RESUMO
Sinusoidal obstruction syndrome (SOS) is a life-threatening complication of hematopoietic stem cell transplantation (HSCT), whose diagnostic criteria changed over time to achieve a timelier diagnosis. Recently, pediatric-specific criteria presented by the European Society for Blood and Marrow Transplantation (pEBMT) incorporated transfusion-refractory thrombocytopenia (RT) as an early indicator of SOS in children. However, a comparison of all individual diagnostic parameters belonging to pEBMT and former SOS diagnostic criteria has never been performed. This retrospective study conducted at a pediatric tertiary care hospital analyzed all pediatric HSCT cases diagnosed with SOS among 170 children transplanted from 2009 to 2023. Eleven patients developed SOS during this period (incidence: 11/170, 6.5%). pEBMT, Seattle, and Baltimore criteria were retrospectively applied to the 11 cases and compared, showing that RT was the earliest fulfilled parameter (median onset: 6 d post-HSCT). pEBMT and Seattle criteria identified 11/11 SOS cases, with pEBMT leading to an earlier diagnosis. RT typically manifested before diagnosis, with significantly higher platelet transfusion requirements before diagnosis than after. RT is the earliest satisfied criterion in pediatric SOS and typically occurs in the initial stages of the disease before diagnosis. Further research is needed to identify additional early indicators of pediatric SOS.
RESUMO
The optimal management of hemorrhagic cystitis (HC) in hematopoietic stem cell transplantation (HCT) is debated, both for early onset HC (EOHC) secondary to chemotherapy toxicity and BK Polyomavirus (BKPyV)-related HC, due to the lack of controlled trials, particularly referred to pediatric setting. Actually, clinical practice is mainly based on guidelines of the European Conference on Infections in Leukemia, 6th edition, which considers both adult and pediatric populations but concludes that, despite much progress in understanding the pathogenesis, epidemiology, and risk factors, this complication still represents a disabling unmet clinical need with limited prophylactic and therapeutic options. Additionally, the Guidelines of the American Society of Clinical Oncology define the management of chemotherapeutic toxicity independently from the patients' population. A panel of experts belonging to the Hematopoietic Cell Transplant and Infectious Disease Working Group (WG) of Associazione Italiana di Emato-Oncologia Pediatrica (AIEOP) developed a consensus to define the best practices in prevention, diagnosis, and management of HC in pediatric HCT setting.
Assuntos
Cistite , Transplante de Células-Tronco Hematopoéticas , Humanos , Cistite/terapia , Cistite/etiologia , Cistite/diagnóstico , Cistite/prevenção & controle , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Criança , Hemorragia/terapia , Hemorragia/etiologia , Hemorragia/diagnóstico , Hemorragia/prevenção & controle , Itália , Feminino , Masculino , Adulto , Consenso , Cistite HemorrágicaRESUMO
Living donor (LD) lung transplantation (LT) represents an exceptional procedure in Western countries. However, in selected situations, it could be a source of unique advantages, besides addressing organ shortage. We report a successful case of father-to-child single-lobe LT, because of the complications of hematopoietic stem cell transplantation from the same donor, with initial low-dose immunosuppressive therapy and subsequent early discontinuation. Full donor chimerism was hypothesized to be a mechanism of transplant tolerance, and this postulated immunological benefit was deemed to outweigh the risks of living donation and the possible drawbacks of single compared with bilateral LT. Favorable size matching and donor's anatomy, accurate surgical planning, and specific expertise in pediatric transplantation also contributed to the optimal recipient and donor outcomes. Ten months after LD LT, the patient's steadily good lung function after withdrawal of immunosuppressive therapy seems to confirm the original hypothesis.
Assuntos
Transplante de Células-Tronco Hematopoéticas , Transplante de Pulmão , Humanos , Criança , Doadores Vivos , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Transplante de Células-Tronco Hematopoéticas/métodos , Terapia de ImunossupressãoAssuntos
COVID-19 , Transplante de Células-Tronco Hematopoéticas , Leucemia Mieloide Aguda , SARS-CoV-2/metabolismo , Condicionamento Pré-Transplante , COVID-19/sangue , COVID-19/terapia , Humanos , Lactente , Leucemia Mieloide Aguda/sangue , Leucemia Mieloide Aguda/terapia , Masculino , Transplante HomólogoRESUMO
BACKGROUND: PBSC collection using a blood cell separator in very low weight patients can be frequently complicated by severe adverse effects and technical difficulties. MATERIAL AND METHODS: From March 2013 to January 2017, 14 PBSC collections were performed in 12 children weighing less than 10 kg, affected by different solid tumours. PBSC collection was performed with a "homemade" aseptically assembled circuit. The circuit is composed by a 150 mL collection bag connected with a 4 stopcock ramp, perfused with ACD. This circuit allows collection of a specific total blood amount from CVC, depending on CD34+ /kg target. RESULTS: Mean CD34+ cell performance per collection was 9.3 × 106 /kg. Tolerance to the procedure was very good as none of the patients experienced complications, with the exception of a patient who showed mild cyanosis and pallor after collection. Moreover, no bleeding or thrombotic complications have been observed. To date, 16 PBSC reinfusions have been performed in 7 children with a mean CD34+ cells viability of 98.1% ± 2.7 and mean WBC viability of 57% ± 10. Cell recovery after thawing was 87% ± 10.8. A rapid graft intake for both neutrophils and platelets, between day 7 and 20 after reinfusion was observed. DISCUSSION: The procedure of total blood collection without the use of a cell separator is feasible and allows a good PBSC collection without significant side effects in very low-weight children. Moreover, this method could represent a valid and safe alternative to leukapheresis in patients where classic procedure could be difficult to apply.
Assuntos
Células-Tronco Hematopoéticas , Leucaférese/métodos , Peso Corporal , Feminino , Mobilização de Células-Tronco Hematopoéticas , Humanos , Lactente , MasculinoRESUMO
STAT3 gain-of-function (GOF) mutations can be responsible for an incomplete phenotype mainly characterized by hematological autoimmunity, even in the absence of other organ autoimmunity, growth impairment, or severe infections. We hereby report a case with an incomplete form of STAT3 GOF intensified by a concomitant hereditary hematological disease, which misleads the diagnosis. The patient presented with lymphadenopathy, splenomegaly, hypogammaglobulinemia, and severe autoimmune hemolytic anemia (AIHA) with critical complications, including stroke. A Primary Immune Regulatory Disorders (PIRD) was suspected, and molecular analysis revealed a de novo STAT3 gain-of-function mutation. The response to multiple immune suppressive treatments was ineffective, and further investigations revealed a spectrin deficiency. Ultimately, hematopoietic stem cell transplantation from a matched unrelated donor was able to cure the patient. Our case shows an atypical presentation of STAT3 GOF associated with hereditary spherocytosis, and how achievement of a good long-term outcome depends on a strict clinical and laboratory monitoring, as well as on prompt therapeutic intervention.
Assuntos
Agamaglobulinemia/genética , Anemia Hemolítica Autoimune/genética , Mutação com Ganho de Função , Transtornos Linfoproliferativos/genética , Fator de Transcrição STAT3/genética , Espectrina/deficiência , Agamaglobulinemia/imunologia , Idade de Início , Anemia Hemolítica Autoimune/imunologia , Criança , Ciclosporina/efeitos adversos , Ciclosporina/farmacocinética , Ciclosporina/uso terapêutico , Citocromo P-450 CYP3A/genética , Feminino , Mutação em Linhagem Germinativa , Doença Enxerto-Hospedeiro/tratamento farmacológico , Doença Enxerto-Hospedeiro/etiologia , Transtornos do Crescimento/genética , Transplante de Células-Tronco Hematopoéticas , Humanos , Imunoglobulinas Intravenosas/uso terapêutico , Imunossupressores/uso terapêutico , Transtornos Linfoproliferativos/tratamento farmacológico , Transtornos Linfoproliferativos/imunologia , Mutação de Sentido Incorreto , Polimorfismo de Nucleotídeo Único , Prednisolona/uso terapêutico , Hemorragia Retiniana/induzido quimicamente , Fator de Transcrição STAT3/fisiologia , Espectrina/genética , Doadores não RelacionadosRESUMO
Sinusoidal obstruction syndrome (SOS), also known as veno-occlusive disease (VOD), is a potentially life-threatening complication that may develop after hematopoietic stem cell transplantation (HSCT). The aims of this retrospective multicenter study were to evaluate the incidence of SOS/VOD in a large cohort of children transplanted in centers across Italy by applying the new European Society for Blood and Marrow Transplantation (EBMT) criteria and to analyze the risk factors underlying this complication. We retrospectively reviewed data of pediatric HSCTs performed in 13 AIEOP (Associazione Italiana di Ematologia e Oncologia Pediatrica)-affiliated centers between January 2000 and April 2016. The new pediatric EBMT criteria were retrospectively applied for diagnoses of SOS/VOD and severity grading. Among 5072 transplants considered at risk for SOS/VOD during the study period, 103 children (2%) developed SOS/VOD, and the grade was severe or very severe in all patients. The median time of SOS/VOD occurrence was 17 days after HSCT (range, 1 to 104). Sixty-nine patients (67%) were treated with defibrotide for a median time of 16 days (range, 4 to 104). In multivariable analysis age < 2 years, use of busulfan during the conditioning regimen, female gender, and hemophagocytic lymphohistiocytosis were risk factors statistically associated with the development of SOS/VOD. The overall mortality directly related to SOS/VOD was 15.5%. Overall survival at 1 year was worse in patients with SOS/VOD (Pâ¯=â¯.0033), and this difference disappeared 5 years after HSCT. Nonrelapse mortality was significantly higher 1 and 5 years after transplantation in patients who developed SOS/VOD (P < .001). Based on the application of new EBMT criteria, the overall incidence of SOS/VOD recorded in this large Italian pediatric retrospective study was 2%. Nonrelapse mortality was significantly higher in patients who developed SOS/VOD. Identifying the risk factors associated with SOS/VOD can lead to more effective early treatment strategies of this potentially fatal HSCT complication in childhood.
Assuntos
Transplante de Células-Tronco Hematopoéticas , Hepatopatia Veno-Oclusiva , Polidesoxirribonucleotídeos/administração & dosagem , Sistema de Registros , Aloenxertos , Autoenxertos , Pré-Escolar , Intervalo Livre de Doença , Feminino , Hepatopatia Veno-Oclusiva/diagnóstico , Hepatopatia Veno-Oclusiva/tratamento farmacológico , Hepatopatia Veno-Oclusiva/etiologia , Hepatopatia Veno-Oclusiva/mortalidade , Humanos , Incidência , Lactente , Itália , Masculino , Estudos Retrospectivos , Fatores de Risco , Taxa de SobrevidaRESUMO
BACKGROUND: The incidence of gemcitabine-induced hemolytic uremic syndrome has already been described in adults. Several approaches have been employed in the treatment of gemcitabine-induced hemolytic uremic syndrome with different outcomes. One of the most promising agents is eculizumab, which is a monoclonal antibody directed against C5 complement protein. CASE PRESENTATION: We reported the case of a 3-year-old white boy with medulloblastoma who underwent high-dose chemotherapy and craniospinal irradiation. Afterwards he started maintenance chemotherapy with gemcitabine and oxaliplatin. After five courses he presented a progressive clinical worsening, which resulted in a systemic thrombotic microangiopathy. Initially he was treated with rituximab without clinical improvement. Therefore he started therapy with repeated cycles of eculizumab. After seven infusions he showed a gradual improvement and finally a complete remission of gemcitabine-induced hemolytic uremic syndrome. CONCLUSIONS: Eculizumab prevents serious complement-mediated vascular damage for chemotherapy-induced thrombotic microangiopathy in pediatric cases.
Assuntos
Anticorpos Monoclonais Humanizados/administração & dosagem , Antimetabólitos Antineoplásicos/efeitos adversos , Inativadores do Complemento/administração & dosagem , Desoxicitidina/análogos & derivados , Síndrome Hemolítico-Urêmica/tratamento farmacológico , Neoplasias Cerebelares/tratamento farmacológico , Pré-Escolar , Desoxicitidina/efeitos adversos , Evolução Fatal , Síndrome Hemolítico-Urêmica/induzido quimicamente , Síndrome Hemolítico-Urêmica/diagnóstico , Humanos , Masculino , Meduloblastoma/tratamento farmacológico , GencitabinaRESUMO
RB is a primarily pediatric cancer arising from the retina, initiated by biallelic loss of the RB1 gene. We report five children with bilateral RB (n = 3), extra-ocular disseminated RB, or disseminated relapsed RB, who were treated with tandem high-dose chemotherapy and autologous stem cell rescue. All patients received at least 2.2 × 10(6) /kg CD34(+) (median, 3.9 × 10(6) /kg) cells. The preparative regimen for course 1 was carboplatin, thiotepa, etoposide, and for course 2, CM and melphalan. ANC of at least 0.5 × 10(9) /L occurred at a median of 11 days (range, 10-12) and 15 days (range, 12-16) after the first and second procedure, respectively. Platelet engraftment occurred at a median of 13 days (range, 12-17) and 15 days (range, 14-22) after the first and second procedure, respectively. All of the five patients treated remain alive and disease free at the last follow-up time, ranging between 21 and 44 months after completion of autologous transplant. Additional therapy was required in one patient, in whom enucleation had to be performed because of early disease relapse, refractory to local therapy. Intensification of chemotherapy with repeated high-dose chemotherapy and autologous rescue appears an acceptable choice in selected cases with bilateral or extra-ocular disease, either recurrent or refractory.
Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Transplante de Células-Tronco Hematopoéticas , Retinoblastoma/terapia , Pré-Escolar , Terapia Combinada , Feminino , Humanos , Masculino , Transplante AutólogoRESUMO
BACKGROUND: Peripheral blood stem cells (PBSCs) are the preferred source in autologous transplantation. We assessed prospectively the efficacy of mobilization in pediatric patients and risk factors associated with its failure. STUDY DESIGN AND METHODS: Patients, aged 0 to 17 years, needing a first collection of PBSCs for autologous stem cell transplantation were eligible. The study period was from July 2008 to September 2010. A blood peak of fewer than 20 × 10(6) CD34+ cells/L was used as the cutoff to define a poor mobilizer. RESULTS: A total of 145 patients, 57% male (82) and 43% female (63), with a median age of 7 years, affected by solid tumor, 79% (114), and acute leukemia or lymphoma, 21% (31), were enrolled. Granulocyte-colony-stimulating factor used was filgrastim in 69%, lenograstim in 26%, and pegfilgrastim in 5% of patients. A total of 83% (121) of patients mobilized successfully, the median CD34+ count being 120 × 10(6) /L (range, 23 × 10(6) -1840 × 10(6) /L). A single leukapheresis procedure was sufficient to achieve the target CD34+ cell dose in 82% (99/121) of patients. Among 24 poor mobilizer patients, 15 underwent a second mobilizing course and nine required a marrow harvest. Factors associated with poor mobilization were metastatic disease and relapse. Among 99 patients who underwent autologous stem cell transplantation, the median times to neutrophil and platelet engraftment and of hospitalization were longer by 2, 12, and 6 days in poor versus good mobilizer group. CONCLUSIONS: In pediatric patients undergoing a first mobilization, the incidence of poor mobilization was 17%. Failure of mobilization resulted in an increase in health costs and a longer hospitalization for those who underwent autologous stem cell transplantation.
Assuntos
Mobilização de Células-Tronco Hematopoéticas , Neoplasias/terapia , Adolescente , Antígenos CD34/análise , Criança , Pré-Escolar , Feminino , Mobilização de Células-Tronco Hematopoéticas/efeitos adversos , Transplante de Células-Tronco Hematopoéticas , Humanos , Lactente , Recém-Nascido , Masculino , Estudos Prospectivos , Fatores de Risco , Transplante AutólogoRESUMO
BACKGROUND: Controlled-rate freezing (CRF) followed by storage in liquid nitrogen is employed by most centers as the standard procedure for peripheral blood progenitor cell (PBPC) cryopreservation. Uncontrolled-rate freezing (URF) at -80 degrees C is more simple, time-saving, less expensive, and, possibly, as effective as CRF. The aim of this retrospective analysis was to compare CRF and URF in childhood transplantation. STUDY DESIGN AND METHODS: A total of 54 PBPC transplants performed in 39 children aged 3 to 16 years (median, 9.5 years) were analyzed: 23 transplants in 16 children with CRF versus 31 transplants performed in 23 children with -80 degrees C URF. All grafts contained at least 2 x 10(6) per kg unselected CD34+ cells, enumerated before freezing. Nucleated cells infused ranged from 1.32 x 10(8) to 4.3 x 10(8) per mL with a median of 3.1 x 10(8) per mL. Cryoprotectant solution consisted of a final dimethyl sulfoxide (DMSO) concentration of 10 percent DMSO with autologous plasma. RESULTS: The two study groups did not differ in terms of timing of neutrophil and platelet recovery or transfusion requirements. Adverse events related to graft infusion, severe complications, and transplant-related mortality were not significantly different between CRF and URF groups. In both groups only mild adverse events were observed during graft administration. URF procedures, however, were simpler and less expensive. At a median follow-up of 72 months, no secondary myelodysplasia was observed in either group. CONCLUSION: Our analysis suggests that URF is safe and effective in the pediatric population.
Assuntos
Preservação de Sangue/métodos , Criopreservação/métodos , Transplante de Células-Tronco de Sangue Periférico/métodos , Adolescente , Criança , Pré-Escolar , Feminino , Seguimentos , Humanos , Masculino , Reprodutibilidade dos Testes , Resultado do TratamentoRESUMO
BACKGROUND: Leukapheresis procedures require adequate flow rates, which in children may frequently involve invasive vascular access placement. STUDY DESIGN AND METHODS: A minimally invasive peripheral radial artery catheter was used for drawing blood in 85 leukapheresis procedures performed in 33 pediatric patients. Blood return to the patients was provided by either a central Broviac-type catheter or a peripheral venous access. The patients' age range was 1 to 18 years (median, 9.5) and the weight range was 9 to 73 kg (median, 29 kg). Vasocan Braunüle Luer Lock IV cannulas (22 gauge in 78 and 20 gauge in 7) were placed percutaneously under local anesthesia, and in 8 patients, catheter placement was carried out during general anesthesia for other procedures. A continuous flow cell separator was used in all cases (Fresenius AS104 in 23 and AS204 in 62). RESULTS: Flow rates ranged from 18 to 45 mL per minute, the mean number of total blood volumes processed was 2.07 (range, 0.51-2.51), and the mean duration of the procedures was 150 minutes (range, 90-260). The 22-gauge cannulas provided adequate flow rates independently of patient age and weight. No significant thrombotic, embolic, hemorrhagic, ischemic, or infectious complications were observed. CONCLUSION: Peripheral radial artery catheters are safe, are minimally invasive, and provide steady, high-flow rates, and they should be considered for patients requiring leukapheresis and lacking a suitable vascular access for drawing blood.
Assuntos
Cateteres de Demora/normas , Leucaférese/métodos , Artéria Radial , Adolescente , Doenças Autoimunes/terapia , Cateteres de Demora/efeitos adversos , Criança , Pré-Escolar , Feminino , Mobilização de Células-Tronco Hematopoéticas , Humanos , Lactente , Leucaférese/instrumentação , Masculino , Neoplasias/terapia , Transplante de Células-Tronco de Sangue Periférico/métodos , Transplante Autólogo/métodosRESUMO
Specific and sensitive tumor cell detection is becoming increasingly important for diagnosing and staging as well as for the therapeutic management of neuroblastoma patients. We propose a chromogranin A heminested reverse transcription polymerase chain reaction (CgA hn RT-PCR) procedure for the detection of neuroblastoma minimal residual disease in peripheral blood and bone marrow samples. The results were checked in comparison with the presently available procedures (i.e., with the tyrosine hydroxylase nested RT-PCR [TH n RT-PCR] and with the immunocytochemical approach using anti-GD2 antibodies). Controls from healthy patients or from people with unrelated disease (12 samples of bone marrow and 23 samples of peripheral blood) and serial dilution experiments using neuroblastoma cell lines (SKNLP, SKNFI, STA6, STA8) showed CgA hn RT-PCR full specificity and sensitivity ranging from 10(3) to 10(6) (depending on the cell line). The results compared favorably with those obtained using TH n RT-PCR. Preliminary data obtained analyzing bone marrow and peripheral blood specimens from stage IV neuroblastomas showed substantially overlapping results between CgA and TH n RT-PCR procedures. Our data support the potential usefulness of CgA heminested RT-PCR as a specific and sensitive procedure for minimal disease detection in neuroblastoma. A prospective evaluation of this tool in clinical studies might be warranted.
Assuntos
Medula Óssea/enzimologia , N-Acetilgalactosaminiltransferases/sangue , Neuroblastoma/enzimologia , Tirosina 3-Mono-Oxigenase/sangue , Adolescente , Adulto , Biomarcadores Tumorais/sangue , Biomarcadores Tumorais/genética , Medula Óssea/patologia , Criança , Pré-Escolar , Cromogranina A , Cromograninas/sangue , Cromograninas/genética , Feminino , Humanos , Imuno-Histoquímica , Masculino , Monócitos/enzimologia , Monócitos/patologia , N-Acetilgalactosaminiltransferases/imunologia , Neuroblastoma/sangue , Neuroblastoma/patologia , RNA Mensageiro/análise , RNA Mensageiro/sangue , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Sensibilidade e Especificidade , Método Simples-Cego , Células Tumorais Cultivadas , Tirosina 3-Mono-Oxigenase/genéticaRESUMO
The aim of this study was to investigate gene expression changes in disseminated neuroblastoma by cDNA array technique. Three stage IV neuroblastomas and one neuroblastoma cell line (SK-N-FI) were analyzed. Expression profiles were confirmed by semiquantitative RT-PCR and in some instances by Northern blotting. Comparison of expression profiles identified several genes which were highly expressed as well as some which were down-regulated in tumor samples relatively to SK-N-FI cells. The tumors studied lacked N-myc overexpression, while showing up-regulation of basic transcription factors, growth factors and receptors such as NSEP, c-myc binding protein MM1, thymosin beta10 (TMSB10), TNF-R superfamily member 10A (TNFRSF10A) and FZ9. These results suggest that cDNA array technology is a powerful tool to identify a set of genes involved in neuroblastoma genesis and progression. Thus, the sensitive cDNA array may provide new insight into many aspects of pediatric tumors and play crucial role in the administration of adjuvant therapy of patients with neuroblastoma.