Experiencia del programa de trasplante de células progenitoras hematopoyéticas del Hospital de Pediatría Juan P. Garrahan / Experience of the hematopoietic stem-cell transplantation program at the Hospital Garrahan

El trasplante hematopoyético (TH) es la única o la mejor modalidad terapéutica para diversas enfermedades en Pediatría. Objetivos: Describir el programa de TH desarrollado en el Hospital de Pediatria Prof. Dr. Juan P. Garrahan y analizar prospectivamente la evolución de una cohorte de niños y adolescentes que recibieron en forma consecutiva TH en la unidad de TH. Resultados: 261 pacientes recibieron un TH alógenico y 5 pacientes un TH autólogo; 175 pacientes eran varones. La edad mediana fue de 8.2 años, (rango 0.1 -21). Las patologías más frecuentes fueron la Anemia aplástica adquirida severa (25 por ciento) y las leucemias agudas (46 por ciento). La tasa de mortalidad temprana fue 12.3 por ciento (IC95 por ciento: 8.7 -16.7 por ciento) y la tardía de 10.1 por ciento (IC95 por ciento= 6.8 - 14.3 por ciento). La probabilidad de sobrevida global fue de 62 por ciento (IC95 por ciento = 0.3971 - 0.8095) mediana (rango) de seguimiento de 45.6 meses (0.4-183.4). Las cataratas y los trastornos endocrinológicos fueron las complicaciones tardías más frecuentes. Los sobrevivientes presentaron una buena capacidad funcional y calidad de vida. Conclusiones. La selección de los pacientes y donantes, el desarrollo de la infraestructura de apoyo para la preparación de pacientes y donantes, y la capacitación del personal involucrado directa o indirectamente ha permitido alcanzar resultados de mortalidad relacionada al trasplante, sobrevida y calidad de vida comparables a los publicados por centros con vasta experiencia en pacientes pediátricos.

Nasopharyngeal carcinoma in childhood and adolescence: a single-institution experience with combined therapy.

BACKGROUND: A high cure rate may be attained for locally advanced, undifferentiated nasopharyngeal carcinoma (NPC) in children, provided that a combined modality of treatment is employed. Both local and systemic therapies are necessary. Results at a single pediatric institution were analyzed. METHODS: From November 1988 to December 1997, 16 consecutive patients were treated with NPC at the Hospital Garrahan in Buenos Aires, Argentina. The authors were able to evaluate 11 patients (9 boys and 2 girls); their median age was 12 (range, 8-14) years. Chemotherapy consisted of 3 courses, every 3 weeks, of 5-fluorouracil (500 mg/m(2)) plus bleomycin (15 mg/m(2)) daily for 4 days, with cisplatin (100 mg/m(2)) added the last day. External beam radiotherapy was delivered over a median of 52 (range, 45-63) days, to a median cumulative dose to the primary site of 55 (range, 50-61.2) grays (Gy). The median dose for the lower neck area was 45 (range, 45-55.8) Gy. All patients received radiotherapy to the primary site and to the initially involved lymphoid areas, with daily single doses of 1.8 Gy (5 of 7 days per week). RESULTS: The main symptoms at onset were cervical mass (100%), epistaxis (54%), cephalalgia (36%), and trismus (36%). All cases were Stage IV (American Joint Committee on Cancer and International Union Against Cancer TNM system). Complete response was achieved in 45% of patients after initial chemotherapy. With a median follow-up of 63 (range, 23-119) months, disease free survival (with standard error [SE]) and overall survival estimates were 61% (16%) and 91% (9%), respectively, at 75 months. Acute toxicity due to therapy was tolerable. Chronic sinusitis (73%), hypothyroidism (73%), and mild (64%) or moderate (9%) neck fibrosis were detected at follow-up. CONCLUSIONS: Although this series is small, the authors concluded that NPC patients have a good chance of survival in the setting described, in spite of locally advanced disease. Chemotherapy might be useful in preventing the development of systemic metastases.

Retinoblastoma with low risk for extraocular relapse.

OBJECTIVE: To define a subgroup of patients with retino-blastoma and low risk of extraocular relapse through histopathological and clinical variables. PATIENTS AND METHODS: Inclusion criteria consisted of stage I (intraocular disease), stage IIb1 (without concomitant choroid and/or scleral invasion), and nonenucleated patients (according to the Grabowski-Abramson classification). A total of 112 consecutive patients admitted to Hospital JP Garrahan from 1987 to 1997 were evaluable. Treatment included enucleation or local therapy and no chemotherapy. RESULTS: Forty-one patients had stage Ia (intraretinal), 8 stage Ib (prelaminar optic nerve invasion), 40 stage Ic (uveal invasion), and 12 stage IIb1 (postlaminar optic nerve invasion and cut end free of tumor). Eleven patients had neither eye enucleated. Median follow-up was 60 months. Only two events occurred: one patient had progressive disease in the contralateral globe and died of CNS metastasis and another had an orbital relapse that was successfully treated. Both had choroidal invasion. Five-year pEFS and pOS were 0.97 and 0.98, respectively. Neither length of the optic nerve stump, tumor size, anterior chamber invasion, degree of differentiation, nor degree of ocular coat invasion correlated with increased risk of metastasis. CONCLUSIONS: A subset of patients with retinoblastoma with low risk of relapse can be determined using histopathological evaluation of the invasion of ocular coats. Adjuvant chemotherapy is not warranted for patients with intraretinal extension and prelaminar optic nerve invasion. It is also probable that those patients with isolated choroidal invasion and those with postlaminar optic nerve extension with surgical margins clear of tumor do not need chemotherapy.

Successful related umbilical cord blood transplantation for graft failure following T cell-depleted non-identical bone marrow transplantation in a child with major histocompatibility complex class II deficiency.

Major histocompatibility complex (MHC) class II deficiency is a rare form of primary combined immunodeficiency that can only be corrected by stem cell transplantation. We report a 4(1/2)-year-old girl with MHC class II deficiency who underwent a related CBT due to graft failure following T cell-depleted non-identical BMT. The patient is alive and well 2 years after the second transplant. A sustained hematopoietic engraftment and a progressive immune recovery have been detected. We conclude that cord blood may be an effective source of hematopoietic stem cells for patients with immuno- deficiency disorders including diseases with a high rate of graft failure.

Randomized trial of CVPP for three versus six cycles in favorable-prognosis and CVPP versus AOPE plus radiotherapy in intermediate-prognosis untreated Hodgkin's disease.

PURPOSE: To evaluate in a randomized trial the impact of three versus six cycles of cyclophosphamide, vinblastine, procarbazine, and prednisone (CVPP) chemotherapy in favorable-prognosis and CVPP versus doxorubicin, vincristine, prednisone, and etoposide (AOPE) plus involved-field radiotherapy (RT) in intermediate-prognosis previously untreated Hodgkin's disease. PATIENTS AND METHODS: Of 256 patients evaluated, 80 with a favorable prognosis according to a prognostic index designed by the Grupo Argentina de Tratamiento de Leucemia Aguda (GATLA) were randomized to three versus six cycles of CVPP without RT and 176 with intermediate risk to CVPP versus AOPE, both for six cycles with RT between the third and fourth cycles of 30 Gy to the involved areas at diagnosis. CVPP consisted of intravenous (I.V.) cyclophosphamide and vinblastine on days 1 and 8, and oral procarbazine and prednisone on days 1 to 14, every 28 days. AOPE consisted of I.V. doxorubicin and vincristine on day 1, oral prednisone on days 1 to 5, and I.V. etoposide on days 1 and 3, every 28 days. RESULTS: Complete remission was obtained in 39 of 41 (95%) patients treated with three cycles of CVPP and 36 of 39 (92%) treated with six cycles in the favorable-risk group (difference not significant [NS]). In the intermediate-risk group, 89 of 92 (97%) treated with CVPP plus RT versus 75 of 84 (89%) treated with AOPE plus RT achieved a complete remission (P = .05). At 60 months, the event-free survival (EFS) and overall survival rates in the favorable-risk group were 80% and 91% for CVPP x 3 and 84% and 97% for CVPP x 6, respectively (P = NS). In the intermediate-risk group, 60-month EFS rate for CVPP plus RT was 85%, compared with 66% for AOPE plus RT (P = .009). The overall survival rate was 95% versus 87% respectively (P = .157). CONCLUSION: Three cycles of CVPP without RT are equally effective as six cycles in the favorable-risk group. However, in the intermediate-group, CVPP plus RT is superior to AOPE plus RT, with significantly fewer events before and after induction (P = .009), without a difference in overall survival.

Results of a stage-based protocol for the treatment of retinoblastoma.

PURPOSE: To describe the treatment of retinoblastoma at a single institution using a prospective protocol based on histopathologic staging. PATIENTS AND METHODS: We included 116 consecutive patients (101 eligible, 46 bilateral) from August 1987 to December 1993. Treatment was enucleation or conservative therapy for intraocular disease (stage I patients). Stage II patients (orbital or postlaminar invasion) received vincristine, cyclophosphamide, and doxorubicin for 57 weeks. Patients with orbital mass and extension beyond the cut end of the optic nerve also received orbital radiotherapy (45 Gy). The latter received intrathecal therapy. In those with CNS (stage III) or hematogenous metastasis (stage IV), cisplatin and etoposide were added along with cranial (in patients with a CNS mass and prophylactically in stage IV) or craniospinal (in patients with positive CSF) radiotherapy. RESULTS: The median follow-up time was 39 months (range, 12 to 84). The overall survival rate was 0.84. Survival rates according to stage were as follows: stage I probability of overall survival [pOS] = 0.97) (alive/total), 59 of 60; stage II (pOS = 0.85) including patients with scattered episcleral cells, three of three; orbital mass, one of one; postlaminar invasion up to and beyond the cut end of optic nerve, 10 of 11 and 11 of 14, respectively; of stage III (pOS = 0), zero of six; and stage IV (pOS = 0.50), three of six. Only those patients with preauricular adenopathy as the only metastatic site survived in the latter group. Acute toxicity was mild. CONCLUSION: Chemotherapy is not warranted to prevent systemic metastasis for intraocular disease. Patients with extraocular orbital disease and had a good outcome with this therapy. Patients with metastatic disease fared poorly, except for those with isolated malignant preauricular adenopathy.