC induced by osteoblasts inhibition.

Efficiency and safety analysis of Plerixafor combined with granulocyte colony-stimulating factor on autologous hematopoietic stem cell mobilization in lymphoma / 中华血液学杂志

Objective: To evaluate the advantages and safety of Plerixafor in combination with granulocyte colony-stimulating factor (G-CSF) in autologous hematopoietic stem cell mobilization of lymphoma. Methods: Lymphoma patients who received autologous hematopoietic stem cell mobilization with Plerixafor in combination with G-CSF or G-CSF alone were obtained. The clinical data, the success rate of stem cell collection, hematopoietic reconstitution, and treatment-related adverse reactions between the two groups were evaluated retrospectively. Results: A total of 184 lymphoma patients were included in this analysis, including 115 cases of diffuse large B-cell lymphoma (62.5%) , 16 cases of classical Hodgkin's lymphoma (8.7%) , 11 cases of follicular non-Hodgkin's lymphoma (6.0%) , 10 cases of angioimmunoblastic T-cell lymphoma (5.4%) , 6 cases of mantle cell lymphoma (3.3%) , and 6 cases of anaplastic large cell lymphoma (3.3%) , 6 cases of NK/T-cell lymphoma (3.3%) , 4 cases of Burkitt's lymphoma (2.2%) , 8 cases of other types of B-cell lymphoma (4.3%) , and 2 cases of other types of T-cell lymphoma (1.1%) ; 31 patients had received radiotherapy (16.8%) . The patients in the two groups were recruited with Plerixafor in combination with G-CSF or G-CSF alone. The baseline clinical characteristics of the two groups were basically similar. The patients in the Plerixafor in combination with the G-CSF mobilization group were older, and the number of recurrences and third-line chemotherapy was higher. 100 patients were mobilized with G-CSF alone. The success rate of the collection was 74.0% for one day and 89.0% for two days. 84 patients in the group of Plerixafor combined with G-CSF were recruited successfully with 85.7% for one day and 97.6% for two days. The success rate of mobilization in the group of Plerixafor combined with G-CSF was substantially higher than that in the group of G-CSF alone (P=0.023) . The median number of CD34(+) cells obtained in the mobilization group of Plerixafor combined with G-CSF was 3.9×10(6)/kg. The median number of CD34(+) cells obtained in the G-CSF Mobilization group alone was 3.2×10(6)/kg. The number of CD34(+) cells collected by Plerixafor combined with G-CSF was considerably higher than that in G-CSF alone (P=0.001) . The prevalent adverse reactions in the group of Plerixafor combined with G-CSF were grade 1-2 gastrointestinal reactions (31.2%) and local skin redness (2.4%) . Conclusion: The success rate of autologous hematopoietic stem cell mobilization in lymphoma patients treated with Plerixafor combined with G-CSF is significantly high. The success rate of collection and the absolute count of CD34(+) stem cells were substantially higher than those in the group treated with G-CSF alone. Even in older patients, second-line collection, recurrence, or multiple chemotherapies, the combined mobilization method also has a high success rate of mobilization.

A Single-Center Analysis of the Use of G-CSF Combined with Plerixafor to Mobilize Peripheral Blood Hematopoietic Stem Cell from Healthy Related Donors in Allogeneic Hematopoietic Stem Cell Transplantation / 中国实验血液学杂志

OBJECTIVE@#To study the effect and safety of G-CSF combined with Plerixafor on the mobilization of peripheral blood hematopoietic stem cells from healthy related donors of allogeneic hematopoietic stem cell transplantation (allo-HSCT).@*METHODS@#It was analyzed retrospectively that the data of peripheral blood hematopoietic stem cells from 33 (observation group) related donors mobilized by G-CSF plus Plerixafor in Hebei Yanda Lu Daopei Hospital from April 2019 to April 2021. Bone marrow and peripheral blood hematopoietic stem cells (PBSCs) of these donors were respectively collected on the fourth and fifth day of G-CSF-induced mobilization. Following the administration of Plerixafor on the night of the fifth day, PBSCs were collected on the sixth day once again. 46 donors using "G-CSF only" mobilization method in the same period were randomly selected as the control and respectively analyzed the differences of CD34+ cell counts on the fifth and the sixth day in two groups. And the donors' adverse reaction to Plerixafor in the form of questionnaire was also observed. Then it was compared that the patients who underwent allo-HSCT in "G-CSF+Plerixafor" group and "G-CSF only" group in terms of acute GVHD at grade I-IV or III-IV, CMV reactivation and EBV reactivation.@*RESULTS@#CD34+ cells count (M±Q) among PBSCs collected on the fifth and the sixth day in the observation group were (1.71±1.02)×106/kg and (4.23±2.33)×106/kg, respectively. CD34+ cell counts on the sixth day was significantly higher than that of the fifth day (P<0.001); While the counterparts in the control group were (2.47±1.60)×106/kg and (1.87±1.37)×106/kg, respectively. By statistical analysis, CD34+ cell counts on the sixth day was significantly less than that of the fifth day (P<0.001). The adverse reaction to Plerixafor for the donors in the study were all grade 1 or 2 (mild or moderate) according to CTCAE 5.0 and disappeared in a short time. The patients who underwent allo-HSCT in the "G-CSF+Plerixafor" group and "G-CSF only" group were not statistically significant in terms of acute GVHD at grade I-IV or III-IV, CMV reactivation and EBV reactivation (P>0.1).@*CONCLUSION@#The cell mobilization program of G-CSF combined with Plerixafor is safe and effective for being applied to allo-HSCT. The addition of Plerixafor can significantly increase the number of CD34 postive cells in the PBSC collection. Key words　　; ;

Efficacy and safety of autologous hematopoietic stem cell transplantation in elderly multiple myeloma patients: a single center retrospective study / 中华血液学杂志

Objective: To evaluate the efficacy and safety of autologous hematopoietic stem cell transplantation (auto-HSCT) in elderly patients (≥65 years old) with multiple myeloma (MM) . Methods: From June 1, 2006 to July 31, 2020, 22 MM patients (≥65 years old) who were diagnosed in the First Affiliated Hospital, Sun Yat-sen University and received novel drug induction followed by auto-HSCT were analyzed retrospectively. These patients were evaluated for important organ functions before transplantation, and the International Myeloma Working Group frail score was used in 2016 to screen out transplant-eligible patients. Results: The median (interquartile range, IQR) age at the time of transplantation of the 22 patients was 66.75 (IQR 4.50) years. A total of 20 patients received stem cell mobilization. The median number of mononuclear cells collected was 4.53×10(8)/kg, that of CD34(+) cells was 3.37×10(6)/kg, and the median number of apheresis procedures performed was 2. After stem cell transfusion, the median time of neutrophil implantation was 11 days, that of platelet implantation was 13 days, and the treatment-related mortality was 0 at 100 days after transplantation. The median follow-up was 48.7 months. The median time to progression time was not reached, and the median overall survival time was 111.8 months. Conclusion: Auto-HSCT is a safe and effective treatment for selected elderly patients of 65 years or older with MM.

Analysis of Factors Influencing Autologous Peripheral Blood Stem Cells Mobilization in Patients with Lymphoma and Multiple Myeloma / 中国实验血液学杂志

OBJECTIVE@#To analyze the factors influencing the mobilization of autologous peripheral blood stem cells (auto-PBSCs) in patients with lymphoma and multiple myeloma, and provide reference for optimizing the autologous stem cell mobilization regimen.@*METHODS@#Clinical data of 33 multiple myeloma and lymphoma patients received auto-PBSCs mobilization in our center from January 2015 to December 2018 were collected, the correlation of mobilization failure rate with gender, age, courses of chemotherapy before mobilization, does of recombinant human granulocyte colony stimulating factor (rhG-CSF), type of disease, and chemotherapy regimen were retrospectively analyzed.@*RESULTS@#Type of disease and course of pre-mobilization chemotherapy could affect the mobilization failure rate (P0.05).@*CONCLUSION@#Multi-course chemotherapy before collection and lymphoma patients are poor factors negatively impacting on auto-PBSCs mobilization.

Efficacy and Safety of PEG-rhG-CSF in HSC Mobilization in 71 Normal Healthy Donors for Allogeneic Hematopoietic Stem Cell Transplantation / 中国实验血液学杂志

OBJECTIVE@#To retrospectively analyze the efficacy and safety of pegylated recombinant human granulocyte colony-stimulating factor (PEG-rhG-CSF) in hematopoietic stem cell mobilization in 71 normal healthy donors for allogeneic hematopoietic stem cell transplantation (allo-HSCT).@*METHODS@#From March 2018 to July 2019, 71 patients received allo-HSCT in The General Hospital of Western Theater Command were enrolled in the study, a single dose of PEG-rhG-CSF was injected subcutaneously at 12 mg to all the stem cell donors. After injection for 4 days, CD34@*RESULTS@#Seventy-one healthy stem cell donors included 39 males and 32 females with a median age of 38 (16-58) years old. The median number of CD34@*CONCLUSION@#For allo-HSCT donor mobilization, PEG-rh-G-CSF is effective, safe, and convenient, providing more options for HSC mobilization.

The impact of multiple myeloma induction therapy on hematopoietic stem cell mobilization and collection: 25-year experience

ABSTRACT While first-line induction therapy for patients with multiple myeloma has changed over the years, autologous hematopoietic stem cell transplantation still plays a significant role, improving both depth of response and progression-free survival of myeloma patients. Our 25-year experience in mobilizing hematopoietic stem and progenitor cells for 472 transplant-eligible myeloma patients was retrospectively reviewed. Patients were stratified according to the remission induction therapy received, and the outcomes were compared among the cohorts that received vincristine, adriamycin and dexamethasone (VAD) (n = 232), bortezomib and dexamethasone (BD) (n = 86), cyclophosphamide, bortezomib and dexamethasone (CyBorD) (n = 82) and other regimens (n = 67). Cyclophosphamide plus granulocyte colony-stimulating factor was the predominant mobilization regimen given. A greater number of CD34+ cells (9.9 × 10E6/kg, p = 0.026) was collected with less hospital admissions in BD patients (13%, p = 0.001), when compared to those receiving VAD (7.5 × 10E6/kg, 29%), CyBorD (7.6 × 10E6/kg, 19%), or other regimens (7.9 × 10E6/kg, 36%). Induction therapy did not influence the overall rate of unscheduled visits or the length of hospitalization because of complications following mobilization. The myeloma response was not significantly deepened following the cyclophosphamide administered for mobilization. This analysis demonstrates the importance of monitoring the impact of initial treatment on downstream procedures such as stem cell mobilization and collection.

Biosimilar Filgrastim for Progenitor-Cell Mobilization prior to Autologous Transplantation: Retrospective Analysis of Patients with Multiple Myeloma and Lymphomas / Filgrastim Biossimilar para Mobilização de Células Progenitoras antes do Transplante Autólogo: Análise Retrospectiva de Pacientes com Mieloma Múltiplo e Linfomas / Filgrastim Biosimilar para la Movilización de Células Progenitoras antes del Trasplante Autólogo: Análisis Retrospectivo de Pacientes con Mieloma Múltiple y Linfomas

Introduction: Filgrastim, which plays a key role in peripheral blood progenitor cell (PBPC) harvesting, has been available for nearly 25 years, and several filgrastim biosimilars are available. Objective: We assessed whether a biosimilar filgrastim (Filgrastine®) was associated with effective mobilization in patients undergoing PBPC collection for autologous transplantation. Method: We reviewed the charts of patients with multiple myeloma and lymphomas treated at three institutions in Brazil. The primary outcome (mobilization success rate, MSR) was the proportion of patients in the intention-to-treat (ITT) group in whom at least 2 x 106 CD34+cells/Kg were harvested by leukapheresis on days 5 and/or 6. The per-protocol (PP) group comprised patients who received at least 4 days of Filgrastine and had at least one CD34+ count on days 5 or 6. Results: The daily dose of Filgrastine (on D1, with few changes thereafter) ranged from 8.5 to 28.9 mcg/Kg in the 52 patients in the ITT group, with a median of 13.8 mcg/Kg; 51 patients received at least four doses. A mean of 2.84±1.97 x 106 CD34+cells/Kg were harvested. MSR was 53.9% (95%CI, 39.5%-67.8%) in the ITT group and 62.2% (95%CI, 46.5%-76.2%) in the 45 patients in the PP group. Mobilization was considered effective by investigators in 80.8% of patients in the ITT group and 88.9% of those in the PP group. Conclusion: Despite the study's observational design, the results suggest that Filgrastine® is associated with the expected success rates in PBPC collection for autologous transplantation.

Introdução: O filgrastim, que desempenha um papel fundamental na coleta de células progenitoras de sangue periférico (CPSP), está disponível há quase 25 anos, e existem vários biossimilares de filgrastim sendo comercializados. Objetivo: Avaliar se um filgrastim biossimilar (Filgrastine®) foi associado com mobilização efetiva em pacientes submetidos à coleta de CPSP para transplante autólogo de medula óssea. Método: Foram revisados os prontuários de pacientes com mieloma múltiplo e linfomas tratados em três instituições no Brasil. O desfecho primário (taxa de sucesso de mobilização) foi a proporção de pacientes na população intenção de tratar (ITT), em que pelo menos 2 x 106 células CD34+/kg foram coletadas por leucaférese nos dias 5 e/ou 6. A população per protocolo (PP) foi composta por pacientes que receberam pelo menos quatro dias de Filgrastine e tiveram pelo menos uma contagem de CD34+ nos dias 5 ou 6. Resultados: A dose diária de Filgrastine (no D1, com pequenas alterações subsequentes) variou de 8,5 a 28,9 mcg/Kg nos 52pacientes na população ITT, com uma mediana de 13,8 mcg/Kg; 51 pacientes receberam pelo menos quatro doses. Uma média de 2,84±1,97 x 106 células CD34+/kg foram coletadas. A taxa de sucesso de mobilização foi de 53,9% (IC 95%, 39,5% a 67,8%) na população ITT e 62,2% (IC 95%, 46,5% a 76,2%) nos 45 pacientes da população PP. A mobilização foi considerada efetiva pelos pesquisadores em 80,8% dos pacientes da população ITT e 88,9% daqueles na população PP. Conclusão: Apesar de sua natureza observacional, este estudo sugere que Filgrastine esteja associado com as taxas de sucesso esperadas na coleta de CPSP para transplante autólogo de medula óssea.

Introducción: El filgrastim, que desempeña un papel fundamental en la colecta de células progenitoras de sangre periférica (CPSP), está disponible desde hace casi 25 años y existen varios biosimilares de filgrastim siendo comercializados. Objetivo: Se evaluó si un filgrastim biosimilar (Filgrastine®) se asoció con una movilización efectiva en pacientes sometidos a la colecta de CPSP para el trasplante autólogo de médula ósea. Método: Se revisaron los prontuarios de pacientes con mieloma múltiple y linfomas tratados en tres instituciones en Brasil. El resultado primario (tasa de éxito de movilización) fue la proporción de pacientes en la población intención de tratar (ITT) en que al menos 2 x 106 células CD34+/kg fueron obtenidas por leucoféresis en los días 5 y/o 6. La población por protocolo (PP) fue compuesta por pacientes que recibieron por lo menos 4 días de Filgrastine y tuvieron al menos un recuento de CD34 + en los días 5 o 6. Resultados: La dosis diaria de Filgrastine (en el D1, con pequeños cambios subsiguientes) varió de 8, 5 a 28,9 mcg/Kg en los 52 pacientes en la población ITT, con una mediana de 13,8 mcg / Kg; 51 pacientes recibieron al menos cuatro dosis. Se obtuvo una media de 2,84±1,97 x 106 células CD34+/kg. La tasa de éxito de movilización fue del 53,9% (IC 95%, 39,5% a 67,8%) en la población ITT y el 62,2% (IC 95%, 46,5% a 76,2%), en los 45 pacientes de la población PP. La movilización fue considerada efectiva por los investigadores en el 80,8% de los pacientes de la población ITT y el 88,9% de aquellos en la población PP. Conclusión: A pesar de su naturaleza observacional, este estudio sugiere que Filgrastine está asociado con las tasas de éxito esperadas en la recolección de CPSP para trasplante autólogo de médula ósea.

Bendamustine, etoposide, and dexamethasone to mobilize peripheral blood hematopoietic stem cells for autologous transplantation in non-Hodgkin lymphoma

BACKGROUND: Bendamustine is a chemotherapeutic agent that has shown broad activity in patients with lymphoid malignancies. It contains both alkylating and nucleoside analog moieties, and thus, is not commonly used for stem cell mobilization due to concerns that it may adversely affect stem cell collection. Here we describe the lymphoma subset of a prospective, non-randomized phase II study of bendamustine, etoposide, and dexamethasone (BED) as a mobilization agent for lymphoid malignancies. METHODS: This subset analysis includes diffuse large B-cell lymphoma (N=3), follicular lymphoma (N=1), primary mediastinal B-cell lymphoma (N=1), and NK/T-cell lymphoma (N=1). Patients received bendamustine (120 mg/m² IV d 1, 2), etoposide (200 mg/m² IV d 1–3), and dexamethasone (40 mg PO d 1–4) followed by filgrastim (10 mcg/kg/d sc. through collection). RESULTS: We successfully collected stem cells from all patients, with a median of 7.9×10⁶/kg of body weight (range, 4.4 to 17.3×10⁶/kg) over a median of 1.5 days (range, 1 to 3) of apheresis. All patients who received transplants were engrafted using kinetics that were comparable to those of other mobilization regimens. Three non-hematologic significant adverse events were observed in one patient, and included bacterial sepsis (grade 3), tumor lysis syndrome (grade 3), and disease progression (grade 5). CONCLUSION: For non-Hodgkin lymphoma, mobilization with bendamustine is safe and effective.

The effect of the dexamethasone, cytarabine, and cisplatin (DHAP) regimen on stem cell mobilization and transplant outcomes of patients with non-Hodgkin's lymphoma who are candidates for up-front autologous stem cell transplantation

BACKGROUND/AIMS: Data on dexamethasone, cytarabine, and cisplatin (DHAP) as a mobilization regimen, compared to high-dose cyclophosphamide (HDC), for up-front autologous stem cell transplantation (ASCT) in non-Hodgkin’s lymphoma (NHL) is limited. METHODS: Consecutive patients with aggressive NHL treated with cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP) or rituximab-CHOP who underwent chemomobilization using HDC or DHAP plus granulocyte-colony stimulating factor (G-CSF) for up-front ASCT were enrolled from three institutions between 2004 and 2014. RESULTS: Ninety-six patients (57 men) were included. Sixty-five patients (67.7%) received HDC; and 31 (32.3%), DHAP. The total CD34+ cells mobilized were significantly higher in patients receiving DHAP (16.1 vs. 6.1 × 106/kg, p = 0.001). More patients achieved successful mobilization with DHAP (CD34+ cells ≥ 5.0 × 106/kg) compared to HDC (87.1% vs. 61.5%, respectively; p = 0.011), particularly within the first two sessions of apheresis (64.5% vs. 32.3%, respectively; p = 0.003). Mobilization failure rate (CD34+ cells < 2.0 × 106/kg) was significantly higher in patients receiving HDC (20.0% vs. 3.2%, p = 0.032). On multivariate analysis, the DHAP regimen (odds ratio, 4.12; 95% confidence interval, 1.12 to 15.17) was an independent predictor of successful mobilization. During chemomobilization, patients receiving HDC experienced more episodes of febrile neutropenia compared to patients receiving DHAP (32.3% vs. 12.9%, p = 0.043). CONCLUSIONS: The DHAP regimen was associated with a significantly higher efficacy for stem cell mobilization and lower frequency of febrile neutropenia. Therefore, DHAP plus G-CSF is an effective for mobilization in patients with aggressive NHL who were candidates for up-front ASCT.

Analysis of Success Rate and Influencing Factors for Collecting Peripheral Blood Hematopoietic Stem Cells by Combination of CTX or E-CHOP Chemotherapy with Mobilization of G-CSF in Patients with Multiple Myeloma / 中国实验血液学杂志

<p><b>OBJECTIVE</b>To analyze the success rate and influencing factors for collecting peripheral blood hematopoietic stem cells (HSC) by combination of cyclophosphamide (CTX) or E-CHOP chemotherapy combined with granulocyte colony stimulating factor (G-CSF) in patients with multiple myeloma.</p><p><b>METHODS</b>The clinical data of 75 patients with multiple myeloma in our hospital were retrospectively analyzed. All patients received CTX or E-CHOP chemotherapy combined with G-CSF mobilization to collect HSC, and the success rate (CD34 cell numbers was at least 2×10/kg) and its influencing factors were statistically analyzed.</p><p><b>RESULTS</b>A total of 86 collections by mobilization were performed in 75 patients, with the average 3.22 (0.12-22.28)×10/kg of CD34 cells, and the success rate of 74.42%. Single factor analysis revealed that the course number of chemotherapy and disease status before the collection significantly correlated with the success rate of HSC collection (P<0.05), and sex, age, disease type, ISS stage and mobilization method showed no significant correlation with the collection success rate (P>0.05). Multivariate Logistic regression analysis showed that the course number of chemotherapy positively related with the success rate of HSC collection (OR=2.95, 95% CI: 1.60-5.41, P<0.01), and there was no significant correlation with the disease status before collection (OR=1.01, 95% CI: 0.88-1.16, P=0.89).</p><p><b>CONCLUSION</b>There are no significant effects of sex, disease type, ISS staging and mobilization methods on the success rate of HSC collection in patients with multiple myeloma, and the less course number of chemotherapy (<5) before collection show a higher success rate of HSC collection.</p>

Differences in Mobilization Efficiency between Small Children and Adults with Healthy Marrows / 임상소아혈액종양

BACKGROUND: We compared the yields of mobilized PBSCs from single day of normal volume leukapheresis (NVL) in children and adults, and factors affecting the yields, to understand differences in mobilization efficiency between adults and small children with healthy marrows.METHODS: This study involved 18 adult volunteer donors and 47 small children weighing less than 20 kg who participated in a clinical trial of cell therapy in children with cerebral palsy. Donor factors analyzed to identify predictors of the yield of apheresis included age, gender, weight and complete blood cell count (CBC) with differential counts as well as equipment parameters.RESULTS: The yields of total nucleated cells (TNCs) and CD34⁺cells in the apheresis products of the children were significantly lower than in those from healthy adults. However, the efficiency of recovery of PBSCs (total CD34⁺ cell counts/TNCs) was significantly higher in small children (0.48±0.30%) than in adults (0.10±0.05%) (P < 0.05). Multivariable analysis of adult donor factors showed that the processed volume and flow rate of apheresis were significantly associated with the yield of TNCs (P < 0.05, for both), but not of CD34⁺cells. However, in multivariable analysis of child donor factors, body weight and circulating WBC count on the day of apheresis were significantly associated with the yield of TNCs (P < 0.05, for both) and of CD34⁺cells (P < 0.05, for both).CONCLUSION: The predictors of PBSC yields from a single day of NVL in adults and small children are different. Also mobilization is more effective in small children than in adults.

Differences in Mobilization Efficiency between Small Children and Adults with Healthy Marrows / 임상소아혈액종양

BACKGROUND: We compared the yields of mobilized PBSCs from single day of normal volume leukapheresis (NVL) in children and adults, and factors affecting the yields, to understand differences in mobilization efficiency between adults and small children with healthy marrows. METHODS: This study involved 18 adult volunteer donors and 47 small children weighing less than 20 kg who participated in a clinical trial of cell therapy in children with cerebral palsy. Donor factors analyzed to identify predictors of the yield of apheresis included age, gender, weight and complete blood cell count (CBC) with differential counts as well as equipment parameters. RESULTS: The yields of total nucleated cells (TNCs) and CD34⁺cells in the apheresis products of the children were significantly lower than in those from healthy adults. However, the efficiency of recovery of PBSCs (total CD34⁺ cell counts/TNCs) was significantly higher in small children (0.48±0.30%) than in adults (0.10±0.05%) (P < 0.05). Multivariable analysis of adult donor factors showed that the processed volume and flow rate of apheresis were significantly associated with the yield of TNCs (P < 0.05, for both), but not of CD34⁺cells. However, in multivariable analysis of child donor factors, body weight and circulating WBC count on the day of apheresis were significantly associated with the yield of TNCs (P < 0.05, for both) and of CD34⁺cells (P < 0.05, for both). CONCLUSION: The predictors of PBSC yields from a single day of NVL in adults and small children are different. Also mobilization is more effective in small children than in adults.

Hematopoietic stem cell mobilization: current status and future perspective

No abstract available.

Mobilization of hematopoietic progenitor cells for autologous transportation: consensus recommendations / Mobilização de células progenitoras hematopoéticas para transplante autólogo: recomendações de consenso

SUMMARY Selected patients with certain hematological malignancies and solid tumors have the potential to achieve long-term survival with autologous hematopoietic progenitor cell transplant. The collection of these cells in peripheral blood avoids multiple bone marrow aspirations, results in faster engraftment and allows treatment of patients with infection, fibrosis, or bone marrow hypocellularity. However, for the procedure to be successful, it is essential to mobilize a sufficient number of progenitor cells from the bone marrow into the blood circulation. Therefore, a group of Brazilian experts met in order to develop recommendations for mobilization strategies adapted to the reality of the Brazilian national health system, which could help minimize the risk of failure, reduce toxicity and improve the allocation of financial resources.

RESUMO Pacientes selecionados com certas neoplasias hematológicas e tumores sólidos têm o potencial de alcançar sobrevida de longo prazo com o transplante autólogo de células progenitoras hematopoéticas. A coleta dessas células no sangue periférico evita múltiplas aspirações de medula óssea, resulta em enxertia mais rápida, e permite o tratamento de pacientes com infiltração, fibrose ou hipocelularidade medular. Contudo, para o sucesso desse procedimento, é essencial mobilizar um número suficiente de células progenitoras da medula óssea para a circulação sanguínea. Por isso, um painel de especialistas brasileiros se reuniu com o objetivo de desenvolver recomendações para estratégias de mobilização adaptadas à realidade do sistema de saúde nacional, que pudessem contribuir para minimizar os riscos de falha, reduzir a toxicidade e melhorar a alocação de recursos financeiros.

Analysis of Factors Influencing Peripheral Blood Stem Cell Collection of 151 Lymphoma Cases / 中国实验血液学杂志

<p><b>OBJECTIVE</b>To analyze the influential factors related to mobilization and collection of stem cells so as to improve the collection efficiency of autologous peripheral stem cell transplantation in lymphoma patients.</p><p><b>METHODS</b>The peripheral blood stem cell collection data of 151 cases of lymphoma in our hospital was analyzed retrospectively. The relationship between the harvested CD34(+) stem cells and some factors, such as age, sex, height, weight, histological type, staging, mobilization programs, collecting days, blood transfusion, time and duration of chemotherapy, was analyzed.</p><p><b>RESULTS</b>The single factor analysis showed that sex, height, weight, histological type, staging, mobilization program, collecting days, blood transfusion were not significantly associated with CD34(+) stem cells collection, respectively. Age (r = -0.248, P = 0.002), duration of sick and cycles of chemotherapy were significantly associated with CD34(+) cell collection. At the age older than 50 years, the collected CD34(+) cell number decreased significantly; and at the age older than 60 years, the CD34(+) cell number was greatly reduced; CD34(+) cells non-significantly correlated with peripheral blood WBC (r = 0.053, P = 0.527), but significantly with the percentage of mononuclear cells (r = 0.260, P = 0.002) and the absolute value of mononuclear cells (r = 0.338, P = 0.00003) .</p><p><b>CONCLUSION</b>The patients less than 60 years old, fewer chemotherapy cycles, shorter duration time or PB mononuclear cells between (2-6) × 10(9)/L may contribute to the better mobilization and collection of peripheral blood stem cells.</p>

Comparison of CCR5 Expression on T Lymphocytes between the Bone Marrow and Peripheral Blood Grafts after Mobilization / 中国实验血液学杂志

<p><b>OBJECTIVE</b>To compare the expression of C-C chemokine receptor type 5 (CCR5) on T cells between bone marrow grafts (G-BM) and peripheral blood grafts (G-PB) nobilized by recombinant human granulocyte colony-stimulating factor (rhG-CSF), and to analyze the correlation of CCR5+ T lymphocyte expression in the grafts with the occurrence of acute GVHD.</p><p><b>METHODS</b>Forty-six healthy donor and their recipient pairs of related allogeneic hematopoietic stem cell transplantation (allo-HSCT) were enrolled in this study. All the recipients were received the infusion of G-BM and G-PB. The relative proportion and quantity of CCR5+ T cell subset in G-BM and G-PB were detected and compared. Then the correlation of the quantity of infused CCR5+ T cells with the occurrence of acute GVHD was analyzed.</p><p><b>RESULTS</b>After mobilization, the proportions of CD4+ CCR5+ and CD8+ CCR5+ T cells occupying T cells in G-PB were both lower than those in G-BM. However, the absolute counts in G-PB were 15-25 times more than those in the bone marrow. And the absolute counts could not predict the occurrence of acute GVHD after transplantation (P>0.05).</p><p><b>CONCLUSION</b>The difference of CCR5+ subsets between G-PB and G-BM may partially explain that grafts from different sources have different immunologic characteristics. Besides, the quantity of CCR5+ T cells in the grafts are not related with the occurrence of acute GVHD. However, the relative proportion of CCR5+ T cell subset in the grafts may be predictive of acute GVHD.</p>

Stem Cells and Lung Regeneration

Tissues such as the lung, liver, and pancreas that have a low steady-state cell turnover yet can respond robustly after injury to replace damaged cells. The airway epithelium is exposed to inhaled particles and pathogens that may lead to the development of a many infectious and inflammatory respiratory diseases. Lung transplantation is an accepted modality of treatment for end-stage lung diseases. Since the early 1990 s, more than 26,000 lung transplants have been performed at centers worldwide. However, the availability of donor tissues and organs is limited, which presents a serious limitation for widespread transplantation surgery. The appearance of bioengineered lung and tracheal tissue transplants is considered a promising alternative to the classical transplantation of donor organ/tissue. Stem cells therapy arises as a new therapeutic approach, with a wide application potential.