BACKGROUND AND OBJECTIVES: Cardiovascular complications are the leading cause of morbidity and mortality in childhood cancer survivors. Hematopoietic stem cell transplantation (HSCT) is a curable therapy for pediatric cancer. However, changes in cardiac function in children after HSCT are not well known. We assessed left ventricular (LV) function in children after HSCT using speckle tracking echocardiography (STE). SUBJECTS AND METHODS: Forty consecutive patients with median age of 11.9 years (range, 1.5-16 years) who received HSCT for acute leukemia and had comprehensive echocardiography before and after (median 9.2 month) HSCT were included in this study. The LV function parameters including conventional tissue Doppler imaging (TDI) and STE data were collected from pre- and post-HSCT echocardiography. These data were compared to those of 39 age-matched normal controls. RESULTS: Compared to normal controls, post HSCT patients had similar (p=0.06) LV ejection fraction. However, the following three LV function parameters were significantly decreased in post HSCT patients: rate-corrected velocity of circumferential fiber shortening (p=0.04), mitral inflow E velocity (p<0.001), and mitral septal annular E' velocity (p=0.03). The following four STE parameters were also significantly decreased in post HSCT patients: LV global circumferential systolic strain (p<0.01), strain rate (SR, p=0.01), circumferential diastolic SR (p<0.01), and longitudinal diastolic SR (p<0.001). There was no significant change in TDI or STE parameters after HSCT compared to pre-HSCT. Patients with anthracycline cumulative dose >400 mg/m2 showed significantly (p<0.05) lower circumferential systolic strain and circumferential diastolic SR. CONCLUSION: Subclinical cardiac dysfunction is evident in children after HSCT. It might be associated with pre-HSCT anthracycline exposure with little effect of conditioning regimens. Serial monitoring of cardiac function is mandatory for all children following HSCT.
Case-Control Studies* ; Child* ; Echocardiography* ; Hematopoietic Stem Cell Transplantation* ; Humans ; Leukemia* ; Mortality ; Stem Cell Transplantation ; Survivors ; Ventricular Dysfunction, Left*

High-dose cytotoxic therapy followed by autologous stem cell transplantation has been proposed as a novel treatment modality for severe autoimmune disease. The rationale of autologous stem cell transplantation in autoimmune diseases has been based on the autoimmune animal models that marked improvement or complete eradication of autoimmune disease after syngeneic marrow transplantation. In addition, several clinical data showed that allogeneic marrow transplantation has been reported to eradicate concurrent autoimmune disease, suggesting that high-dose cytotoxic therapy may be sufficient to eradicate autoaggressive lymphocytes. Peripheral blood stem cell transplantation is widely used compared to bone marrow transplantation due to rapid marrow recovery and less treatment-related mortality. Recently, immunoablative high-dose cytotoxic therapy without stem-cell rescue also can induce complete remission in patients with refractory, severe autoimmune disease. Although several clinical data of autologous stem transplantation can achieve durable remission in severe autoimmune disease, long-term efficacy has not been fully determined yet. Further studies are needed to assess the exact role of stem cell transplantation in the treatment of severe autoimmune disease through well-designed clinical trials.
Autoimmune Diseases* ; Bone Marrow ; Bone Marrow Transplantation ; Drug Therapy* ; Humans ; Lymphocytes ; Models, Animal ; Mortality ; Peripheral Blood Stem Cell Transplantation ; Stem Cell Transplantation* ; Stem Cells*

China ; Graft Survival ; HLA Antigens ; genetics ; Haplotypes ; Hematopoietic Stem Cell Transplantation ; methods ; mortality ; Humans ; Transplantation, Homologous

Allogenic hematopoietic stem cell transplantation is one of the effective therapy for several hematologic malignancies. Transplantation preparative regimen is designed to eradicate the patient's underlying disease and immunosuppress the patient adequately to prevent rejection of donor's hematopoietic stem cells. so, Conventional myeloablative preparative regimens with high-dose chemotherapy or radiotherapy are related to high rate of morbidity and mortality. however, It has become clear that the high-dose therapy dose not eradicate the malignancy in some patients, and that the therapeutic benefit of allogenic transplantation is largely related to graft-versus-leukemia/graft-versus-tumor (GVL/GVT) effect. An new approach is to utilize less toxic, nonmyeloablative preparative regimens to achieve engraftment and allow GVL/GVT effects to developed. This strategy reduces the risk of treatment-related mortality and allows transplantation for elderly and those with comorbidities that preclude high-dose chemoradiotherapy.
Aged ; Chemoradiotherapy ; Comorbidity ; Drug Therapy ; Hematologic Neoplasms ; Hematopoietic Stem Cell Transplantation ; Hematopoietic Stem Cells ; Humans ; Mortality ; Radiotherapy ; Stem Cell Transplantation* ; Stem Cells*

Allogenic hematopoietic stem cell transplantation is one of the effective therapy for several hematologic malignancies. Transplantation preparative regimen is designed to eradicate the patient's underlying disease and immunosuppress the patient adequately to prevent rejection of donor's hematopoietic stem cells. so, Conventional myeloablative preparative regimens with high-dose chemotherapy or radiotherapy are related to high rate of morbidity and mortality. however, It has become clear that the high-dose therapy dose not eradicate the malignancy in some patients, and that the therapeutic benefit of allogenic transplantation is largely related to graft-versus-leukemia/graft-versus-tumor (GVL/GVT) effect. An new approach is to utilize less toxic, nonmyeloablative preparative regimens to achieve engraftment and allow GVL/GVT effects to developed. This strategy reduces the risk of treatment-related mortality and allows transplantation for elderly and those with comorbidities that preclude high-dose chemoradiotherapy.
Aged ; Chemoradiotherapy ; Comorbidity ; Drug Therapy ; Hematologic Neoplasms ; Hematopoietic Stem Cell Transplantation ; Hematopoietic Stem Cells ; Humans ; Mortality ; Radiotherapy ; Stem Cell Transplantation* ; Stem Cells*

Persistent bone marrow aplasia after intensive chemotherapy is uncommon, but is one of the fatal complications in patients with acute myeloid leukemia (AML). Although allogeneic hematopoietic stem cell transplantation (HSCT) is considered to be contraindicated for patients who have hematologic diseases with serious infections, such as bacterial septicemia or invasive fungal diseases, combined with prolonged neutropenia due to frequent morbidity and mortality, such risks can be overcome by non-myeloablative conditioning and best supportive care. Here, we report an AML patient with persistent marrow aplasia after induction therapy, treated successfully with reduced-intensity allogeneic HSCT despite severe bacterial and fungal infections.
Anemia, Aplastic ; Bone Marrow* ; Drug Therapy* ; Hematologic Diseases ; Hematopoietic Stem Cell Transplantation ; Humans ; Leukemia, Myeloid, Acute* ; Mortality ; Neutropenia ; Sepsis ; Stem Cell Transplantation* ; Stem Cells*

PURPOSE: Pulmonary toxicities, including infectious pneumonia (IP) and idiopathic pneumonia syndrome (IPS), are serious side effects of total body irradiation (TBI) used for myeloablative conditioning. This study aimed to evaluate clinical factors associated with IP and IPS following TBI. MATERIALS AND METHODS: Fifty-eight patients with hematologic malignancies who underwent TBI before allogeneic hematopoietic stem cell transplantation between 2005 and 2014 were reviewed. Most patients (91%) received 12 Gy in 1.5 Gy fractions twice a day. Pulmonary toxicities were diagnosed based on either radiographic evidence or reduced pulmonary function, and were subdivided into IP and IPS based on the presence or absence of concurrent infection. RESULTS: Pulmonary toxicities developed in 36 patients (62%); 16 (28%) had IP and 20 (34%) had IPS. IP was significantly associated with increased treatment-related mortality (p = 0.028) and decreased survival (p = 0.039). Multivariate analysis revealed that the risk of developing IPS was significantly higher in patients who received stem cells from a matched unrelated donor than from a matched sibling donor (p = 0.021; hazard ratio [HR] = 12.67; 95% confidence interval [CI], 1.46–110.30). Combining other conditioning agents with cyclophosphamide produced a higher tendency to develop IP (p = 0.064; HR = 6.19; 95% CI, 0.90–42.56). CONCLUSION: IP and IPS involve different risk factors and distinct pathogeneses that should be considered when planning treatments before and after TBI.
Cyclophosphamide ; Hematologic Neoplasms ; Hematopoietic Stem Cell Transplantation ; Humans ; Mortality ; Multivariate Analysis ; Pneumonia ; Risk Factors ; Siblings ; Stem Cell Transplantation ; Stem Cells ; Tissue Donors ; Unrelated Donors ; Whole-Body Irradiation*

PURPOSE: Pulmonary toxicities, including infectious pneumonia (IP) and idiopathic pneumonia syndrome (IPS), are serious side effects of total body irradiation (TBI) used for myeloablative conditioning. This study aimed to evaluate clinical factors associated with IP and IPS following TBI. MATERIALS AND METHODS: Fifty-eight patients with hematologic malignancies who underwent TBI before allogeneic hematopoietic stem cell transplantation between 2005 and 2014 were reviewed. Most patients (91%) received 12 Gy in 1.5 Gy fractions twice a day. Pulmonary toxicities were diagnosed based on either radiographic evidence or reduced pulmonary function, and were subdivided into IP and IPS based on the presence or absence of concurrent infection. RESULTS: Pulmonary toxicities developed in 36 patients (62%); 16 (28%) had IP and 20 (34%) had IPS. IP was significantly associated with increased treatment-related mortality (p = 0.028) and decreased survival (p = 0.039). Multivariate analysis revealed that the risk of developing IPS was significantly higher in patients who received stem cells from a matched unrelated donor than from a matched sibling donor (p = 0.021; hazard ratio [HR] = 12.67; 95% confidence interval [CI], 1.46–110.30). Combining other conditioning agents with cyclophosphamide produced a higher tendency to develop IP (p = 0.064; HR = 6.19; 95% CI, 0.90–42.56). CONCLUSION: IP and IPS involve different risk factors and distinct pathogeneses that should be considered when planning treatments before and after TBI.
Cyclophosphamide ; Hematologic Neoplasms ; Hematopoietic Stem Cell Transplantation ; Humans ; Mortality ; Multivariate Analysis ; Pneumonia ; Risk Factors ; Siblings ; Stem Cell Transplantation ; Stem Cells ; Tissue Donors ; Unrelated Donors ; Whole-Body Irradiation*

Hematopoietic stem cell transplantation has evolved as a central treatment modality for the management of various hematologic malignancies. Despite adequate posttransplantation immunosuppressive therapy, acute GVHD remains a major cause of morbidity and mortality, even for the patients who have received HLA identical sibling grafts. Once established, acute GVHD is difficult to treat, and the best primary treatments such as corticosteroid have shown responses of approximately 50%. Once GVHD becomes steroid-refractory, the chances of survival are slim at best, and the possibility of long-term complications from chronic GVHD is almost always the rule. Many agents are currently being evaluated to treat this malady, including ATG, monoclonal antibodies, pentostatin, denileukin diftitox, etc. We reported here on a case of steroid refractory acute GVHD that was treated with IL-2 and TNF-alpha blocker in myelodysplastic syndrome patient who underwent unrelated allogeneic stem cell transplantation.
Antibodies, Monoclonal ; Hematologic Neoplasms ; Hematopoietic Stem Cell Transplantation ; Humans ; Interleukin-2* ; Mortality ; Myelodysplastic Syndromes* ; Pentostatin ; Siblings ; Stem Cell Transplantation* ; Stem Cells* ; Transplants ; Tumor Necrosis Factor-alpha*

Chronic granulomatous disease (CGD) is a primary immunodeficiency disease caused by impaired phagocytic function. Hematopoietic stem cell transplantation (HSCT) is a definitive cure for CGD; however, the use of HSCT is limited because of associated problems, including transplantation-related mortality and engraftment failure. We report a case of a patient with CGD who underwent successful HSCT following a targeted busulfan and fludarabine reduced-toxicity myeloablative conditioning. Intravenous busulfan was administered once daily for 4 consecutive days (days –8 to –5), and the target area under the curve was 75,000 µg·hr/L. Fludarabine (40 mg/m2) was administered once daily for 6 consecutive days from days –8 to –3. Antithymocyte globulin (2.5 mg/kg/day) was administered from days –4 to –2. The patient underwent successful engraftment and did not have any severe toxicity related to the transplantation. Conditioning with a targeted busulfan and fludarabine regimen could provide a better outcome for HSCT in CGD, with close regulation of the busulfan dose.
Antilymphocyte Serum ; Bone Marrow Transplantation* ; Bone Marrow* ; Busulfan* ; Granulomatous Disease, Chronic* ; Hematopoietic Stem Cell Transplantation ; Humans ; Mortality ; Transplantation Conditioning