RESUMO
The optimal autologous stem cell rescue (HDC-SCR) regimen for children with high-risk neuroblastoma (HR-NBL) is not defined. Carboplatin/etoposide/melphalan (CEM) is the current US standard; however, European data suggest busulfan/melphalan (Bu/Mel) may have less toxicity. Published data regarding toxicities associated with CEM and Bu/Mel are limited. We conducted a single-institution retrospective cohort study of children with HR-NBL who received CEM or Bu/Mel preparative regimens. Toxicity data were analyzed using χ(2) or Fisher's exact, Wilcoxon two-sample or log-rank tests. Sinusoidal obstruction syndrome (SOS) was observed in 7/44 CEM (15.9%) and 5/21 (24%) Bu/Mel patients (P=0.50). Median time to SOS was longer following Bu/Mel than CEM (20 versus 9 days, P=0.02). Pulmonary hypertension (PHTN) was observed in ~20% of children after Bu/Mel and none after CEM (P=0.01). CEM patients had more nephrotoxicity (P=0.001), packed red blood cell (P=0.02) and platelet transfusions (P=0.008), and days on maximum pain support (P=0.0007). Time to engraftment, length of stay, documented infection rates and HDC-SCR-related mortality were similar. Nephrotoxicity and resource utilization associated with cytopenias and mucositis were greater after CEM. Pulmonary toxicities were more severe after Bu/Mel, and increased vigilance for PHTN may be warranted, particularly in children with hypoxemia out of proportion to respiratory distress.
Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/toxicidade , Agonistas Mieloablativos/toxicidade , Neuroblastoma/complicações , Neuroblastoma/tratamento farmacológico , Condicionamento Pré-Transplante/efeitos adversos , Adolescente , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Bussulfano/administração & dosagem , Carboplatina/administração & dosagem , Criança , Pré-Escolar , Estudos de Coortes , Etoposídeo/administração & dosagem , Feminino , Hepatopatia Veno-Oclusiva/induzido quimicamente , Humanos , Hipertensão Pulmonar/induzido quimicamente , Lactente , Nefropatias/induzido quimicamente , Masculino , Melfalan/administração & dosagem , Mucosite/induzido quimicamente , Agonistas Mieloablativos/administração & dosagem , Neuroblastoma/mortalidade , Neuroblastoma/terapia , Pancitopenia/induzido quimicamente , Estudos Retrospectivos , Transplante de Células-Tronco/efeitos adversos , Transplante de Células-Tronco/métodos , Transplante de Células-Tronco/mortalidade , Condicionamento Pré-Transplante/métodos , Condicionamento Pré-Transplante/mortalidade , Adulto JovemRESUMO
We assessed the frequency and outcome of complications associated with hyperleukocytosis in children who had received remission induction therapy for either acute lymphoblastic leukemia (ALL) or acute nonlymphoblastic leukemia (ANLL). Among 234 consecutive patients with a leukocyte count of 100 X 10(9)/L or greater at diagnosis, the frequency of early death was significantly higher in those with ANLL (23% v 5% for patients with ALL, P less than .001). The risk of early death increased with increasing leukocyte count, especially when it exceeded 300 X 10(9)/L in patients with ANLL (P less than .001). Intracerebral hemorrhage occurred in eight (11%) of the ANLL patients and accounted for six of the 17 early deaths; in all but two instances, the complication was associated with coagulopathy. Respiratory failure, presumably from pulmonary leukostasis, resulted in six other early deaths in ANLL patients. By contrast, intracerebral hemorrhage occurred in only two of the ALL patients (1.2%); both had normal coagulation studies, but leukocyte counts greater than 400 X 10(9)/L. Severe metabolic derangements from blast cell lysis accounted for three of the eight early deaths among patients with ALL. Leukapheresis or exchange transfusion effectively lowered the leukocyte counts of all 15 patients who received the procedures. Either method may be preferable to emergency cranial irradiation for preventing the complications of hyperleukocytosis in children with acute leukemia.
Assuntos
Leucemia Linfoide/tratamento farmacológico , Leucemia/tratamento farmacológico , Leucocitose/complicações , Doença Aguda , Injúria Renal Aguda/etiologia , Adolescente , Transtornos da Coagulação Sanguínea/etiologia , Hemorragia Cerebral/etiologia , Criança , Pré-Escolar , Transfusão Total , Humanos , Lactente , Leucaférese , Leucemia/patologia , Leucemia Linfoide/patologia , Leucocitose/mortalidade , Leucocitose/patologia , Pneumopatias/etiologia , Masculino , Doenças Metabólicas/etiologiaRESUMO
Six patients with a myelodysplastic syndrome (MDS) were treated with bone marrow transplantation (BMT) using partially-matched related (3) or unrelated (3) donors. Patients' ages ranged from 7 to 31 years (median, 10 years). Bone marrow karyotype abnormalities were present in five patients included four with monosomy 7 and one with trisomy 8. One patient was in complete remission before transplant; the remaining five had excess of blasts or were undergoing leukemic transformation. Donor, and recipient were mismatched at the DR locus (2), A locus (2), B locus (1), or A and B loci (1). Conditioning included busulfan, cytarabine, cyclophosphamide, methylprednisolone, and total body irradiation. Cyclosporine was started on day -1. Marrows were T-cell depleted using a monoclonal antibody (MoAb) (CD3) and normal rabbit serum. Four patients engrafted routinely. One patient died of aspergillosis before engraftment (day 12) and one patient failed to engraft on first attempt, but engrafted following additional preparation. Median time to neutrophils greater than 500/microL and platelets greater than 25,000/microL were 16 and 19 days, respectively. Acute graft-v-host disease (GVHD) was less than or equal to grade II in all patients. One patient died with recurrent disease (day 257). One patient died at day 515 of pancreatitis and respiratory failure. Three patients are alive and disease-free at 240, 395, and 560 days post-BMT including two patients with unrelated donors. Partially matched T-depleted bone marrow from related or unrelated donors may be effective, and possibly curative therapy for patients with MDS who lack a histocompatibility locus antigen (HLA)-identical sibling donor.
Assuntos
Transplante de Medula Óssea , Síndromes Mielodisplásicas/cirurgia , Adolescente , Adulto , Medula Óssea/imunologia , Criança , Feminino , Doença Enxerto-Hospedeiro/etiologia , Antígenos HLA/análise , Humanos , Cariotipagem , Masculino , Síndromes Mielodisplásicas/imunologia , Síndromes Mielodisplásicas/mortalidadeRESUMO
The records of 25 pediatric patients with mediastinal nonlymphoblastic lymphoma (NLBL) were reviewed. These patients comprise approximately 5% of all patients with non-Hodgkin's lymphoma (NHL) in the pediatric age group. There were 15 females and ten males. The median age was 13.5 years (range, 2 to 19). Most patients presented with symptoms attributable to a large mediastinal mass, and superior vena cava syndrome was a common feature. Disease was localized to the supradiaphragmatic area in 17 patients (71%) at diagnosis. Pathologic review revealed 22 of these lymphomas to be diffuse histiocytic type in the Rappaport classification, and 20 were large-cell immunoblastic type in the Working Formulation. Treatment regimens were not uniform, but included multiagent chemotherapy in 23 patients and radiation to the mediastinum in 20 patients. Twenty-three patients (92%) attained a complete remission (CR). Of these, 17 (74%) remain disease-free 13 to 65 months from diagnosis (median, 43 months). No CNS relapses have been observed. Mediastinal NLBL in the pediatric age group has distinctive clinicopathologic features that warrant special consideration in the design of treatment protocols.
Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Linfoma/tratamento farmacológico , Neoplasias do Mediastino/tratamento farmacológico , Adolescente , Criança , Pré-Escolar , Ciclofosfamida/administração & dosagem , Doxorrubicina/administração & dosagem , Feminino , Seguimentos , Humanos , Laparotomia , Linfoma/patologia , Linfoma/radioterapia , Masculino , Neoplasias do Mediastino/patologia , Neoplasias do Mediastino/radioterapia , Estadiamento de Neoplasias , Prednisona/administração & dosagem , Distribuição Aleatória , Vincristina/administração & dosagemRESUMO
We studied the organization of immunoglobulin (Ig) genes and the beta-chain gene of the T cell receptor (TCR) along with the clinical features, immunophenotypes, and karyotypes of 14 children with acute leukemia at diagnosis and relapse. The median time to relapse was 23 months. Eleven children had identical gene rearrangement patterns at diagnosis and relapse. All three patients whose blast cells showed variations in gene rearrangement patterns between diagnosis and relapase also demonstrated a change in the immunophenotype: one from cALLA+ to cALLA- B precursor cell ALL; one from T-ALL to AML; and one showed a marked increase in myeloid characteristics at relapse. Blast cells from these three patients at relapse showed the presence of chromosomal translocations involving 11q23; for two patients, this involved replacement of the original karyotype. We conclude that while most relapses are the result of reemergence of the original clone, new clones that differ in immunophenotype, karyotype, and gene rearrangement are occasionally present at relapse. Relapses may also occur in which the original clone has undergone major changes in gene expression and arrangement of the Ig heavy chain genes in the absence of karyotypic replacement.
Assuntos
Cromossomos Humanos Par 11 , Rearranjo Gênico do Linfócito T , Rearranjo Gênico da Cadeia beta dos Receptores de Antígenos dos Linfócitos T , Genes de Imunoglobulinas , Leucemia/genética , Translocação Genética , Doença Aguda , Adolescente , Criança , Pré-Escolar , Feminino , Humanos , Imunofenotipagem , Lactente , Cariotipagem , Leucemia/imunologia , Masculino , RecidivaRESUMO
Terms used to describe lung sounds in published case reports were tabulated, including qualifying adjectives. Seven journals were reviewed, and a total of 663 case reports were included. From the frequency of usage and similarity of qualifying adjectives it appears that "rales" and "crepitations" are equivalent terms. Many authors feel the need to qualify "rales": sixteen descriptive adjectives were encountered. Some authors distinguish between "rhonchus" and "wheeze," but the terms, for most, appear to mean the same thing. It is evident that current usage varies widely, even in the terminology of the basic categories of sounds.
Assuntos
Pneumopatias/diagnóstico , Sons Respiratórios/diagnóstico , Terminologia como Assunto , Auscultação , Humanos , Sons Respiratórios/classificação , Sons Respiratórios/fisiopatologiaRESUMO
Nine pediatric patients were treated with recombinant human tissue plasminogen activator (tPA) for severe hepatic veno-occlusive disease (VOD) which developed after bone marrow transplantation. Recombinant human tPA (5-10 mg/day x 2-4 days) and heparin were begun a median of 15 days (range, 11-32 days) post-transplant. A second course was given if the patient did not respond. The median total serum bilirubin and percent weight gain above baseline were 5.5 mg/dl (range, 1.3-26.1 mg/dl) and 22% (range, 7-44%) respectively at the start of tPA administration. Three patients had their heparin infusion interrupted or discontinued for bleeding symptoms, none of which were life-threatening. Five of the nine patients had complete resolution of their VOD. Another patient was salvaged with a partial maternal liver transplant. We conclude that the incidence and severity of bleeding complications with these doses of tPA and heparin do not preclude their use in pediatric patients. Further study in a larger group setting will be necessary to determine the optimal dosing regimen as well as treatment efficacy.
Assuntos
Transplante de Medula Óssea/efeitos adversos , Hepatopatia Veno-Oclusiva/terapia , Ativador de Plasminogênio Tecidual/uso terapêutico , Adolescente , Criança , Pré-Escolar , Feminino , Hemorragia/induzido quimicamente , Humanos , Lactente , Masculino , Proteínas Recombinantes/uso terapêutico , Terapia Trombolítica , Ativador de Plasminogênio Tecidual/efeitos adversosRESUMO
Eleven children underwent BMT for therapy-related MDS or leukemia, four from HLA-identical siblings and seven from unrelated donors. Ten of the 11 were conditioned with busulfan and cyclophosphamide as the majority had received prior irradiation to the chest and/or abdomen. All patients engrafted. Regimen-related toxicity was more common when compared to historical controls. Eight patients developed acute GVHD and four of eight who survived 100 days post transplant developed extensive chronic GVHD. Non-relapse related mortality occurred in three patients. Five patients developed recurrent malignancy: one died from recurrence of osteosarcoma, three died of recurrent leukemia or MDS and another developed two subsequent malignancies (duodenal carcinoma and anaplastic astrocytoma). Three survive disease-free at 14+, 22+ and 43+ months for a 2 year actuarial cancer-free survival of 24% (95% confidence interval = 5-53%). Although allogeneic BMT can be curative, regimen-related toxicity is frequent and recurrent malignancy remains the major obstacle.
Assuntos
Transplante de Medula Óssea , Leucemia/terapia , Síndromes Mielodisplásicas/terapia , Bussulfano/uso terapêutico , Criança , Pré-Escolar , Ciclofosfamida/uso terapêutico , Feminino , Sobrevivência de Enxerto , Humanos , Imunossupressores/uso terapêutico , Lactente , Leucemia/induzido quimicamente , Leucemia/patologia , Masculino , Síndromes Mielodisplásicas/induzido quimicamente , Síndromes Mielodisplásicas/patologia , Transplante Homólogo , Resultado do TratamentoRESUMO
The risk of Epstein-Barr virus lymphoproliferative disease (EBV-LPD) increases with the use of highly immunosuppressive therapies. Allogeneic BMT, especially supported by T-cell-depleted stem cell products, is a risk factor for EBV-LPD. Although the risk of EBV-LPD after autologous transplantation is low, case reports of this complication in the autologous setting exist. We report a higher incidence than previously described of EBV-LPD in children undergoing sequential high-dose chemotherapy supported with CD34 selected peripheral blood stem cells (CD34+ PBSC). The median time to LPD after tandem transplant was 3 months (range 1-5 months). Five patients out of 156 (3.5%) developed EBV-LPD while enrolled on two trials of tandem autologous SCT in high-risk pediatric malignancies. Both studies employed five cycles of induction therapy, followed by tandem autologous PBSC transplants. In all, 108 out of 156 patients received CD34+ PBSC; 48 received unselected PBSC. All patients contracting LPD were from the CD34 selected group. Treatment of EBV-LPD included rituximab in four out of five patients, i.v.Ig in two out of five patients, and gancyclovir in two out of five patients. EBV-LPD resolved in four out of five patients. We conclude that the combination of tandem SCT and CD34 selection may have increased immunosuppression in these patients to a point where there is an elevated risk of EBV-LPD.
Assuntos
Infecções por Vírus Epstein-Barr/epidemiologia , Transtornos Linfoproliferativos/virologia , Neuroblastoma/terapia , Transplante de Células-Tronco/métodos , Antígenos CD/sangue , Antígenos CD34/imunologia , Pré-Escolar , Feminino , Humanos , Incidência , Transtornos Linfoproliferativos/epidemiologia , Masculino , Transplante de Células-Tronco/efeitos adversos , Transplante Autólogo/efeitos adversosRESUMO
Six children with clinical and hematologic features of juvenile chronic myelogenous leukemia (JCML) underwent bone marrow transplantation (BMT) using T cell-depleted marrow from non-HLA-matched related or closely HLA-matched unrelated donors. Patient ages ranged from 1.2 to 5 years. Four patients received cytoreductive chemotherapy prior to BMT conditioning, and four had undergone pretransplant splenectomies. The donor-recipient matching included: four transplants disparate at one HLA locus (three from unrelated donors and one from a related donor), one transplant disparate at two HLA loci, and one transplant from a one haplotype-mismatched donor. All patients were MLC reactive with their donors. Graft-versus-host disease (GVHD) prophylaxis consisted of in vitro T cell depletion with a monoclonal antibody directed against CD3, and complement in conjunction with cyclosporin A begun on day -1. Conditioning included busulfan, cytosine arabinoside, cyclophosphamide, methyl-prednisolone, and hyperfractionated total body irradiation. All patients engrafted, with median time to neutrophils greater than 500 x 10(6)/l and platelets greater than 25 x 10(9)/l of 20 and 21 days, respectively. Acute GVHD was less than or equal to grade II in all patients. Two patients died of infection (Candida, CMV) at days 74, 157. One patient relapsed at day 177, and subsequently died on day 939. Three patients are alive and disease free at 180 +, 1610 + and 2400 + days from BMT. Although intensive chemotherapy may play a role in providing transient disease control in patients with JCML, allogeneic BMT is the only curative therapy.(ABSTRACT TRUNCATED AT 250 WORDS)
Assuntos
Transplante de Medula Óssea , Leucemia Mieloide Crônica Atípica BCR-ABL Negativa/terapia , Depleção Linfocítica , Pré-Escolar , Feminino , Doença Enxerto-Hospedeiro , Histocompatibilidade , Humanos , Lactente , Masculino , Indução de Remissão , Transplante HomólogoRESUMO
An 8-month-old girl with SCID presented with severe bronchiolitis. She received an HLA-identical sibling BMT without conditioning or GVHD prophylaxis. She deteriorated despite mechanical ventilation but had normal cardiac, hepatic and renal function. ECMO was instituted on day +3 and subsequent improvement was seen concurrently with emergence of CD4+ cells on day +11. She was taken off ECMO on day +18 and suffered a left-sided stroke evidenced by a dense left hemiplegia. She was extubated on day +25 and weaned from supplemental oxygen on day +36 and at day +100 has recovered strength in her extremities. This is the first successful use of ECMO as a bridge to engraftment in a BMT patient.
Assuntos
Transplante de Medula Óssea , Oxigenação por Membrana Extracorpórea , Imunodeficiência Combinada Severa/terapia , Feminino , Humanos , Recém-NascidoRESUMO
Increasing treatment intensity has improved outcomes for children with neuroblastoma. We performed a pilot study in the Children's Oncology Group to assess the feasibility and toxicity of a tandem myeloablative regimen without TBI supported by autologous CD34-selected peripheral blood stem cells. Forty-one patients with high-risk neuroblastoma were enrolled; eight patients did not receive any myeloablative consolidation procedure and seven received only one. Two patients out of 41 (4.9%) experienced transplant-related mortality. CD34 selection was discontinued after subjects were enrolled due to serious viral illness. From the time of study enrollment, the overall 3-year EFS and OS were 44.8 ± 9.6% and 59.2 ± 9.2% (N=41). These results demonstrate that tandem transplantation in the cooperative group setting is feasible and support a randomized comparison of single vs tandem myeloablative consolidation with PBSC support for high-risk neuroblastoma.
Assuntos
Neuroblastoma/mortalidade , Neuroblastoma/terapia , Transplante de Células-Tronco de Sangue Periférico , Condicionamento Pré-Transplante/métodos , Autoenxertos , Feminino , Humanos , Lactente , Recém-Nascido , Masculino , Projetos Piloto , Condicionamento Pré-Transplante/efeitos adversos , Viroses/etiologia , Viroses/mortalidadeRESUMO
Cytoreduction for hyperleukocytosis before the initiation of primary therapy may reduce morbidity and mortality from blast cell lysis in children with acute lymphoblastic leukemia (ALL) and from leukostasis in children with acute nonlymphoblastic leukemia (ANLL) or chronic myelogenous leukemia (CML). The clinical features of 35 children (23 with ALL, 5 with ANLL, and 7 with CML) who underwent cytoreduction before the institution of definitive therapy were studied. Twelve children had exchange transfusions and 23 underwent leukaphereses. The cytoreductive procedures were equally effective in removing peripheral leukocytes (median decrease, 60%) and produced no complications. Ten children required additional cytoreduction because of further leukocyte increase before chemotherapy became effective. Three children with ALL who had renal insufficiency and metabolic derangement prior to leukapheresis subsequently required additional therapeutic measures. Three children with respiratory symptoms attributable to leukostasis improved after cytoreduction, and there were no episodes of intracerebral hemorrhage. These observations demonstrate the safety and efficiency of exchange transfusion and leukapheresis, and provide support for the role of cytoreduction in the early management of cases of hyperleukostasis and leukemia in children.
Assuntos
Transfusão Total , Leucaférese , Leucemia/terapia , Leucocitose/terapia , Adolescente , Criança , Pré-Escolar , Feminino , Humanos , Leucemia/patologia , Leucemia Linfoide/terapia , Leucemia Mieloide/terapia , Leucocitose/patologia , MasculinoRESUMO
PURPOSE: The purpose of this study was to evaluate the effect of busulfan and cyclophosphamide (BUCY) as conditioning regimen for bone marrow transplantation (BMT) on growth of children following BMT. PATIENTS AND METHODS: Growth assessment was prospectively done in all 25 children who underwent BMT following BUCY conditioning from 1989 to 1994 at Children's Hospital of Philadelphia. The height and growth rates were expressed as standard deviation scores (SDS). The height SDS prior to BMT were compared with 1, 2, and 3 years post-BMT. The growth rate SDS 1 year and 2 years post-BMT were also compared. Pubertal children were excluded from the analysis of growth rate. Median age of patients was 7 years (range, 1.3-15 years). A total of 22/25 patients were transplanted for AML, and three patients had myelodysplastic syndrome. Equal numbers of patients had autologous and allogeneic transplants. Seven patients received corticosteroids for varying lengths of time. The pre-BMT height SDS (mean +/- SD) for the group was -0.4 +/- 1.3. The mean height SDS for 19 children at 1 year post-BMT was +/- 0.1 +/- 1.2 and for 10 children, 2 years post-BMT was -0.3 +/- 1.6. Seven children who were 3 years post-BMT had the mean height SDS of -0.2 +/- 1.5. There was no statistically significant difference between pre-BMT height SDS and 1 year post-BMT (p = 0.49) and 2 years post-BMT (p = 0.42). The mean growth rate at 1 year post-BMT was -0.1 +/- 2.7 and at 2 years post-BMT was -0.9 +/- 2.3. The difference was not statistically different (p = 0.15). Somatomedin-C (insulin growth factor 1, IGF-1) levels were normal in all 13 children tested at 1 year post-BMT. IGF binding protein (BP)-3 levels were done in 10 children at 1 year and were found to be normal in all. Thyroid function studies were done in all patients pre-BMT and 1 year post-BMT and were normal for all. Bone age assessment was appropriate for age in all 14 patients tested at 1 year post-BMT. CONCLUSIONS: There was no evidence of growth failure following BMT with BUCY conditioning in this group of patients.
Assuntos
Transplante de Medula Óssea/métodos , Bussulfano/efeitos adversos , Ciclofosfamida/efeitos adversos , Crescimento/efeitos dos fármacos , Adolescente , Desenvolvimento Ósseo/efeitos dos fármacos , Criança , Pré-Escolar , Feminino , Humanos , Lactente , Proteína 3 de Ligação a Fator de Crescimento Semelhante à Insulina/sangue , Fator de Crescimento Insulin-Like I/metabolismo , Masculino , Glândula Tireoide/fisiologiaRESUMO
The presentation of Hodgkin's disease as a primary bony lesion is unusual. Seventeen such cases have been reported, only three of which appear in the orthopedic literature. The prognosis for survival in these patients is poor, possibly because of difficulty in arriving at the correct early diagnosis. In two adolescent girls (ages 12 and 17) with primary Hodgkin's disease of bone, the diagnosis was made with uncertainty or delay. One of the patients died and the other has progressive disease, two and one-half years after the diagnosis was established. Earlier recognition may lead to better outcomes.
Assuntos
Neoplasias Ósseas , Doença de Hodgkin , Adolescente , Neoplasias Ósseas/diagnóstico , Neoplasias Ósseas/patologia , Criança , Diagnóstico Diferencial , Feminino , Doença de Hodgkin/diagnóstico , Doença de Hodgkin/patologia , Humanos , Tomografia Computadorizada por Raios XRESUMO
BACKGROUND: Despite improvements in the treatment of pediatric acute lymphoblastic leukemia, approximately one in five patients will develop recurrent disease. The majority of these patients do not survive. This limited institution study sought to improve event-free survival (EFS) by intensification of chemotherapy. PROCEDURE: Twenty-one patients with either an isolated marrow (n = 16) or a combined marrow and central nervous system relapse (n = 5) received treatment according to Children's Hospital of Philadelphia protocol CHP-540. Six patients had an initial remission of <36 months, and five patients had relapsed within 1 year of completion of phase III therapy. Induction and reinduction therapy consisted of idarubicin, vincristine, dexamethasone, asparaginase, and triple intrathecal chemotherapy. Consolidation and reconsolidation therapy employed high-dose cytarabine, etoposide, and asparaginase given in a sequential manner. Maintenance therapy included courses of high- or low-dose cytarabine followed by sequential etoposide and asparaginase pulse, moderate-dose methotrexate with delayed leukovorin rescue, and vincristine/dexamethasone pulses. Therapy continued for 2 years from the start of interim maintenance in the 16 patients who did not receive a bone marrow transplant (BMT). Two patients underwent an HLA-identical sibling BMT specified by protocol. Four received a nonprotocol-prescribed alternative donor BMT. RESULTS: The complete remission induction rate was 95%. With a median follow-up from date of relapse of 49 months in survivors, the actuarial EFS based on intent to treat is 75%. There were three toxic deaths in patients in CR and two deaths from relapse. CONCLUSIONS: This regimen is toxic but effective and deserves study in a larger setting.
Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Medula Óssea/efeitos dos fármacos , Recidiva Local de Neoplasia/tratamento farmacológico , Leucemia-Linfoma Linfoblástico de Células Precursoras/tratamento farmacológico , Adolescente , Antibióticos Antineoplásicos/administração & dosagem , Antimetabólitos Antineoplásicos/administração & dosagem , Antineoplásicos/administração & dosagem , Antineoplásicos Hormonais/administração & dosagem , Antineoplásicos Fitogênicos/administração & dosagem , Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Asparaginase/administração & dosagem , Transplante de Medula Óssea , Neoplasias do Sistema Nervoso Central/tratamento farmacológico , Criança , Pré-Escolar , Citarabina/administração & dosagem , Dexametasona/administração & dosagem , Intervalo Livre de Doença , Etoposídeo/administração & dosagem , Feminino , Seguimentos , Humanos , Idarubicina/administração & dosagem , Lactente , Injeções Espinhais , Masculino , Indução de Remissão , Vincristina/administração & dosagemRESUMO
Twenty-eight children with Down syndrome (DS) and acute lymphocytic leukemia (ALL) were compared to non-DS control leukemics matched by age, white blood cell (WBC) count, and treatment protocol to evaluate presenting manifestations, toxicity, and outcome. The DS children with ALL did not have unique clinical or biologic characteristics to distinguish their disease from that of non-DS patients. Eleven of the DS patients had successfully banded cytogenetic studies of their leukemic cells with the distribution of model chromosome number of 46 (n = 1), 47 (2), 48 (5), and greater than 50 (3). The abnormal leukemic line involved an isochromosome of the long arm of chromosome 9[i(9q)] in 3 cases. Multiagent chemotherapies induced complete remissions in 25 patients (85%), yet overall 5 year event-free survival was only 23 +/- 8% when compared to 64 +/- 9% for control children receiving similar therapies (P less than 0.01). A significant cause of treatment failure was late marrow recurrence in the DS children. Host toxicity was striking in these children. Severe congenital heart disease present in one-third contributed to 2 deaths during antileukemia therapy. Hyperglycemia secondary to diabetogenic agents and repeated bronchitis were common toxicities. Intolerance to the antifolate methotrexate with severe gastrointestinal and skin toxicities was universal. We conclude that the poor prognosis for the child with DS and ALL stems in part from their increased risk of complications and toxicity from intensive modern leukemia therapies, specifically antifolates.
Assuntos
Síndrome de Down/complicações , Leucemia-Linfoma Linfoblástico de Células Precursoras/complicações , Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Criança , Pré-Escolar , Terapia Combinada , Feminino , Humanos , Lactente , Cariotipagem , Masculino , Leucemia-Linfoma Linfoblástico de Células Precursoras/tratamento farmacológico , Leucemia-Linfoma Linfoblástico de Células Precursoras/terapia , Prognóstico , Indução de RemissãoRESUMO
Analyses of bone marrow blast cells collected at diagnosis and relapse from 68 children with acute lymphoblastic leukemia (ALL) demonstrated changes in the expression of cell markers in one-fourth of the patients. Loss of the common ALL antigen (CALLA) was a frequent change, occurring in 8 of the 51 cases initially classified as common or pre-B ALL. The HLA-DR antigen was either acquired or lost in 5 of the 68 cases, terminal deoxynucleotidyl transferase was lost in 6 of 25 cases, and reactivity of the T10 antigen with monoclonal antibodies was increased in 6 of 17 cases of non-T cell ALL. Conversion to acute nonlymphoblastic leukemia, so-called lineage switch, was noted in two cases of common ALL and one of pre-B ALL, coinciding with the loss of CALLA. Results of chromosomal analyses in cases with a loss of CALLA implicated several mechanisms in the observed phenotypic changes. In six cases, including each instance of lineage switch, the original karyotype had been replaced by an entirely different abnormal karyotype, suggesting clonal selection or induction of a second malignancy. In another case, the evidence suggested clonal evolution. Our findings demonstrate that sequential phenotypic and cytogenetic studies may yield valuable insights into the mechanisms of leukemic recurrence and may have implications for treatment selection.