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.
Humans ; Granulocyte Colony-Stimulating Factor/therapeutic use* ; Hematopoietic Stem Cell Mobilization/methods* ; Hematopoietic Stem Cell Transplantation ; Heterocyclic Compounds/adverse effects* ; Lymphoma/drug therapy* ; Lymphoma, T-Cell/therapy* ; Multiple Myeloma/drug therapy* ; Retrospective Studies ; Transplantation, Autologous

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.
Male ; Humans ; Female ; Multiple Myeloma/diagnosis* ; Hematopoietic Stem Cell Transplantation/adverse effects* ; Retrospective Studies ; Creatinine ; Hematopoietic Stem Cell Mobilization ; Transplantation, Autologous ; Dexamethasone/therapeutic use* ; Antineoplastic Combined Chemotherapy Protocols/therapeutic use* ; Heterocyclic Compounds/therapeutic use* ; Bortezomib/therapeutic use* ; Cyclophosphamide/therapeutic use* ; Stomatitis/etiology*

OBJECTIVE: To evaluate the efficacy and safety of etoposide combined with cyclophosphamide (EC) regimen for mobilization of autologous peripheral blood stem cells (APBSCs) in patients with multiple myeloma (MM). METHODS: The clinical data of 48 MM patients who received APBSC transplantation (APBSCT) in Department of Hematology of the First Affiliated Hospital of Nanchang University from January 2015 to October 2021 were retrospectively analyzed. The mobilization success rate and mobilization optimal rate of EC regimen were counted, and its effect on transplant efficacy, adverse reactions, hematopoietic reconstitution after transplantation, and survival time of MM patients were analyzed. RESULTS: APBSCs were collected on day 14 (10-19) after EC administration. The median of collected CD34⁺ cells was 6.82 (1.27-22.57)×10⁶/kg, and the median number of apheresis session was 2 (1-4). The mobilization success rate (collecting CD34⁺ cells≥2×10⁶ cells/kg after completion of apheresis) was 98% (47/48), and mobilization optimal rate (collecting CD34⁺ cells≥5×10⁶ cells/kg after completion of apheresis) was 71% (34/48). The depth of remission were improved after APBSCT, and the complete remission (CR) rate increased from 45.8% before transplantation to 87.5% after transplantation (P <0.01). There was no transplant-related death, no blood transfusion during mobilization, and no mucositis occurred in the patients. The most common complication was neutropenia, with an incidence of 75.0% (36/48). After transplantation, all the patients successfully achieved hematopoietic reconstitution. The median time to neutrophil engraftment was 10 (9-26) days, and median time to platelet engraftment was 10 (8-33) days. By the end of follow-up, both the median progression-free survival (PFS) and overall survival (OS) time were not reached. The 5-year estimated PFS rate and OS rate was 53.8% and 82.4%, respectively. CONCLUSION The EC regimen for mobilization of APBSC has a high acquisition success rate and controllable adverse reactions, which can be an effective and safe mobilization regimen in MM patients.
Humans ; Multiple Myeloma/therapy* ; Etoposide/therapeutic use* ; Peripheral Blood Stem Cells ; Hematopoietic Stem Cell Mobilization/adverse effects* ; Retrospective Studies ; Granulocyte Colony-Stimulating Factor ; Cyclophosphamide/therapeutic use* ; Hematopoietic Stem Cell Transplantation/adverse effects* ; Transplantation, Autologous/adverse effects*

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.
Aged ; Hematopoietic Stem Cell Mobilization/methods* ; Hematopoietic Stem Cell Transplantation/adverse effects* ; Humans ; Multiple Myeloma/drug therapy* ; Retrospective Studies ; Transplantation, Autologous/methods* ; Treatment Outcome

BACKGROUNDThe effects of donor characteristics on CD34(+) cell dose remain controversial. Recently, we developed a novel haploidentical transplant protocol, in which mixture allografts of granulocyte colony-stimulating factor (G-CSF)-primed bone marrow (G-BM) and G-CSF-mobilized peripheral blood (G-PB) were used. The aim of this study was to investigate the effects of donor characteristics on CD34(+) cell dose in mixture allografts of G-BM and G-PB.

METHODSA total of 162 healthy adult donors, who underwent bone marrow harvest and peripheral blood collection between January 2009 and November 2010 in Peking University People's Hospital, were prospectively investigated. G-CSF was administered subcutaneously at a dose of 5 µg/kg once a day for 5-6 consecutive days. Bone marrow and peripheral blood stem cells were harvested on the fourth day and fifth day, respectively. A final total CD34(+) cell dose less than 2×10(6) cells/kg recipient body weight was considered a poor mobilization.

RESULTSOf the 162 donors, 31 (19.1%) did not attain this threshold. The obtained median CD34(+) cell doses in bone marrow, peripheral blood, and mixture allografts were 0.83×10(6)/kg, 2.40×10(6)/kg, and 3.47×10(6)/kg, respectively. Multiple regression analysis showed that donor age had a significant negative effect on CD34(+) cell dose in either G-BM, or G-PB, or mixture allografts of G-BM and G-PB. And a 1-year increase in age was associated with a 5.6% decrease in the odds of achieving mobilization cutoff. No significant correlation was found for donor gender, body mass index (BMI), and weight.

CONCLUSIONDonor age is the only factor among the four parameters, including age, gender, weight, and BMI, that influence CD34(+) cell dose in mixture allografts of G-BM and G-PB, and younger donors should be chosen to obtain sufficient CD34(+) cells for transplantation.

Adolescent ; Adult ; Aged ; Allografts ; Antigens, CD34 ; metabolism ; Bone Marrow ; Bone Marrow Transplantation ; adverse effects ; Female ; Granulocyte Colony-Stimulating Factor ; metabolism ; Hematopoietic Stem Cell Mobilization ; adverse effects ; Humans ; Male ; Middle Aged ; Prospective Studies ; Tissue Donors ; Young Adult

This study was to investigate the differential regulation of CCR5 expression on T cells in healthy donors after mobilization with recombinant human granulocyte colony-stimulating factor (rhG-CSF) and analyze its correlation with acute graft-versus-host disease (aGVHD) so as to understand the possible mechanisms underlying rhG-CSF-induced immune tolerance. Sixty-eight related healthy donor and their corresponding recipient for allogeneic hematopoietic stem cell transplantation (allo-HSCT) were enrolled in this study. The expression of CCR5 on CD4(+) and CD8(+) T cells in the peripheral blood (PB) before and after mobilization were detected by using flow cytometry (FCM) respectively. According to the changes of CCR5 expression on CD4(+) and CD8(+) T cells, the Sixty-two evaluable donors were divided into the downregulated and unchanged/upregulated (non-downregulated) groups, and the incidence of grades II to IV aGVHD in two groups were compared. The results showed that the mean value of CCR5 expression on CD4(+) and CD8(+) T cells in PB was not different significantly after mobilization (P > 0.05). Apparent inconsistency was showed among different individuals. Thirty-four (50%) donors displayed downregulation of CCR5 expression, while 34 (50%) donors manifested unchanged or upregulated CCR5 expression on CD4(+) T cells. CCR5 expression on CD8(+) T cells was downregulated in 42 (61.8%), unchanged or upregulated in 26 (38.3%) donors. The cumulative incidence of grades II to IV aGVHD in the downregulated and non-downregulated groups for CD4(+) T cells were 16.1% and 41.9% (P = 0.032), and recipients with CCR5 downregulation on CD8(+) T cells showed an increased tendency of developing aGVHD (37.8% vs 16.0%, P = 0.065). In conclusion, rhG-CSF mobilization could lead to differential regulation of CCR5 expression on T cells, which might influence the migration of T cells in vivo, decrease T cell trafficking towards GVHD target organs, and thus reduce the incidence of aGVHD after transplantation.
Adolescent ; Adult ; Blood Donors ; Child ; Child, Preschool ; Female ; Gene Expression Regulation ; Graft vs Host Disease ; pathology ; Granulocyte Colony-Stimulating Factor ; pharmacology ; Hematopoietic Stem Cell Mobilization ; Hematopoietic Stem Cell Transplantation ; adverse effects ; Humans ; Male ; Middle Aged ; Receptors, CCR5 ; metabolism ; T-Lymphocytes ; drug effects ; metabolism ; Young Adult

OBJECTIVETo investigate the impact of the mobilization with the antagonist of the stromal cell-derived factor receptor CXCR4 (AMD3100) (plerixafor), granulocyte-colony-stimulating factor (G-CSF) alone and in combination on the proliferation and cytotoxic functions of the murine splenic lymphocytes.

METHODSC57BL/6(H-2(b)) mice, as donors, were mobilized by, AMD3100, G-CSF alone or in combination (n = 10 mice in each group), and phosphate buffered saline (PBS). Then, the proliferation capacity of murine lymphocytes either in response to the phytohemagglutinin (PHA) stimulation or the mixed lymphocytes reaction (MLR) with allo-lymphocytes from the BALB/C(H-2(d)) mice were detected by CCK-8 method. The cytotoxic capacity of murine lymphocytes on Yac-1 tumor cells was examined by LDH assay.

RESULTSThe proliferation capacity and the responsiveness to alloantigen of the lymphocytes derived from the mice spleen mobilized by AMD3100, G-CSF alone or in combination were significantly lower than those by PBS control (P < 0.05), and those combination of AMD 3100 and G-CSF group were significantly lower than in other groups(P < 0.05). At the effector-target ration of 40:1, the cytotoxic capacity of murine lymphocytes in above mobilization groups was lower than in control group, but no statistically significant difference (P > 0.05).

CONCLUSIONBoth the proliferation capacity and the responsiveness to alloantigen of the murine lymphocytes decreases significantly after the mobilization with AMD3100, G-CSF alone or in combination, whereas no significant alternations are demonstrated on the cytotoxic capacity of murine lymphocytes. Further studies are needed to clarify the underlying mechanisms.

Animals ; Cell Proliferation ; Granulocyte Colony-Stimulating Factor ; adverse effects ; pharmacology ; Hematopoietic Stem Cell Mobilization ; methods ; Hematopoietic Stem Cell Transplantation ; methods ; Heterocyclic Compounds ; administration & dosage ; pharmacology ; Lymphocytes ; drug effects ; immunology ; Mice ; Mice, Inbred BALB C ; Mice, Inbred C57BL ; Receptors, CXCR4 ; drug effects ; Sincalide

OBJECTIVEAutologous peripheral blood stem cell transplantation (APBSCT) is an important method for treatment of malignant solid tumors in children. The mobilization and collection of blood stem cells is crucial for APBSCT. This study aimed to evaluate the clinical efficacy of mobilization and collection of blood stem cells by CIE or IEV chemotherapy protocol in APBSCT in children with neuroblastoma (NB) or rhabdomyosarcoma.

METHODSThe protocols of CIE (cisplatin, etoposide) and IEV (vincristine, dosfamide, etoposide) were used as mobilization chemotherapy in 8 cases of NB with stage IV and 3 cases of rhabdomysacoma with stage III, respectively. The results of the mobilization of blood stem cells were observed.

RESULTSOf the 11 cases, mononuclear cells (MNC) and CD34+ cells were successfully collected and the volume of MNC and CD34 averaged (5.55 ± 1.43)× 10(8)/kg and (4.88 ± 2.48) × 10(6)/kg, respectively. No severe complications were observed during the mobilization and collection. A rapid hemopoietic reconstitution was observed in 10 children after APBSCT. One with NB out of the 10 children died of left heart failure 32 days after APBSCT. Others (9 cases) showed a nearly normal result of routine peripheral blood test 60 days after APBSCT.

CONCLUSIONSCIE or IEV protocol is effective and safe for the mobilization and collection of peripheral blood stem cells in children with NB or rhabdomysacoma.

Antineoplastic Combined Chemotherapy Protocols ; administration & dosage ; pharmacology ; Child ; Child, Preschool ; Epirubicin ; administration & dosage ; Etoposide ; administration & dosage ; Female ; Granulocyte Colony-Stimulating Factor ; pharmacology ; Hematopoietic Stem Cell Mobilization ; adverse effects ; methods ; Humans ; Ifosfamide ; administration & dosage ; Male ; Neuroblastoma ; therapy ; Peripheral Blood Stem Cell Transplantation ; Recombinant Proteins ; Rhabdomyosarcoma ; therapy ; Transplantation, Autologous

The study was aimed to compare the safety of hematopoietic stem cell mobilization and collection in related donors providing bone marrow and peripheral blood stem cells and in unrelated donors providing peripheral blood stem cells only. 100 related donors from September 2005 to August 2006 at Institute of Hematology & People Hospital, Peking University, and 71 unrelated donors from November 2003 to December 2007 in Data Bank of Chinese Hematopoietic Stem Cell Donor Beijing Management Center, were observed in process of bone marrow and peripheral blood stem cell mobilization, collection, and follow-up. The change of hematologic parameters (white blood cell count, platelet count and hemoglobin level) and the side effects were recorded and evaluated on months 1, 3 and 6 as well as annually after PBSC donation. During follow-up, long-term side effects and life quality were investigated by questionnaires. The results showed that the total MNC count of bone marrow and PBSC from related donors was 6.70 (4.11 - 12.23) x 10⁸/kg, and the total CD34(+) cell count was 3.40 (1.61 - 13.57) x 10⁶/kg; the total MNC count of PBSC from unrelated donors was 6.69 (3.35 - 11.48) x 10⁸/kg, and the total CD34(+) cell count was 3.50 (1.15 - 11.60) x 10⁶/kg. The main side effect of mobilization was bone pain, reported in 47.0% of the related donors and in 43.7% of unrelated ones, the main side effect of collection was paresthesia, reported in 25.0% of the related donors and in 29.6% of unrelated ones, there was no significant difference on side effects between related and unrelated donors during mobilization and collection of hematopoietic stem cells, all donors could endure these side effects, and no donor discontinued G-CSF administration because of side effects. After collection, the hemoglobin level of related donors was lower than that of unrelated donors [(125.8 ± 20.2) g/L vs (143.2 ± 20.1) g/L] (p < 0.05) because of bone marrow and peripheral blood collection, and the platelet count of unrelated donors were lower than that of related donors [(126.2 ± 57.2) x 10⁹/L vs (162.4 ± 72.9) x 10⁹/L] (p < 0.05) because of more than two times of collection. There was no significant difference on hematologic parameters between two groups during long-term follow-up, and the majority of the donors reported were in good or very good health. It is concluded that the donation proved from related and unrelated donors is safe to mobilize hematopoietic stem cells for allogeneic transplantation. Long-term monitoring of healthy PBSC donors remains important to guarantee the safety standards of bone marrow and peripheral blood stem cell mobilization and collection, including comprehensive medical examination before mobilization and collection, careful manipulation during collection, long term follow up after collection and so on.
Adolescent ; Adult ; Blood Donors ; Blood Specimen Collection ; adverse effects ; methods ; Female ; Hematopoietic Stem Cell Mobilization ; methods ; Hematopoietic Stem Cell Transplantation ; adverse effects ; methods ; Humans ; Male ; Middle Aged ; Transplantation, Homologous ; Young Adult

This study was aimed to evaluate the effects of recombinant human interleukin 11 (rhIL-11) and recombinant human granulocyte colony stimulating factor (rhG-CSF) in mobilization for autologous peripheral blood stem cell transplantation (APBSCT). 16 patients with non-Hodgkin's lymphoma or acute myeloblastic leukemia were given myelosuppressive chemotherapy, then were mobilized by using rhG-CSF 5 microg/(kg.d) for median 5.5 days and rhIL-11 50 microg/(kg.d) for median 4 days (experimental group) or rhG-CSF 5 microg/(kg.d) alone for median 5.5 days (control group). After mobilizing, the peripheral blood leucocyte and platelet counts, total mononuclear cells, CD34+ cells and CFU-GM counts in PBSC collection, and amount of apheresed platelet transfusion were assayed. The results showed that the peripheral blood leucocyte and platelet counts, total mononuclear cell, CD34+ cell and CFU-GM counts in PBSC collection were no significant difference between two groups (p>0.05). After APBSCT, the median time for neutrophil count>or=0.5x10(9)/L and the median time for platelet count>or=20x10(9)/L were 10.5 and 11.5 days in experimental group, while were 13 and 13 days in control group, respectively. The median amount of apheresed platelet transfusion was 3.5 unit in experimental group and 5 unit in control group. Data were significantly different between two groups (p<0.05). The adverse reactions of mobilization were mild fever, fatigue, symptoms like as common cold, poor appetite, dizziness, muscular soreness in experimental group, but only mild fever in control. These symptoms were well tolerated and overcome with drug withdrawal. It is concluded that the regimen of rhIL-11 in combination with rhG-CSF after myelosuppressive chemotherapy to mobilize PBSC is efficient and safe with rapid hematologic reconstitution and less platelet transfusions after APBSCT were used.
Adolescent ; Adult ; Female ; Granulocyte Colony-Stimulating Factor ; administration & dosage ; Hematopoietic Stem Cell Mobilization ; adverse effects ; methods ; Humans ; Interleukin-11 ; administration & dosage ; Leukemia, Myeloid, Acute ; therapy ; Lymphoma, Non-Hodgkin ; therapy ; Male ; Middle Aged ; Peripheral Blood Stem Cell Transplantation ; methods ; Recombinant Proteins ; Transplantation, Autologous ; Young Adult