RESUMEN
Introduction. The Infrapatellar fat pad (IPFP) represents an emerging alternative source of adipose-derived mesenchymal stem cells (ASCs). We compared the characteristics and differentiation capacity of ASCs isolated from IPFP and SC. Materials and Methods. ASCs were harvested from either IPFP or SC. IPFPs were collected from patients undergoing total knee arthroplasty (TKA), whereas subcutaneous tissues were collected from patients undergoing lipoaspiration. Immunophenotypes of surface antigens were evaluated. Their ability to form colony-forming units (CFUs) and their differentiation potential were determined. The ASCs karyotype was evaluated. Results. There was no difference in the number of CFUs and size of CFUs between IPFP and SC sources. ASCs isolated from both sources had a normal karyotype. The mesenchymal stem cells (MSCs) markers on flow cytometry was equivalent. IPFP-ASCs demonstrated significantly higher expression of SOX-9 and RUNX-2 over ASCs isolated from SC (6.19 ± 5.56-, 0.47 ± 0.62-fold; p value = 0.047, and 17.33 ± 10.80-, 1.56 ± 1.31-fold; p value = 0.030, resp.). Discussion and Conclusion. CFU assay of IPFP-ASCs and SC-ASCs harvested by lipoaspiration technique was equivalent. The expression of key chondrogenic and osteogenic genes was increased in cells isolated from IPFP. IPFP should be considered a high quality alternative source of ASCs.
RESUMEN
Thalassemia-free survival after allogeneic stem cell transplantation (SCT) is about 80-90% with either matched-related or -unrelated donors. We explored the use of a mismatched-related ('haplo- ') donor. All patients received two courses of pretransplant immunosuppressive therapy (PTIS) with fludarabine (Flu) and dexamethasone (Dxm). After two courses of PTIS, a conditioning regimen of rabbit antithymocyte globulin, Flu and IV busulfan (Bu) was given followed by T-cell-replete peripheral blood progenitor cells. GvHD prophylaxis consisted of cyclophosphamide (Cy) on days SCT +3 and +4 (post-Cy), and on day SCT +5 tacrolimus or sirolimus was started together with a short course of mycophenolate mofetil. Thirty-one patients underwent haplo-SCT. Their median age was 10 years (range, 2-20 years). Twenty-nine patients engrafted with 100% donor chimerism. Two patients suffered primary graft failure. Median time to neutrophil engraftment was 14 days (range, 11-18 days). Five patients developed mild to moderate, reversible veno-occlusive disease, while nine patients developed acute GvHD grade II. Only five patients developed limited-chronic GvHD. Projected overall and event-free survival rates at 2 years are 95% and 94%, respectively. The median follow up time is 12 months (range, 7-33 months).
Asunto(s)
Trasplante de Células Madre Hematopoyéticas/métodos , Trasplante de Células Madre de Sangre Periférica/métodos , Trasplante Haploidéntico/métodos , Talasemia beta/terapia , Adolescente , Eliminación de Componentes Sanguíneos , Niño , Preescolar , Supervivencia sin Enfermedad , Supervivencia de Injerto , Trasplante de Células Madre Hematopoyéticas/mortalidad , Hemoglobina E , Homocigoto , Humanos , Inmunosupresores/uso terapéutico , Lactante , Trasplante de Células Madre de Sangre Periférica/mortalidad , Tasa de Supervivencia , Acondicionamiento Pretrasplante/métodos , Trasplante Haploidéntico/mortalidad , Adulto JovenRESUMEN
We investigated the level of minimal residual disease (MRD) in 26 children with B-lineage acute lymphoblastic leukemia (ALL) after intensive induction therapy. A quantitative semi-nested polymerase chain reaction (PCR) detecting the clone-specific rearranged immunoglobulin heavy chain genes was developed to improve sensitivity and specificity of amplification. In all patients, one leukemic cell could be detected in a background of 10(5) normal blood mononuclear cells. All patients investigated were in complete remission at the end of induction therapy as evaluated by morphologic criteria. Nineteen patients (73%) had no detectable residual leukemic cells using the sensitive semi-nested PCR. Seven patients (27%) were PCR positive. Three had a low level (<2 x 10(-5) leukemic cells per bone marrow cell), while four patients had a high level (>2 x 10(5)) of detectable residual leukemic cells. All patients with low or undetectable levels of residual leukemia remained in complete remission at a median of 63 months from diagnosis (range 40-80 months), while all four patients with a high level of residual leukemia subsequently relapsed at a median of 21 months from diagnosis (range 13-37 months). The patient groups with undetectable or low, and high level of MRD did not differ significantly in other clinical or genetic features with prognostic significance. We conclude that the level of MRD at the end of the intensive induction therapy period is predictive of outcome in childhood B lineage ALL. If confirmed by large prospective studies, the level of MRD might be useful in stratifying patients into high and low risk categories.
Asunto(s)
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Neoplasia Residual/diagnóstico , Leucemia-Linfoma Linfoblástico de Células Precursoras/tratamiento farmacológico , Leucemia-Linfoma Linfoblástico de Células Precursoras/patología , Adolescente , Linfoma de Burkitt/tratamiento farmacológico , Linfoma de Burkitt/genética , Linfoma de Burkitt/patología , Niño , Preescolar , Femenino , Humanos , Inmunofenotipificación , Lactante , Masculino , Reacción en Cadena de la Polimerasa , Leucemia-Linfoma Linfoblástico de Células Precursoras/genética , Pronóstico , Inducción de Remisión , Estudios Retrospectivos , Sensibilidad y Especificidad , Resultado del TratamientoRESUMEN
Chloroethylnitrosoureas (CENUs) are commonly used in the treatment of pediatric and adult central nervous system (CNS) tumors. The antitumor activity of CENUs has been hypothesized to be due to an alkylation occurring at the O6-position of guanine in DNA. The DNA repair protein O6-methylguanine-DNA methyltransferase (MGMT) is responsible for the repair of these potentially cytotoxic lesions and may underlie tumor resistance to CENUs. The current study is the largest report of MGMT levels among newly diagnosed pediatric CNS tumors and the only study that has quantitated MGMT by both biochemical and Western immunoblot assays. Our results show a good correlation between the two methods (r = 0.66). Medulloblastoma/primitive neuroectodermal tumor and ependymoma had the highest level of MGMT, followed by high-grade glioma and low-grade glioma. These data may provide a guide to the use of CENUs in the treatment of pediatric CNS tumors.
Asunto(s)
Neoplasias Encefálicas/enzimología , O(6)-Metilguanina-ADN Metiltransferasa/análisis , Adolescente , Adulto , Western Blotting , Neoplasias Cerebelosas/enzimología , Niño , Preescolar , Ependimoma/enzimología , Femenino , Humanos , Lactante , Masculino , Meduloblastoma/enzimología , Tumores Neuroectodérmicos Primitivos/enzimología , Estudios RetrospectivosRESUMEN
Here, we report a case of paediatric beta-thalassaemia major patient who underwent unrelated T cell-non- depleted bone marrow transplantation and developed a complication of autoimmune haemolytic anaemia (AIHA) refractory to corticosteroid and intravenous immunoglobulin therapy. After this child received two doses (375 mg/m2/dose) of rituximab (anti-CD20 monoclonal antibody), his AIHA was resolved.
Asunto(s)
Anemia Hemolítica Autoinmune/etiología , Anemia Hemolítica Autoinmune/terapia , Anemia Refractaria/etiología , Anemia Refractaria/terapia , Anticuerpos Monoclonales/uso terapéutico , Trasplante de Médula Ósea/efectos adversos , Anemia Hemolítica Autoinmune/sangre , Anemia Refractaria/sangre , Anticuerpos Monoclonales de Origen Murino , Preescolar , Humanos , Masculino , Rituximab , Trasplante Homólogo , Talasemia beta/terapiaRESUMEN
Bone marrow transplantation is the only therapeutic option that can eliminate thalassemic disease. Early results indicated that children in class 3 Lucarelli had a much worse outcome because of high nonrejection mortality and high rejection rate. We therefore tried to investigate a nonmyeloablative stem cell transplantation (NST) approach for such a disease in order to reduce mortality and rejection. We report here the case of successful NST in a 10-year-old girl who had class 3 Lucarelli beta-thalassemia major. The conditioning regimen consisted of busulfan, fludarabine, antilymphocyte globulin and total lymphoid irradiation. Her GVHD prophylaxis included mycophenolate mofetil and cyclosporin. The patient had full donor engraftment without acute and chronic GVHD. She is now alive and well and remains disease-free 1 year after transplant.
Asunto(s)
Trasplante de Células Madre Hematopoyéticas/métodos , Quimera por Trasplante , Acondicionamiento Pretrasplante/métodos , Talasemia beta/terapia , Trasplante de Médula Ósea/métodos , Niño , Supervivencia sin Enfermedad , Humanos , Inmunosupresores/administración & dosificación , Masculino , Radioterapia AdyuvanteRESUMEN
SUMMARY: We conducted a study of unrelated donor bone marrow transplantation (BMT) in 11 children with severe thalassaemia. The conditioning regimen consisted of busulphan, cyclophosphamide and antilymphocyte globulin. All received T-cell nondepleted bone marrow. The median marrow-nucleated cell dose was 4.9 x 10(8) /kg (range; 3.5-8.0 x 10(8) /kg). Median time of granulocyte recovery was 16 days (range; 13-21 days), and of platelet recovery was 39 days (range; 14-196). Grade 2-4 acute graft-versus-host disease (GVHD) developed in six patients (54%), and grade 3-4 in one patient (9%). Three (27%) of 11 evaluable patients had chronic GVHD (limited stage). All 11 patients are alive without thalassaemia after a median follow-up time of 397 days (range; 171-814 days). This study lends support to consideration of unrelated donor BMT as an acceptable therapy to cure severe thalassaemia especially in patients who are young and do not yet show irreversible severe complications of iron overload.
Asunto(s)
Trasplante de Médula Ósea/métodos , Histocompatibilidad , Talasemia/terapia , Factores de Edad , Trasplante de Médula Ósea/efectos adversos , Trasplante de Médula Ósea/inmunología , Niño , Preescolar , Supervivencia de Injerto , Enfermedad Injerto contra Huésped , Humanos , Lactante , Sobrecarga de Hierro/etiología , Cinética , Masculino , Talasemia/complicaciones , Talasemia/mortalidad , Donantes de Tejidos , Acondicionamiento Pretrasplante/métodos , Trasplante Homólogo/inmunología , Resultado del TratamientoRESUMEN
Recombinant activated factor VII (rFVIIa) was given to three children with acute bleeding resulting from liver failure and disseminated intravascular coagulation. Cases I and II (girls aged 3 years and 6 years, respectively) were diagnosed with Dengue hemorrhagic fever and prolonged shock. Case III, a boy aged 9 months, underwent left lobe hepatectomy for a hepatoblastoma, during which 60% of his liver was removed. This case was complicated by myoglobinuria, liver and renal impairment and early disseminated intravascular coagulation. All three patients exhibited active bleeding. Cases I and II received rFVIIa combined with other blood component replacement, while Case III received rFVIIa as the only hemostatic agent. A bolus of 40-180 microg/kg b.w. was administered followed by 16.5-33 microg/kg b.w. per h continuous infusion. As a result, bleeding was controlled, the prothrombin time was shortened and FVII clotting activity was significantly increased. In conclusion, rFVIIa has shown some efficacy in controlling acute bleeding in children with liver failure and disseminated intravascular coagulation.
Asunto(s)
Coagulación Intravascular Diseminada/complicaciones , Factor VIIa/administración & dosificación , Hemorragia/tratamiento farmacológico , Hemorragia/etiología , Fallo Hepático/complicaciones , Enfermedad Aguda , Coagulación Sanguínea/efectos de los fármacos , Niño , Preescolar , Femenino , Humanos , Lactante , Masculino , Proteínas Recombinantes/administración & dosificaciónRESUMEN
Wiskott-Aldrich syndrome (WAS), an X-linked recessive disorder, is characterized by primary progressive T cell immunodeficiency, impaired antipolysaccharide antibody production, eczema, and thrombocytopenia. Stem cell transplantation is the only curative therapy. To evaluate the use of allogeneic peripheral stem cell transplantation (PBSCT) in this group of patients, we performed allogeneic PBSCT in two WAS patients (3 and 12 years old). The conditioning regimen consisted of busulfan 4 mg/kg/day for 4 days, and cyclophosphamide 50 mg/kg/day for 4 days. Graft-versus-host disease prophylaxis was consistent with cyclosporin A and methotrexate. Peripheral blood stem cells were collected from their brother donors (6 and 16 years old) by continuous flow leukapheresis after mobilization with granulocyte-colony-stimulating factor at a dose of 7.5 microg/kg/day for 5 days. Both recipients achieved neutrophils engraftment on days 11 and 12. The first patient achieved platelets engraftment on day 30. The second patient did not have platelet count below 20.0 x 10(9)/l during PBSCT procedure. Both did not develop acute or chronic graft-versus-host disease. At present, they are healthy after PBSCT. The follow up time after transplantation is 1,170 days and 269 days, respectively. Allogeneic PBSCT is economically feasible for WAS. The cost of PBSCT in Thailand is 20 to 30% less than bone marrow and cord blood stem cell transplantation. The cost of the transplant procedure for each patient in Thailand is US $ 12,000. This study is the first report of a successful stem cell transplantation in WAS patients in Thailand.
Asunto(s)
Trasplante de Células Madre Hematopoyéticas , Síndrome de Wiskott-Aldrich/terapia , Adolescente , Niño , Preescolar , Supervivencia de Injerto , Enfermedad Injerto contra Huésped/prevención & control , Antígenos HLA , Humanos , Masculino , Tailandia , Acondicionamiento Pretrasplante , Trasplante Homólogo , Síndrome de Wiskott-Aldrich/genética , Síndrome de Wiskott-Aldrich/inmunologíaRESUMEN
We described the successful allogeneic matched sibling bone marrow transplantation (BMT) in a 5-year-old Thai boy in whom osteopetrosis was diagnosed on the basis of anemia, thrombocytopenia, leukoerythroblastosis, sclerotic bone, hepatosplenomegaly, and visual deficit from an encroachment of cranial nerve foramina. The preparative regimen included 4 days of busulfan 4 mg/kg/day, and 4 days of cyclophosphamide 50 mg/kg/day. Complete hematopoietic engraftment and no evidence of graft versus host disease were shown after BMT. Complete hematologic findings were corrected. His hematopoietic chimerism was changed to that of his donor. Post BMT, he has no hepatosplenomegaly. His bone radiographic findings revealed normal after BMT. Bone marrow biopsy showed normalized bone and bone marrow matrix. However, his vision remained impaired. We believe that this is the first case of successful bone marrow transplantation in an osteopetrosis patient in Thailand.
Asunto(s)
Trasplante de Médula Ósea , Osteopetrosis/terapia , Preescolar , Dermatoglifia del ADN , Genotipo , Enfermedad Injerto contra Huésped/prevención & control , Humanos , Recuento de Leucocitos , Masculino , Neutrófilos/citología , Quimera por Trasplante , Trasplante HomólogoRESUMEN
Thalassemia is a public health problem in Thailand. Progressive iron overload is the life-limiting complication commonly found in thalassemic patients. The assessment of body iron stores is essential for determining the need and efficacy of iron chelation. The parameters of serum iron, total iron binding capacity (TIBC), and serum ferritin were studied in 79 children with thalassemia diseases. The ages ranged from 1 to 17 years with a mean of 7 years and 10 months. Neither of them had clinical symptoms of hepatitis. The correlation between transferrin saturation (TS = serum iron/TIBC x 100) and serum ferritin was shown in the equation of TS = 10.253 In (ferritin) (r = 0.956, p = 0.000). For example, TS = 70.83 per cent indicates serum ferritin of 1,000 ng/ml. Thus, where serum ferritin is not feasible but serum iron and TIBC are available, TS can be used to estimate the level of serum ferritin. Therefore, the assessment of iron stores and monitoring of iron chelation in thalassemic patients can be effectively achieved.
Asunto(s)
Ferritinas/sangre , Talasemia/sangre , Transferrina/análisis , Adolescente , Niño , Preescolar , Femenino , Humanos , Lactante , MasculinoRESUMEN
Wiskott-Aldrich syndrome (WAS), an X-linked recessive disorder, is characterized by progressive T-cell immunodeficiency. Laboratory findings generally demonstrate reduced response to T-cell mitogens, markedly decreased serum concentration of IgM, and thrombocytopenia with small platelet volume. Allogeneic HLA-matched sibling bone marrow transplantation (BMT) can correct this disorder. We report the usefulness of X-linked polymorphic loci to detect X-allele gene tracking among WAS siblings and chimerism between a pre- and post-allogeneic matched sibling peripheral blood stem cell transplantation (PBSCT). A 3 1/2 year old boy with clinical and laboratory findings consistent with WAS underwent allogeneic matched sibling PBSCT. We used BclI restriction fragment length polymorphism (RFLP) of intron 18 of factor VII gene and MseI RFLP of the 5' flanking region of factor IX gene to detect X-allele gene tracking among siblings and family members and chimerism in patients between pre-and post-allogeneic matched sibling PBSCT. We were able to demonstrate that determination of BclI and MseI RFLP can be employed to recognize the difference in X-allele genes between the recipient and donor for allogeneic matched sibling PBSCT. The authors also were able to demonstrate that these polymorphic loci can detect full chimerism of donor hematopoietic cells in recipient blood after allogeneic PBSCT. This finding was correlated with improvement of post-PBSCT clinical and laboratory findings. BclI and MseI RFLP associated with X-chromosome can effectively track X-allele, detect carrier state, and demonstrate the different X-allele among male siblings, and chimerism of hematopoietic cells between donors and recipients in a setting of allogeneic matched sibling BMT or PBSCT for X-linked hereditary diseases such as Wiskott-Aldrich syndrome.
Asunto(s)
Trasplante de Células Madre Hematopoyéticas , Polimorfismo Genético , Síndrome de Wiskott-Aldrich/genética , Síndrome de Wiskott-Aldrich/terapia , Preescolar , Humanos , Masculino , Linaje , Cromosoma XRESUMEN
Subcutaneous portacaths (SQP) placement in 19 pediatric oncology patients were studied. Complications of SQP were evaluated. Two patients had premature SQP removal due to fungal infection and breakage, 1 for each. Two patients had catheter-related bacteremia which was resolved by antibiotic administration. Only 1 patient had occasional difficult blood drawing episodes, because the tip of catheter was inserted through external jugular vein instead of subclavian vein. There were no other serious complications except that some of them had clotted formations, which were resolved easily by urokinase administration. Long-term SQP utilization was possible in 17 of 19 patients, with the average time of 7.5 months. Few complications occurred in the group of patients studied. SQP improved quality of medical care and significantly lessened the anxiety of patients who need long-term chemotherapy treatment. Therefore, placement of the intravenous access device is feasible for pediatric oncology patients in Thailand. The patients are no longer suffering from repeated venipunctures. Although it is expensive, it is convenient and useful for some patients with relatively high socioeconomic status. It should be considered for every pediatric cancer patient who needs prolonged chemotherapy and who has affordable means.
Asunto(s)
Antineoplásicos/administración & dosificación , Catéteres de Permanencia , Neoplasias/tratamiento farmacológico , Humanos , TailandiaRESUMEN
There have been no recommendations for revaccination with the Japanese encephalitis (JE) vaccine in post-hematopoietic stem cell transplantation (HSCT) patients. This study aimed to measure the immunogenic response to a live-attenuated JE vaccine (SA 14-14-2) in post-HSCT patients. JE-specific neutralizing Ab titers were measured before and after the JE vaccination. The patients with Ab titers <10 at the 3-month time point received a second injection at 6 months. A total of 28 patients (male:female=11:17) with a median age of 13 years (4-21 years) were included. The underlying diseases were thalassemia (50%) and hematologic malignancies (50%). Ten patients (35.7%) had Ab titers above the preventive level before vaccination. Nine of 18 patients (50%) seroconverted at 3 months after a single JE vaccination, but only three of these patients had sustained protective Ab levels. Seven of nine patients (78%) seroconverted at 3 months after a second JE vaccine injection, and all of these patients sustained protective Ab levels at 12 months. In conclusion, post-HSCT patients had low seroconversion rates after a single dose of the live-attenuated JE vaccine. These patients may require at least two doses of the JE vaccine to ensure protective Ab levels.
Asunto(s)
Encefalitis Japonesa/terapia , Trasplante de Células Madre Hematopoyéticas/efectos adversos , Vacunas contra la Encefalitis Japonesa/metabolismo , Acondicionamiento Pretrasplante/efectos adversos , Vacunas Atenuadas/inmunología , Adolescente , Niño , Preescolar , Femenino , Humanos , Japón , MasculinoRESUMEN
INTRODUCTION: This is the first pilot study to screen multiple common genetic aberrations in B-cell precursor acute lymphoblastic leukemia (BCP-ALL). METHODS: Thirty-two children with BCP-ALL were investigated for chromosomal rearrangements using interphase fluorescence in situ hybridization (FISH). Eight common translocations and rearrangements, including ETV6-RUNX1, TCF3-PBX1, BCR-ABL1, ETV6, TCF3, MLL, IGH@, and PAX5, were tested for using dual-color DNA probes. RESULTS: ETV6-RUNX1 was the most frequent translocation detected in 11 children (34.4%). Two patients with BCR-ABL1 (6.3%) and one with TCF3-PBX1 (3.1%) translocations were also observed. Using break-apart probes, 11 children (34.4%) had a positive FISH result for ETV6, two patients for IGH@ (6.3%), one patient for MLL (3.1%), and one patient for PAX5 rearrangements (3.1%). All patients with the ETV6-RUNX1 fusion were also identified by split signals for ETV6. Other abnormalities, including extra copies and deletion of genes, were observed within the range of 3.1-34.4%. Cytogenetics analysis showed a single case each of BCR-ABL1 fusion, MLL, and IGH@ rearrangements (3.1% each). ETV6-RUNX1 fusion and ETV6 split-apart rearrangements were not visible by cytogenetics. Likewise, one each of cases with TCF3-PBX1 fusion and with PAX5 split signal seen by FISH was not visible by cytogenetics. CONCLUSION: By using 8 FISH probes in conjunction cytogenetics for the detection of common aberrations, interphase FISH enhanced the detection of chromosomal rearrangements in children with BCP-ALL.