Mauro Grossi

The use of intermediate dose methotrexate in increased risk childhood acute lymphoblastic leukemia a comparison of three versus six courses

Between January 1974 and November 1978, 41 consecutive increased risk (age <24 months or >120 months, or leukocyte count >30,000/mm3) patients with acute lymphoblastic leukemia (ALL) were entered on two consecutive treatment protocols which employed intermediate dose methotrexate (IDM). IDM was employed for central nervous system prophylaxis and systemic intensification. It was anticipated that the avoidance of prophylactic cranial irradiation would result in a lower incidence of long‐term central nervous system sequelae. Twenty‐two children and adolescents were entered on the first study (IDM × 3) which employed three courses of IDM (500 mg/m2) and six doses of intrathecal (IT) methotrexate (MTX). Nineteen children and adolescents were entered on the second study (IDM × 6) which employed six courses of IDM (3–500 mg/m2 and 3–1500 mg/m2), six doses of IT MTX and three additional doses of triple IT chemotherapy (MTX, cytosine arabinoside, and hydrocortisone or dexamethasone). The cumulative percentage of patients who remained in continuous complete remission was 30% for IDM × 3 and 57% for IDM × 6. This difference was statistically significant (P = 0.046). The site of first relapse was: bone marrow (BM), 7; CNS, 4—using IDM × 3; and BM, 2; CNS, 4; and BM + CNS, 1—using IDM × 6. The cumulative incidence of primary CNS relapse was 36.4% for IDM × 3 and 29.9% for IDM × 6. This difference was not statistically significant (P = 0.44). The use of more intensive therapy with IDM and triple IT chemotherapy did improve the duration of continuous, complete remission but did not decrease the incidence of primary CNS relapse in increased risk patients.

The use of different induction and maintenance chemotherapy regimens for the treatment of advanced yolk sac tumors.

Four children with yolk sac tumor were treated with an aggressive combination chemotherapy program. Three children had presacral primary tumors, one having pulmonary metastases, and one had a testicular primary tumor with pulmonary metastases. Three children were treated when they had measurable disease, and one had no measurable disease. The chemotherapy program consisted of a 6-wk induction period with vincristine (VCR), cis-diamminedichloroplatinum (DDP), and bleomycin. Maintenance therapy consisted of VCR, actinomycin D, and cyclophosphamide (cytoxan) every 3-4 wk as tolerated. Treatment was discontinued after 12 mo of complete remission. All three patients with evaluable disease had a partial response (PR) to induction therapy. Two underwent surgical exploration following induction therapy, one a laparotomy and the other a thoracotomy, and were found to have only scar tissue at the sites of presumed residual disease. The third child with measurable disease progressed to a clinical complete response (CR) during maintenance therapy. Two patients have had no evidence of disease (NED) for 42+ and 41+ mo since starting therapy (28+ and 27+ mo since completing treatment). Two patients are NED 11+ and 7+ mo since starting therapy and remain on treatment. We have encountered no significant renal or pulmonary toxicity, and there have been only two hospitalizations during maintenance therapy for fever and neutropenia. These preliminary results employing different induction and maintenance chemotherapy programs and planned second-look surgical intervention appear encouraging.

Clinical presentation of parvovirus B19 infection in children with aplastic crisis.

The records of 22 children with parvovirus B19-induced aplastic crisis were reviewed. The group consisted of 16 children with sickle cell hemoglobinopathies and 6 with hereditary spherocytosis. Children presented to the hospital 0.5 to 8 days (mean, 2.4 days) after the onset of symptoms. The children with sickle-cell disease presented earlier (mean, 1.4 days) than did children with hereditary spherocytosis (mean, 5 days; P = 0.02. Fever was the most common symptom, occurring in 73% of children. Rash did not occur in either group. Reticulocyte counts began to rise 1 week after onset of illness associated with a rise in parvovirus B19-specific IgG antibody. These data suggest that parvovirus B19 infection in children with sickle-cell hemoglobinopathies and heredity spherocytosis differs from infection in normal children.

Staphylococcus aureus bacteremia in children and adolescents with acute lymphoblastic leukemia.

37 episodes of Staphylococcus aureus bacteremia (SAB) in children and adolescents with acute lymphoblastic leukemia (ALL) were analyzed. 25 were associated with an identifiable source of infection: pneumonia (9), cellulitis (11), osteomyelitis (2), ear infection (2), urinary tract infection (1). The absolute neutrophil count was less than 1,000/mm3 at the onset of 29 episodes. 6 patients had a bacterial re-infection after the treatment for SAB was stopped. 5 patients had fungal infection discovered at autopsy. 7 patients died within 4 days of admission. Gram-negative superinfection occurred in 6 patients treated with multiple antibiotics whereas no patient among those treated with a single antibiotic developed superinfection. This was not a statistically different difference.

ACUTE OSTEOMYELITIS IN CHILDREN. REASSESSMENT OF ETIOLOGIC AGENTS AND THEIR CLINICAL CHARACTERISTICS

One hundred thirty-five children with acute osteomyelitis were identified by chart review during a 7-year period, January 1, 1980, through December 31, 1986. Bacteriologic causes were detected in 75 (55%) of the patients. Staphylococcus aureus, Haemophilus influenzae type b, and Pseudomonas aeruginosa were identified in 34 (25%), 16 (12%), and eight (6%) children, respectively. Staphylococcus aureus occurred in all age groups, H influenzae type b occurred only in children younger than 3 years and was the number one cause of disease in this group. Pseudomonas aeruginosa occurred exclusively in children older than 9 years. Children with H influenzae type b had clinical and laboratory findings that were almost indistinguishable from a matched group of children with osteomyelitis due to other known bacteria, although children with H influenzae type b tended to have more joint effusions (63% vs 27%), less lower extremity disease (22% vs 70%), and fewer positive cultures from bone or joint aspirates (41% vs 89%). Unlike most pediatric cases of osteomyelitis, the ones due to P aeruginosa did not represent the hematogenous route of infection; penetrating injury to the foot was present in every case. Children with P aeruginosa infections were older than 9 years (100%), predominantly male (88%), often afebrile (83%), and never bacteremic. These data provide guidelines for the initial work-up and management of osteomyelitis in children.