El trasplante de progenitores hematopoyéticos y la terapia celular: el valor agregado en el tratamiento del paciente hemato-oncológico / Hematopoietic stems cell transplantation and cell therapy: added value in the treatment of hematopoietic patients

El trasplante de progenitores hematopoyéticos se ha convertido en una opción curativa y de sobrevida libre de enfermedad que las alcanzadas con otras modalidades terapéuticas en ciertas patologías congénitas o tumorales. A inicios del año 2006 se diseñó el proyecto para la creación de la Unidad de Trasplante de progenitores hematopoyéticos del Hospital de SOLCA ­Guayaquil. En Junio de 2006, la Unidad de Trasplante de Médula Ósea (UTMO) inicia los primeros trasplantes, uno autólogo y otro alogénico, y a partir de entonces se han realizado 375 trasplantes de progenitores hematopoyéticos, de los cuales 166 han sido de tipo alogénicos, 147 con progenitores hematopoyéticos obtenidos desde la sangre periférica o médula ósea propiamente dicha y 19 con células obtenidas desde la sangre de cordón umbilical, así como 209 trasplantes de tipo autólogo. Actualmentese ha diseñado un proyecto de ampliación que contempla una infraestructura con 20 habitaciones para hospitalización y un área para manipulación celular más amplia con equipamiento complementario, lo cual permitirá incrementar la cartera de servicios, a saber: la opción del trasplante alogénico de tipo haploidéntico y ciertos procedimientos de inmunoterapia adoptiva con células T

Hematopoietic stem cell transplantation has become a curative and disease-free survival option than those achieved with other therapeutic modalities in specific congenital or tumor pathologies. At the beginning of 2006, the project for the creation of the Hematopoietic Stem Cell Transplant Unit of the Hospital de SOLCA ­ Guayaquil was designed. In June 2006, the Bone Marrow Transplant Unit (UTMO) began the first transplants, one autologous and the other allogeneic. Since then, 375 hematopoietic progenitor transplants have been performed, of which 166 have been allogeneic, 147 with hematopoietic progenitors obtained from peripheral blood or bone marrow itself, and 19 with cells obtained from umbilical cord blood, as well as 209 autologous transplants. An expansion project has been designed that includes an infrastructure with 20 rooms for hospitalization and a larger area for cell manipulation with complementary equipment, which will make it possible to increase the portfolio of services, namely: the option of haploidentical allogeneic transplantation and specific adoptive T-cell immunotherapy procedures.

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　　; ;

Dose-enhanced immunochemotherapy followed by first-line autologous peripheral blood stem cell transplantation for young patients with high-risk aggressive B-cell lymphoma: an efficacy and prognostic factor analysis / 中华血液学杂志

Objective: This study aimed to determine the efficacy of dose-enhanced immunochemotherapy followed by autologous peripheral blood stem cell transplantation (ASCT) in young patients with newly diagnosed high-risk aggressive B-cell lymphoma. Methods: A retrospective study was conducted to examine the clinical and survival data of young patients with high-risk aggressive B-cell lymphoma who received dose-enhanced immunochemotherapy and ASCT as first-line treatment between January 2011 and December 2018 in Blood Diseases Hospital. Results: A total of 63 patients were included in the study. The median age range was 40 (14-63) years old. In terms of the induction therapy regimen, 52 cases received R-DA-EP (D) OCH, and the remaining 11 received R-HyperCVAD/R-MA. Sixteen (25.4% ) patients achieved partial response in the mid-term efficacy assessment, and ten of them were evaluated as complete response after transplantation. The median follow-up was 50 (8-112) months, and the 3-year progression-free survival (PFS) rate and overall survival (OS) rate were (83.9±4.7) % and (90.4±3.7) % , respectively. Univariate analysis demonstrated that age-adjusted international prognostic index ≥2 scores was a negative prognostic factor for OS (P=0.039) , and bone marrow involvement (BMI) was an adverse prognostic factor for OS (P<0.001) and PFS (P=0.001) . However, multivariate analysis confirmed that BMI was the only independent negative predictor of OS (P=0.016) and PFS (P=0.001) . Conclusions: The use of dose-enhanced immunochemotherapy in combination with ASCT as first-line therapy in the treatment of young, high-risk aggressive B-cell lymphoma results in good long-term outcomes, and BMI remains an adverse prognostic factor.

Efficacy and Relapse Prediction Model of Allogeneic Peripheral Blood Stem Cell Transplantation in Adult Acute Leukemia / 中国实验血液学杂志

OBJECTIVE@#To observe the clinical efficacy of allogeneic peripheral blood stem cell transplantation（allo-HSCT） on the treatment of adult acute leukemia patients, moreover, to establish and evaluate a Logistic model to predict the risk of relapse in adult acute leukemia patients after allo-HSCT.@*METHODS@#The clinical data of 145 adult acute leukemia patients treated by peripheral blood stem cell transplantation in the First Affiliated Hospital of Xi'an Jiaotong University from January 2010 to December 2019 was enrolled and analyzed retrospectively. Complications and survival of patients were observed. The relationship between patients' age, diagnosis, leukocyte count at onset, risk stratification, time of diagnosis to transplantation, HCT-CI, minimal residual disease pre-transplantation, donor-recipient sex relationship, HLA match degree, prophylaxis of graft versus host disease(GVHD), donor age, number of transfused mononuclear cells, CD34 positive cells, engraftment time, acute and chronic GVHD, CMV, EBV infection, and hemorrhagic cystitis and recurrence after transplantation were analyzed by logistic regression. Relapse prediction model was established and evaluated according to the results.@*RESULTS@#Among 145 acute leukemia patients, 81 with acute myeloid leukemia, 64 with acute lymphocytic leukemia, 18 with EBV infection, 2 with post-transplant lymphoproliferative disorder(PTLD), 85 with CMV, 26 with hemorrhagic cystitis, 65 patients developed acute GVHD, 51 patients developed chronic GVHD and 45 patients relapsed. The overall survival （OS） rates in one and three years were 86.4% and 61.8%, and the progress-free survival （PFS） rates in one and three years were 67.5% and 62.4%, respectively. There were significant differences in OS and PFS between relapsed and non-relapsed patients, as well as AML and ALL patients. Univariate analysis revealed that patient's age, risk stratification, time to transplantation, HCT-CI index, ATG based GVHD prophylaxis, minimal residual disease pre-transplantation, GVHD prophylaxis, and acute and chronic GVHD were associated with the relapse of disease, multivariate logistic regression analysis showed that pre-transplantation minimal residual disease showed positively correlation with relapse of the disease, while chronic GVHD showed negatively correlation.@*CONCLUSION@#The relapse rate of adult acute leukemia patients treated with allo-HSCT in our hospital is 31.0%, and OS of AML patients is better than ALL patients'. OS of relapsed patients is significantly lower than non-relapsed patients'. Pre-transplantation minimal residual disease is a risk factor of relapse. The risk of relapse is reduced in patients with chronic GVHD.

Fludarabine and intravenous busulfan conditioning with post-transplantation cyclophosphamide for allogeneic peripheral stem cell transplantation for adult patients with lymphoid malignancies: a prospective single-arm phase II study / 医学前沿

Post-transplantation cyclophosphamide (PT-Cy) alone or in combination with other immunosuppressive drugs has emerged as a promising strategy in the setting of allogeneic hematopoietic stem cell transplantation. Improved survival rate was reported in lymphoid malignancies following PT-Cy strategy compared with myeloid disease in non-myeloablative bone marrow transplant setting. Thus, we aimed to evaluate the safety and efficacy of PT-Cy combined with cyclosporine as graft-versus-host disease (GVHD) prophylaxis after myeloablative conditioning and T cell-replete peripheral stem cell transplantation in lymphoid malignancies. This single-arm phase II clinical trial (NCT01435447) involving 31 adult patients was conducted from January 2013 to June 2018. The donor-type neutrophil engraftment rate was 100%, and the overall incidence of grade II to IV and grade III to IV acute GVHD was 39% and 24%, respectively. The cumulative incidence rates of chronic GVHD (35%), including moderate to severe forms (10%), were reduced compared with those of the historical group (P = 0.03 and P = 0.04, respectively). With a median follow-up of 18 months, the estimated 2-year overall and event-free survival was 64.8% (95% confidence interval: 47.8%-86.7%) and 58.4% (95% CI: 41.9%-81.7%), respectively. The 2-year cumulative incidence rate of relapse was 19.5% (95% CI: 9.0%-35.8%), whereas the non-relapse mortality rate was 21.8% (95% CI: 11.3%-38.1%). These results demonstrated the feasibility of PT-Cy as GVHD prophylaxis in this clinical setting. This strategy could significantly reduce the incidence of chronic GVHD and its moderate to severe forms but not of acute GVHD and results in similar survival outcomes compared with the historical group. A prospective study with additional patients is warranted to confirm the role of PT-Cy in lymphoid malignancy.

Peripheral blood stem cell transplantation from HLA-mismatched unrelated donor or haploidentical donor for the treatment of X-linked agammaglobulinemia / 中国当代儿科杂志

Allogeneic stem cell transplantation (allo-SCT) is currently the only curative option for patients with X-linked agammaglobulinemia (XLA). In this study, patient 1 aged 4 years who underwent allogeneic peripheral blood stem cell transplantation (allo-PBSCT) from HLA-mismatched unrelated donor; patient 2 aged 24 years (childhood onset) with primary cutaneous acral CD8 T cell lymphoma who underwent allo-PBSCT from haploidentical relative donor. Both were treated by reduced toxicity myeloablative conditioning with post-transplantation cyclophosphamide (PTCy), anti-thymocyte globulin (ATG), methotrexate (MTX) and cyclosporine (CsA) for graft-versus-host-disease (GVHD) prophylaxis. In patient 1, neutrophil and platelet engraftment were observed on day 11 post-transplantation; the donor chimerism dropped on day 90 post-transplantation, and recovered on day 150 with donor lymphocyte infusion (DLI). In patient 2, neutrophil and platelet engraftment were observed on days 20 and 87 post-transplantation respectively, with complete donor chimerism on day 30 post-transplantation. The serum levels of IgG, IgM and IgA and the percentage of CD19 B cells in peripheral blood of patients 1 and 2 returned to normal within 2 months and more than 1 year after transplantation respectively. There was no evidence of acute GVHD for the two patients. Patient 1 developed a limited type of skin chronic GVHD after DLI, which disappeared after anti-GVHD treatment. This is the first report of successful treatment for two XLA patients using PTCy with allo-PBSCT from HLA-mismatched unrelated donor or haploidentical donor, combining with improved conditioning, which expands the pool of eligible donors for patients with XLA.

Influencing Factors and Prevation of Infection in Leukemia Patients after Allogeneic Peripheral Blood Stem Cell Transplantation / 中国实验血液学杂志

OBJECTIVE@#To explore the influencing factors and countermeasures of infection in leukemia patients after allogeneic peripheral blood hematopoietic stem cell transplantation.@*METHODS@#A total of 126 patients with leukemia admitted in our hospital from August 2016 to March 2018 were selected. The number of infected patients after transplantation was recorded, and the causes of infection were analyzed.@*RESULTS@#Among the 126 patients, 43 were positive for infection, and the infection rate was 34.13%. A total of 89 pathogens were detected, of which bacteria accounted for 64.05%; virus accounted for 22.47%, and fungi accounted for 13.48%. The patient's age, donor type, pre-transplant infection, prophylactic use of antibiotics and aGVHD all were factors influencing the patient's infection (P＜0.05). The follow-up results showed that the incidence of infection in the intervention group significantly decreased after intervention with prevention program (P＜0.05). After reasonable nursing intervention, the incidence of infection in the intervention group after follow-up for 12 months was lower than that in the control group (P＜0.05).@*CONCLUSION@#Pre-transplant infection and prophylactic use of antibiotics are factors influencing the infection after allogeneic hematopoietic stem cell transplantation. The incidence of infection can be reduced by reasonable infection prevention.

A Case of Donor Cell Leukemia after Allogenic Peripheral Blood Stem Cell Transplantation for Acute Promyelocytic Leukemia with PML-RARA

Caso Clínico: Citopénia Autoinmune como complicación inmunológica de Trasplante Alogénico de Donante no emparentado, en paciente pediátrico con Anemia Drepanocítica / Clinical Case: Autoimmune Cytopenia as an immunological complication of Allogeneic Unrelated Donor Transplantation, in a pediatric patient with Sickle Cell Anemia

Introducción: La enfermedad de células falciformes es una condición heredada en la quese produce una hemoglobina anómala que desfavorece a la oxigenación tisular, crisis vaso-oclusivas y reacciones hemolíticas. Los pacientes con esta enfermedad presentan una activación anómala de la vía del complemento llevándolos al aumento en frecuencia de infecciones y enfermedades autoinmunes. Presentamos un caso de asociación de una enfermedad autoinmune en un paciente con enfermedad de células falciforme. Caso clínico: Niño de 10 años con Anemia drepanocítica (2009) con esplenectomía y crisis veno-oclusivas recurrentes, fue sometido a trasplante Alogénicoen abril del 2019fuera de la institución con donante isogrupo O+ no emparentado (10/10). Tratado con: Fludarabina ­Busulfan, Timoglobulina+ y Metotexate. Desarrolló Bicitopenia autoinmune y síndrome febril al día +165 post TPH. Glóbulos blancos: 360 uL, neutrófilos: 14 %, hemoglobina: 7.90 g/dL, plaquetas: 25000 uL, ferritina: 4695 ng/ml, IgG total: 9.88 gr/l, LDH: 190 UI/l. Proteína C reactiva: 2.79 mg/dL, Procalcitonina 0.13 ng/mL. Evolución: posterior a descartar infección viral, se completó un tratamiento antibiótico de amplio espectro y se realizó la suspensión del tratamiento inmunosupresor por sospecha de toxicidad, sin respuesta. Se realizó un estudio medular por citometría de flujo determinando una disminución de la línea linfoide B, y se concluye Citopenia Autoinmune como complicación inmunológica del trasplante. Desenlace: recibióterapia transfusional (plaquetoféresis + glóbulos rojos concentrados). Se utilizó metilprednisolona IV por 3 días y prednisona 30 mg por 14 días con reducción posterior gradual para inicio de Rituximab y ciclosporina. Se completó el tratamiento con Imnunoglobulina 6g IV por 5 días. Al alta glóbulos blancos: 5080 uL, neutrófilos: 67%, hemoglobina: 9.20 g/dL, plaquetas: 20000 uL, después de 18 días de ingreso hospitalario. Conclusión: Los resultados con el tratamiento en este caso sugieren que puede serrazonable considerar las citopeniasautoinmunes como una manifestación hematológica diagnóstica de la EICH crónica. Alternativamente, es posible que el tratamiento de citopenia inmune con esteroides, Rituximab y otros inmunosupresores

Introduction: Sickle cell disease is an inherited condition in which an abnormal hemoglobin is produced that impairs tissue oxygenation, vaso-occlusive crises and hemolytic reactions. Patients with this disease present an abnormal activation of the complement pathway, leading to an increase in the frequency of infections and autoimmune diseases. We present a case of association of an autoimmune disease in a patient with sickle cell disease. Clinical case:10-year-old boy with sickle cell anemia (2009) with splenectomy and recurrent veno-occlusive crisis, underwent Allogeneic transplantation in April 2019 outside the institution with an unrelated isogroup O + donor (10/10). Treated with: Fludarabine -Busulfan, Thymoglobulin + and Metotexate. He developed autoimmune bicytopenia and febrile syndrome at +165 day post HSCT. White blood cells: 360 uL, neutrophils: 14%, hemoglobin: 7.90 g / dL, platelets: 25,000 uL, ferritin: 4695 ng / ml, total IgG: 9.88 gr / l, LDH: 190 IU/l. C-reactive protein: 2.79 mg/dL, procalcitonin 0.13 ng / mL. Evolution:after ruling out viral infection, the patient completed a broad-spectrum antibiotic treatment and underwent suspension of immunosuppressive treatment due to suspected toxicity, with no response. A medullary study by flow cytometry was performed, determining a decrease in the B lymphoid line, and autoimmune cytopenia was concluded as an immunologicalcomplication of the transplant. Outcome:The patient received transfusion therapy (plateletpheresis + concentrated red blood cells). He also received IV methylprednisolone for 3 days and 30 mg prednisone for 14 days with gradual subsequent reduction to start Rituximab and cyclosporine. The treatment with Immunoglobulin 6g IV for 5 days was completed. At discharge, white blood cells: 5080 uL, neutrophils: 67%, hemoglobin: 9.20 g / dL, platelets: 20,000 uL, after 18 days of hospital admission. Conclusion:The results with treatment in this case suggest that it may be reasonable to consider autoimmune cytopenias asa diagnostic hematological manifestation of chronic GVHD. Alternatively, it is possible to treat immune cytopenia with steroids, rituximab, and other immunosuppressants

Efficacy Analysis of Unrelated Cord Blood Transplantation for High-Risk Refractory AML1-ETO Positive Myeloid Leukemia / 中国实验血液学杂志

OBJECTIVE@#To analyze the clinical outcomes of engraftment, graft-versus-host disease (GVHD) and survival in the patients with AML1-ETO positive acute myeloid leukemia (AML) treated with unrelated umbilical cord blood transplantation (UCBT).@*METHODS@#Forty-Five patients with high-risk refractory AML1-ETO positive AML were treated with a single UCBT in a single center from July 2010 to April 2018. All the patients underwent a myeloablative preconditioning regimen，and cyclosporine A (CSA) combined with mycophenolate mofetil (MMF) was used to prevent GVHD.@*RESULTS@#The median value of total nucleated cells (TNC) in cord blood was 5.21 (1.96-12.68)×10/kg recipient body weight, and that of CD34+ cells was 5.61 (0.56-15.4)×10/kg recipient weight. The implantation rate of neutrophil at 42 d and that of platelet at 120 d were 95.6% and 86.7%, respectively. The median time of absolute neutrophil count (ANC)＞0.5×10/L and platelet 20×10/L were 16 (12-18) d and 37 (17-140) d after transplantation, respectively. The cumulative incidence of Ⅰ -Ⅳ grade acute GVHD (aGVHD) at 100 d after transplantation was 48.9% (95% CI 33.5%-62.6%), Ⅱ-Ⅳ grade aGVHD occurred in 12 cases (33.3%) (95% CI 20%-47.2%) , and Ⅲ-Ⅳ grade a GVHD in 8 cases (20%) (95% CI 9.8% -32.8%). In 5 cases of 40 patients survived over 100 days, the chronic GVHD (cGVHD) occurred after transplantation, among which 4 were localized, and 1 was extensive. 3 patients relapsed, and the 2-year cumulative relapse rate was 9.5% (95% CI 2.4%-22.8%). The median follow-up time was 23.5 (0.9-89.67) months, 10 patients died, 2-year disease-free survival rate (DFS) was 72.7%, and overall survival rate (OS) was 75.5%. Multivariate analysis showed that Ⅲ-Ⅳ. acute GVHD (aGVHD) affected overall survival.@*CONCLUSION@#UCBT is an effective rescue treatment for patients with high-risk refractory AML1-ETO positive AML.

Differential impact of anti-thymocyte globulin dosing by disease risk index in alternative donor peripheral blood stem cell transplantation in patients with acute leukemia or myelodysplastic syndrome after reduced intensity conditioning

No abstract available.

Successful engraftment after infusion of multiple low doses of CD34+ cells from a poorly matched sibling donor in a patient with severe aplastic anemia / 영남의대학술지

The dose of CD34+ cells is known to influence the outcome of allogeneic peripheral blood stem cell (PBSC) and/or T-cell-depleted transplantation. A previous study proposed that 2×10⁶ CD34+ cells/kg is the ideal minimum dose for allogeneic transplantation, although lower doses did not preclude successful therapy. In the case we present here, CD34+ cells were collected from a matched sibling donor on the day of allogeneic hematopoietic stem cell transplantation; however, the number of cells was not sufficient for transplantation. Consequently, PBSCs were collected three additional times and were infused along with cord blood cells from the donor that were cryopreserved at birth. The cumulative dose of total nuclear cells and CD34+ cells was 15.9×10⁸ cells/kg and 0.95×10⁶ cells/kg, respectively. White blood cells from this patient were engrafted on day 12. In summary, we report successful engraftment after infusion of multiple low doses of CD34+ cells in a patient with severe aplastic anemia.

Nutritional Intervention for a Patient with Acute Lymphoblastic Leukemia on Allogeneic Peripheral Blood Stem Cell Transplantation

Hematopoietic stem cell transplantation (HSCT) causes many complications such as anorexia, nausea, vomiting, diarrhea, and mucositis. Most patients undergoing HSCT have risk for malnutrition in the process of transplantation so artificial nutrition support is required. The purpose of this case report is to share our experience of applying nutrition intervention during the transplantation period. According to HSCT process, the change of the patient's gastrointestinal symptoms, oral intake and nutritional status was recorded. By encouraging oral intake and providing parenteral nutrition, the patient had only 0.3%, losing weight during the transplantation period. In conclusion, it emphasized that the nutritional status changes during the HSCT period should be closely monitored and nutritional management through appropriate nutritional support and interventions in hospital and after discharge.

Analysis of Curative Efficacy of Different Chemotherapy Regimen Combined with Autologous Peripheral Blood Hematopoietic Stem Cell Transplantation on Multiple Myeloma / 中国实验血液学杂志

OBJECTIVE@#To evaluate the efficacy of autologous peripheral blood hematopoietic stem cell transplantation (auto-PBHSCT) on patients with multiple myeloma( MM) after Sequential different chemotherapy.@*METHODS@#Seven cases of patients with MM were included in the A group, and 14 cases of patients received 4-6 courses of chemotherapy with VAD and MP before transplantation were included in the B group and received 4-6 courses of chemotherapy with VTD and VD before transplantation. Auto-peripheral blood hematopoietic stem cell were mobilized by G-CSF. Condition regimen were melphalan(A group) or bortezomib combined melphalan(B group). IFN-α(A group) or Thalidomide(B group) was used as maintenance treatment after auto-PBHSCT.@*RESULTS@#Two cases of patients reached to complete remission (CR)(2/7,28.6%),1 case got very good partial remission (VGPR) (1/7,14.3%), 4 cases got partial remission(PR) (4/7,57.1%) in A group, and 9 cases got CR (9/14,64.3%), 3 cases got VGPR(3/14,21.4%), and 2 cases got PR(2/14,14.3%) in the B group before auto-PBHSCT. The CR and VGPR were significant difference between 2 groups (P<0.05). All the patients got hematopoietic recovery. In 2 groups, the median time of ANC recovery≥0.5×10/L was 13 (11-16) and 14（11-18）days, that of WBC recovery ≥4.0×10/L were 16(15-19) and 18(16-20)days, Plt recovery ≥ 50 ×10/L was 21 (18-25) and 21(17-25) days. Bone marrow showed CR in 21 to 28 days after transplantation. All of 7 cases of patients remised in 6 to 47 months after transplantation, and 4 cases died lastly and 3 cases failed to be followed up in A group. The median time of progression-free survival(PFS) was 36(6-47) months, and that of overall survival(OS) was 37(7-50) months. In B group, 2 cases of patients remissed in 5 and 17 months after transplantation, and did lastly, 1 case relieved in 12 months after transplantation and failed to be followed up. 1 case of patient relived in 46 months after transplantation, and then received the second auto-PBHSCT, and got CR for 105 months. Other 10 cases got CR, their median time of PFS was 45.5(4-105) months, the median time of overall survival(OS) was 45.5(4-105) months. The PFS and OS were very significant different between 2 groups (P<0.01).@*CONCLUSION@#Bortezomib-based chemotherapy, Auto-PBHSCT and maintenance treatment with thalidomide were favorable to the patients of MM for survival prolongation.

Efficacy and Safety of Unmanipulated Haploidentical Related Donor Allogeneic Peripheral Blood Stem Cell Transplantation in Patients with Relapsed/Refractory Acute Myeloid Leukemia / 中华医学杂志(英文版)

<p><b>Background</b>Studies of haploidentical-related donor (HRD) stem cell transplantation using a combination of peripheral blood stem cells (PBSCs) and bone marrow as the graft have reported encouraging results for patients with hematological diseases. However, few studies specifically reported transplantation of only PBSCs from HRDs among patients with relapsed or refractory acute myeloid leukemia (AML). Here, the long-term outcomes and side effects of unmanipulated HRD PBSC transplantation (HRD-PBSCT) for relapsed/refractory AML were analyzed.</p><p><b>Methods</b>We performed a retrospective analysis of the outcomes in relapsed/refractory AML patients who underwent PBSCT from HRDs (n = 36).</p><p><b>Results</b>Thirty-one (86.1%) patients in the HRD-PBSCT group achieved platelet recovery. The cumulative incidence of acute graft-versus-host disease (aGVHD) in the HRD-PBSCT group was 40.00%, and the cumulative incidence of grades 2-4 aGVHD in this group was 13.33%. A total of 13 patients in the HRD-PBSCT group had recurrent disease at a median of 183 days after transplantation (range: 10-1700 days), reaching cumulative incidences of relapse of 50.28% at 5 years. On multivariate analysis, donor age and patient age >40 years were independent risk factors for inferior disease-free survival or overall survival (P < 0.05). The results of the present study demonstrate rapid and complete neutrophil engraftment, a low incidence of grade 2-4 aGVHD, and promising survival rates in patients after HRD-PBSCT. Thus, granulocyte colony-stimulating factor-primed PBSCs may be a reliable graft source in unmanipulated HRD-HSCT under myeloablative conditioning when no matched sibling donor is available.</p><p><b>Conclusions</b>Our results support the feasibility, effectiveness, and tolerability of PBSCs as a graft source in unmanipulated HRD transplantation under myeloablative conditioning in patients with leukemia.</p>

Living donor liver transplantation prior to multiple myeloma treatment in a patient with hepatitis B-associated hepatocellular carcinoma and liver cirrhosis: a case report

Clinical outcomes of living donor liver transplantation (LDLT) for hepatocellular carcinoma (HCC) in patients with multiple myeloma (MM) have not been established in terms of HCC recurrence and MM deterioration after LDLT. A 51-year-old man with chronic hepatitis B was diagnosed with HCC and MM. Since the patient also had decompensated liver cirrhosis (LC), he underwent LDLT prior to autologous peripheral blood stem cell transplantation (PBSCT) to prevent fulminant hepatitis due to HBV reactivation. The patient received Epstein-Barr virus prophylaxis and a triple immunosuppressive regimen of tacrolimus, everolimus, and steroid after LDLT. Autologous PBSCT was performed 7 months after LDLT. He showed a complete response to treatment of MM without post-LT complications or HCC recurrence. In conclusion, LDLT could be adapted for treatment of MM patients with combined HCC and decompensated LC because it is an effective strategy of preventing HBV reactivation and HCC recurrence after induction therapy of MM.

Effect of Intravenous Infusion of G-CSF-Mobilized Peripheral Blood Mononuclear Cells on Upper Extremity Function in Cerebral Palsy Children

OBJECTIVE: To investigate the effect of intravenous infusion of peripheral blood mononuclear cells (mPBMC) mobilized by granulocyte-colony stimulating factor (G-CSF) on upper extremity function in children with cerebral palsy (CP). METHODS: Fifty-seven children with CP were enrolled. Ten patients were excluded due to follow-up loss. In total, 47 patients (30 males and 17 females) were analyzed. All patients' parents provided signed consent before the start of the study. After administration of G-CSF for 5 days, mPBMC was collected and cryopreserved. Patients were randomized into two groups 1 month later. Twenty-two patients were administered mPBMC and 25 patients received normal saline as placebo. Six months later, the two groups were switched, and administered mPBMC and placebo, respectively. Quality of Upper Extremity Skills Test (QUEST) and the Manual Ability Classification System (MACS) were used to evaluate upper motor function. RESULTS: All subdomain and total scores of QUEST were significantly improved after mPBMC and placebo infusion, without significant differences between mPBMC and placebo groups. A month after G-CSF, all subdomain and total scores of QUEST were improved. The level of MACS remained unchanged in both mPBMC and placebo groups. CONCLUSION: In this study, intravenously infused mPBMC showed no significant effect on upper extremity function in children with CP, as compared to placebo. The effect of mPBMC was likely masked by the effect of G-CSF, which was used in both groups and/or G-CSF itself might have other neurotrophic potentials in children with CP.

Impact of Human Leukocyte Antigen Loci and Haplotypes on Intestinal Acute Graft-versus-host Disease after Human Leukocyte Antigen-matched Sibling Peripheral Blood Stem Cell Transplantation / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>Acute graft-versus-host disease (aGVHD) is a common and severe complication of allogeneic hematopoietic stem cell transplantation (allo-HSCT). Some studies have found that the presence of certain specific human leukocyte antigen (HLA) loci could affect the occurrence of aGVHD. Meanwhile, the impact of HLA haplotypes on aGVHD has been rarely studied. This study aimed to investigate the effects of HLA loci and haplotypes on intestinal aGVHD.</p><p><b>METHODS</b>Totally, 345 consecutive patients undergoing first HLA-matched sibling peripheral blood stem cell transplantation (PBSCT) from February 2004 to June 2013 at Institute of Hematology and Blood Diseases Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, were enrolled in this study. HLA loci and haplotypes of recipients with frequency over 5% were searched and their effects on intestinal aGVHD were investigated. Other important factors including donor age, recipient age, donor-recipient sex combinations, and conditioning regimens were also evaluated using logistic regression. Pure upper gastrointestinal tract aGVHD without diarrhea was excluded because the histological proof was unavailable. The follow-up end-point was 6 months after HSCT.</p><p><b>RESULTS</b>The cumulative incidence of intestinal aGVHD was 19.4%, with 18.0% of the patients classified as classic aGVHD and 1.4% as persistent, recurrent, or late aGVHD. Multivariate analysis showed that HLA-A31 locus (odds ratio [OR] 2.893, 95% confidence interval [CI] [1.054, 7.935], P = 0.039), HLA B40-DR15 (OR 3.133, 95% CI [1.250, 7.857], P = 0.015), and HLA B46-DR9 haplotypes (OR 2.580, 95% CI [1.070, 6.220], P = 0.035), female donor for male recipient (OR 2.434, 95% CI [1.319, 4.493], P = 0.004) were risk factors for intestinal aGVHD.</p><p><b>CONCLUSION</b>The presence of certain HLA loci and haplotypes may influence the occurrence of intestinal aGVHD in PBSCT with HLA-identical sibling donors.</p>

Long-term Outcomes of Autologous Peripheral Blood Stem Cell Transplantation for Refractory Rheumatic Diseases

OBJECTIVE: We investigated the long-term outcomes of autologous peripheral blood stem cell transplantation (PBSCT) to treat refractory rheumatic diseases. METHODS: Patients who underwent PBSCT for refractory rheumatic diseases at our institution between 2002 and 2005 were assessed for outcomes including treatment response, adverse events, damage accrual, and survival at 6 months and last follow-up. RESULTS: Eleven patients, including six with systemic lupus erythematosus (SLE), four with systemic sclerosis (SSc), and one with Still's disease were treated with PBSCT. In SLE patients, two showed complete response, two partial response, and two expired. One patient who expired responded completely two months after transplantation but discontinued treatment by choice and expired at six months due to an SLE flare. Long-term, two patients went into remission without organ damage, one patient went into remission with organ damage, and one had low disease activity with organ damage. Of the four patients with SSc, two showed a complete response, one a partial response, and there was one transplantation-related death at six months. At the last record notation, two remained in remission without relapse and one was lost to follow-up. The Still's disease patient partially responded at six months and was in remission at the last record notation. CONCLUSION: The ten-year survival rate was 70% with a 40% recurrence rate and 20% treatment-related mortality rate.

Diabetes mellitus caused by secondary hemochromatosis after multiple blood transfusions in 2 patients with severe aplastic anemia

Hemochromatosis is an inherited or secondary disorder caused by excessive iron storage leading to multiple organ damage. We describe 2 patients with diabetes mellitus caused by hemochromatosis secondary to multiple blood transfusions due to severe aplastic anemia. Subject 1, who was diagnosed with severe aplastic anemia at 15 years of age, received multiple red blood cell transfusions before he underwent autologous peripheral blood stem cell transplantation (PBSCT) at 22 years of age. At 21 years of age, hyperglycemia was detected with increased hemoglobin A1c and serum ferritin levels, 9.7% and 12,910 ng/mL (normal range, 20–320 ng/mL), respectively. The 24-hour urine C-peptide level was normal with negative antiglutamic acid decarboxylase antibody. Subsequently, metformin and an iron-chelating agent were administered. However, an intensive insulin regimen was necessary 2 years after the onset of diabetes. Subject 2, who was diagnosed with severe aplastic anemia at 2 years of age, received multiple blood transfusions until she underwent haploidentical PBSCT at 13 years of age. At 11 years of age, she developed diabetes mellitus with a high serum ferritin level (12,559.8 ng/mL). She is currently 18 years old and has been treated with an intensive insulin regimen and estrogen/progesterone replacement therapy because of hypogonadotropic hypogonadism. It is presumed that the loss of insulin secretory capacity and insulin resistance played a role in the pathogenesis of diabetes mellitus due to hemochromatosis in these cases.