Renato Mastrangelo

A new approach in the treatment of stage IV neuroblastoma using a combination of [131I]meta-iodobenzylguanidine (MIBG) and cisplatin

The outlook for disseminated neuroblastoma (NB) continues to be dismal. NB is a radiosensitive tumour. Owing to its high concentration in NB lesions, [131I]meta-iodobenzylguanidine [131I]MIBG has the potential for specifically delivering very large radiation doses to the malignant cells. Encouraging results have been reported with [131I]MIBG used alone in patients resistant to conventional therapy and at diagnosis. We report the first attempt to explore the integration of this new treatment modality with chemotherapy. Among the drugs effective in NB, cisplatin was chosen because of its high degree of activity against NB, its mild haematological toxicity and the known synergism between cisplatin and radiation. 4 patients, 3 with relapsed, heavily pre-treated, progressive stage IV NB, and 1 with stage IV NB at diagnosis, all with a good [131I]MIBG uptake, were investigated with combined therapy (CO-TH). Two complete remissions and one partial remission were observed in these patients 4-6 weeks following only a single course of both cisplatin and [131I]MIBG at standard dosage. The only toxicity was haematological, which was significant and relatively long-lasting, but was not associated with any serious infections or bleeding tendency. The general condition of these patients during the entire study period was excellent. The fourth patient, investigated at diagnosis with a modified less intensive treatment, obtained a partial remission with mild haematological toxicity. During the subsequent courses of intensive multidrug chemotherapy, this patient showed haematological toxicity comparable with that experienced by patients treated with an identical drug combination, but without previous treatment with CO-TH. The provisional conclusion of this ongoing study is that this new form of CO-TH appears most effective in obtaining a rapid and excellent response in heavily pretreated relapsed patients with progressive disease, and should be further investigated in earlier stages of the disease.

Constitutional trisomy 8 and myelodysplasia: Report of a case and review of the literature

A diagnosis of myelodysplastic syndrome was made in an 18-year-old patient with Warkany syndrome due to constitutional trisomy 8 mosaicism. The possible causal role of this particular chromosome constitution with respect to myelodysplasia and embryonal childhood tumors is discussed.

A melanotic neuroectodermal tumor of infancy arising from the anterior fontanel.

A case of local recurrence of melanotic neuroectodermal tumor of infancy (HINT), arising from the anterior fontanel in a 6-month-old female, is presented. The follow-up of 48 months after surgery confirms the benign nature of this tumor despite its local recurrence. Clinical and histopathologic characteristics of this rare tumor are discussed. A review of 12 cases of MNT involving the skull is given. It is emphasized that this entity should be kept in mind in the differential diagnosis of a mass in the craniofacial structures in infancy.

131I-metaiodobenzylguanidine in the treatment of neuroblastoma at diagnosis

Radioactive metaiodobenzylguanidine (131I-MIBG) is taken up specifically by neuroblastoma cells and appears to represent a new treatment modality in patients with advanced neuroblastoma. Taking into account the fact that all patients so far treated were heavily pretreated and resistant to chemotherapy, the results obtained appear encouraging. In order to explore further the potential role of this new drug in untreated patients, we treated with 131I-MIBG a child with stage III neuroblastoma at diagnosis. We observed the complete disappearance of a large abdominal tumor mass after a relatively low dosage of 131I-MIBG, with minimal hematologic toxicity. No further treatment was given and, at present, the patient is alive with no evidence of disease 18 months from diagnosis. This child represents, to our knowledge, the only case of neuroblastoma thus far treated at diagnosis and the excellent response obtained suggests the need for further investigations of this therapy in untreated patients.

Intermittent intrathecal methotrexate and fractional radiation (M-IMFRA) plus chemotherapy in childhood leukemia.

Preliminary results of our investigation concern 28 consecutive cases of children with acute lymphoblastic leukemia (ALL), treated between March 1974 and March 1978 at the Clinica Pediatrica of the Catholic University in Rome, with a slight modification of the ALL protocol II of the Childrens Hospital of Michigan (M-IMFRA). This protocol includes intermittent low dosage radiation of the cranio-spinal axis, combined with single intrathecal injections of methotrexate for the prophylaxis of central nervous system leukemia. Of the initial 28 children, one did not achieve a complete remission and one died of viral pneumonitis, 4 months after admission, in complete remission and had no hematologic toxicity at the time of this infection. The evaluation of remission duration is based on the remaining 26 children with a period of observation of up to 48 months. Only 2 children, who belonged to the low risk group, have so far relapsed, and relapse was confined to the bone marrow. Median survival without evidence of recurrence is 21 months. Or the 28 patients investigated, 17 are high risk children, as judged by the WBC above 20,000/mm3, mediastinal mass and age below 18 months or above 12 years. Only minimal toxicity has been observed in all cases. We have been encouraged to continue the regimen described here by recent observations regarding the abnormal computed tomography (ACT) scans in children with ALL following CNS prophylaxis of 2,400 rad to the skull. The high incidence of CAT scan abnormalities found is of interest and suggests a reappraisal of the current approaches to CNS prophylaxis.

Spontaneous leukocyte oscillation during blastic crisis of chronic myeloid leukemia

A spontaneous oscillation of the peripheral‐blood leukocyte count was observed in a 7‐year‐old girl with chronic granulocytic leukemia in blastic crisis. The time interval between nadir and nadir of approximately 2 months was similar to that found in other patients with CGL studied prospectively during the chronic phase of the disease. The spontaneous fluctuation of the ultimately prevailing blastic stem line is consistent with the view that the leukemic cells of the blastic crisis may not be fully autonomous. Implications regarding pathogenesis and therapy of the blastic crisis are discussed. Cancer 33:1610–1614, 1974.

A Specific Spontaneous Leucocyte Cycle in Chronic Myelogenous Leukemia

Cyclic leukocytosis has been previously described in patients with chronic myeloid leukemia (CML). The purpose of this report is to call attention to the possibility of a specific long-term cycle of approximately two months in CML, on the basis of the reported patients studied prospectively with no treatment and to describe an additional case with similar changes. Kinetic studies suggest that the leucocyte oscillation observed would reflect variation in cell production. Implications of the findings with regard to pathogenesis and therapy of the disease are discussed. A long-term cycle of the neutrophil count, showing a period of approximately two months, was also found in eight children with acute myelogenous leukemia (AML) in remission, analyzed retrospectively.

PROGNOSTIC FACTORS IN CHILDHOOD ACUTE LYMPHOBLASTIC LEUKEMIA

The real contribution to the treatment of childhood acute lymphoblastic leukemia (ALL) made by the identification of prognostic factors is undeniable. Biologic and clinical characteristics at diagnosis form the basis for assigning patients to risk groups. The therapeutic advantages of this include a reduction in the acute and late toxic effects of unnecessary therapy in patients with a good prognosis and a possible improvement, by using more intensive treatment, in the event-free survival of patients with a poor prognosis. Several prognostic factors including initial white blood cell (WBC) count, age, French-American-British morphologic classification, and immunophenotype associated with various prognostic impacts have been reported in different studies. More recently, cytogenetic features have been found to be useful for risk assignment since the presence of specific structural chromosome abnormalities in the leukemic cells, such as Ph + chromosome and t(4; 1 l), confers a very unfavorable prognosis, whereas hyperdiploidy with a modal number of 51 or greater is associated with an excellent outcome [ 11. Also, the number of glucocorticoid receptors per cell in leukemic lymphoblasts at diagnosis has prognostic implications, but this information is not easily available [2, 31. On the other hand, a short-term clinical trial with glucocorticoids appears to be simple and more useful, and the poor response to glucocorticoids, such as failure of blast clearance in the peripheral blood within a week, appears to be indicative of a highly adverse prognosis [4]. Treatment with more aggressive chemotherapy may influence the relevance of several prognostic factors, but some leukemias retain prognostic implications no matter what treatment is adopted. Leukocytosis at diagnosis, the first prognostic factor identified more than 25 years ago, still remains, in a multivariate statistical evaluation, the most important

Failure of Immunoglobulins to Prevent Neonatal Thrombocytopenia in Mothers with Immunothrombocytopenic Purpura

We report the case of a full-term (gestational age: 39 weeks) female newborn of a mother affected by immunothrombocytopenic purpura, treated with a high total dose (2 g/kg) of intravenous IgG, administered over a 3-day period starting 3 days before delivery. Infant platelet count at birth was 20,000/mm3 and she showed a great number of petechiae on the first day of life. After a random donor platelet transfusion and treatment with intravenous high-dose IgG (400 mg/kg for 5 days), platelet count began to increase. We conclude that exogenous IgG, even at high concentrations, apparently does not significantly cross the placenta, despite adequate maternal blood levels.