Purpose: We report a prospective study on brief IV antibiotic therapy in selected children with cancer experiencing fever and neutropenia (FN) after chemotherapy.Patients and methods: All children with FN (T degrees greater than or equal to 38 degrees C; ANC<0.5x10(9)/L) were hospitalized for treatment with broad spectrum IV antibiotics. They were divided into three groups: group A (no infection), group B (clinically documented infection). and group C (bacteremia), Children in group A (and some children in group B) were discharged before recovery of neutropenia, if afebrile and in good condition.Results: Eighty-eight consecutive episodes of FN occurred in 30 children. Children in group A (44 episodes; 50%) received IV antibiotics for a median of 3 days; on 25 occasions (57%), IV antibiotics were stopped before recovery of neutropenia. In children in group B (30 episodes; 34%), early discharge was allowed in eight cases of minor infections (27%); sire received oral antibiotics. Two children (group A) were rehospitalized for recurrent FN but recovered without complications.Conclusion: In chemotherapy-induced neutropenia, children hospitalized for fever but without documented infections and some children with minor infections can cautiously be discharged before evidence of bone marrow recovery if afebrile and in good general condition.

Purpose: Assessment of long-term survivors of childhood cancer for possible late effects of therapy is one of the most important issues in modern pediatric oncology.Patients and Methods: In a retrospective analysis of the files of 621 Swiss children and young adults surviving disease-free for 5+ years after the initial diagnosis, the Swiss pediatric Oncology Group (SPOG) could determine basic characteristics of this population: type of diagnosis, age at diagnosis and at evaluation, and frequency, type and severity of late effects. This study clearly demonstrated the necessity of evaluating long-term survivors systematically, in a standardized pre-established way. SPOG then assessed 30 representative long-term survivors in a pilot study using a standardized set of instruments.Results: Twenty (67%) of the 30 patients had late toxic effects of the cancer treatment. Nine (30%) had mild or insignificant problems, requiring follow-up but no current therapy. Eleven (37%) showed significant findings for somatic, cognitive or psychosocial functioning. Most often affected were the central nervous (15 patients), endocrine (9 patients) and musculoskeletal (5 patients) systems. Interestingly, formerly unknown late effects were detected by the pilot study in 13 (65%) of the 20 affected patients and required therapy (school or vocational counseling, psychomotor training, or hormonal replacement) in 6 of them. Conclusions: It can be assumed that a strategy of early detection and therapeutic intervention will be of great benefit for at least one-third of all long-term survivors of childhood cancer. Based on the observations from the retrospective and the pilot study, SPOG simplified its standard assessment, rendering it more tumor- and therapy-specific. The feasibility was enhanced and costs reduced, without jeopardizing the results. This revised set of tests is now used to assess, in a population-based cross-sectional study, all long-term survivors in Switzerland identified in the retrospective analysis.

Of 656 patients with ALL (all types) diagnosed in Switzerland during 4 consecutive 4-year periods (1976-1979, 1980-1983, 1984-1987, 1988-1991), 507 were officially registered on protocols ("study" patients) while 149 were not ("nonstudy" patients). The mean incidence of 3.8/100,000 children < 15 years/year is higher than reported for other Western countries. Evidence is presented suggesting that the 656 patients represent only approximately 90% of all children with ALL residing in Switzerland, indicating that the true incidence of ALL might even be higher. The fraction of "nonstudy" patients fell from 40% (1976-1979) to 15% (1984-1987). The rate of survival at 4 years of all patients with ALL ("study" and "nonstudy") increased by 17% during the three consecutive periods 1976-1979, 1980-1983, and 1984-1987. As expected, a higher increase (20%) was observed in "study" patients and a statistically nonsignificant lower one (10%) in "nonstudy" patients.

Based on the Swiss Pediatric Oncology Group (SPOG) cancer registry data during 1981-1991, a high average incidence of 8 new NHL per million children younger than 15 years per year was found. Of 162 children with NHL registered in 1976-1991, 120 were study patients, i.e., officially registered and treated according to SPOG or Pediatric Oncology Group (POG) protocols, while 42 were non-study patients, i.e., patients not officially enrolled on protocols. Overall, 91 of 120 (76%) study patients remained alive. Seventy-nine study patients were treated according to older SPOG protocols, and 53 (67%) of these survived, while 38 of 41 (93%) study patients treated according to newer POG protocols remained alive (P = 0.0068). Only 22 (52%) of the 42 non-study patients survived (P = 0.0001). There was no improvement if the survival of non-study patients before and since 1986 was compared. Population-based treatment results in Switzerland were similar to those in the United Kingdom. They provided an important base for the development of future treatment strategies.

Of 54 children with acute lymphoblastic leukemia (ALL) and first hematological recurrence observed between 1985 and 1989, 31 relapsed while still on treatment and 23 after cessation of therapy. Of the former, only one survived. Of the latter, 11 children survived after a minimum follow-up of 25 months. During the same period, a first isolated testicular relapse was observed in nine boys, of whom six survived, and an isolated CNS relapse in eight patients, of whom three survived. As a rule, survivors of a bone marrow or testicular relapse were doing well while those surviving a CNS relapse had considerable neuropsychological sequelae. These results, compared with those of two preceding studies, suggest that with intensification of front-line treatments, it becomes more difficult to rescue children who relapse, particularily those with a bone marrow relapse while on therapy. (C) 1994 Wiley-Liss, Inc.

Right atrial thrombosis (RAT) is infrequently diagnosed in children with cancer. Once RAT is documented, medical fibrinolysis or surgical thrombectomy is recommended. A RAT was documented in a child with lymphoma and was successfully lysed with recombinant tissue-type plasminogen activator. The case is presented and therapeutic options reviewed.

Three patients with CML who relapsed after transplantation with T-depleted BM from their HLA-identical siblings were treated with transfusions of donor peripheral blood mononuclear cells, in combination with (short) IFN alpha2 therapy. CML was successfully controlled as shown by the complete disappearance of Philadelphia-positive metaphases within 90 days of treatment. This treatment appears to be very effective as neither bcr-abl transcripts nor markers specific for hematological cells of recipient origin could be detected by very sensitive PCR techniques. Two patients treated in chronic phase are without evidence of disease 300 and 360 days after treatment. The third patient, treated in accelerated phase, died with BM aplasia, 39 days following PBMC infusions. Failure to detect residual donor-derived granulocytes, as was the case in this patient prior to initiating adoptive immunotherapy, may indicate toss of donor-derived BM activity. This may help predict and possibly prevent the occurrence of life-threatening aplasia after successful clearance of malignant hematopoiesis.

We have studied the value of additional immune suppression in BMT conditioning regimens in 45 patients with leukemia and 4 with myelodysplastic syndrome allografted between 1984 and 1991. A dose of 6 Gy total lymphoid irradiation (TLI) was delivered to 12 of 24 and 15 of 25 patients conditioned with 10 Gy and 12 Gy total body irradiation (TBI), respectively. Thirteen patients also received methylprednisolone (MP) before BMT to enhance immunosuppression. Differences in immunosuppression between the TBI with or without TLI or MP regimens and the influence of different levels of graft T cell depletion were measured in terms of transplant rejection, and complete versus mixed chimerism. The treatment-related complications were evaluated in terms of GVHD and incidence of pneumonitis. The overall transplant rejection rate was 6% (3 of 49). Complete chimerism was not significantly modified by increasing the TBI dose or by additional TLI (p > 0.10) but was more often seen in patients receiving MP given as pre-transplant immunosuppressor booster (p = 0.01). The incidence of GVHD was only influenced by the level of T cell depletion (p = 0.003). All 49 patients received a TBI lung dose in the range 9.5-10 Gy. A crude pneumonitis range of 19% (9 of 47 evaluable patients) was found. Neither the addition of TLI, MP nor the T cell depletion influenced the lung toxicity rate (p > 0.10) but pneumonitis was more frequent in patients with GVHD (p = 0.005).

A case of severe cardiac failure due to iron overload in a patient with beta-thalassemia major is reported. The patient was successfully treated with high-dose ambulatory intravenous deferoxamine (desferrioxamine). This type of chelation appears to be a valuable alternative to subcutaneous deferoxamine administration in the presence of severe iron overload.

Bone marrow transplantation from the unrelated volunteer donor is today a realistic possibility for patients lacking an HLA-identical family donor. In 1988, the Swiss Unrelated Bone Marrow Donor Registry was founded to coordinate such bone marrow transplants and create the Swiss volunteer donor registry. Thus for a search has been initiated for 71 patients and 16 transplants have been performed. Donor and recipient were HLA-A-, -B-identical by serology and HLA-Dr-identical by DNA-oligotyping. 10 of the 16 patients are alive without signs of basic disease 2 weeks to 2 years and 4 months after the transplant. These results illustrate that unrelated donor transplantation, using careful selection criteria, is a realistic new therapeutic modality.

Bone marrow transplantation from the unrelated volunteer donor is today a realistic possibility for patients lacking an HLA-identical family donor. In 1988, the Swiss Unrelated Bone Marrow Donor Registry was founded to coordinate such bone marrow transplants and create the Swiss volunteer donor registry. Thus for a search has been initiated for 71 patients and 16 transplants have been performed. Donor and recipient were HLA-A-, -B- identical by serology and HLA-Dr-identical by DNA-oligotyping. 10 of the 16 patients are alive without signs of basic disease 2 weeks to 2 years and 4 months after the transplant. These results illustrate that unrelated donor transplantation, using careful selection criteria, is a realistic new therapeutic modality.

Recombinant human erythropoietin (rHuEPO) was administered subcutaneously three times a week to 18 infants with the anaemia of prematurity at doses of 75, 150, 300, or 600 units/kg per week for 4 weeks, starting at 3-4 weeks of postnatal age. A significant and dose-dependent increase in reticulocyte count was observed from a mean baseline value of 71 x 10(9)/l to 200 x 10(9)/l after 3 weeks of therapy, compared with a change from 69 to 97 x 10(9)/l in 66 historical controls. The haematocrit value remained unchanged during rHuEPO treatment, whereas it steadily declined until 9 weeks of postnatal age in the controls. These effects were accompanied by a marked reduction in serum iron concentration and transferrin saturation in patients receiving standard-dose iron supplements, but not in those given larger doses. Only 3 of 18 patients required a red blood cell transfusion. These infants were among the most anaemic at entry into the study and 2 of them were unable to complete rHuEPO therapy, while the third developed iron deficiency anaemia. These data indicate that rHuEPO with appropriate iron supplementation may accelerate the recovery from anaemia of prematurity. Larger scale placebo-controlled studies are now needed to confirm these findings and verify their impact on transfusion requirements of premature infants.

From June 1982 until December 1989, 93 permanent central venous catheters [59 external catheters (ECs) and 34 implanted catheters (ICs)] were placed in 69 patients. The median age of these patients at placement was 5.6 years for ECs and 8.8 years for ICs (P<0.05). Follow-up evaluation was possible on 86 catheters (58 ECs and 28 ICs). The median time of insertion was 236 days and 316 days for ECs and ICs, respectively (P<0.05). The median number of open days was 58 for ECs and 66 for ICs (not significant). 17 catheters (6 ECs and 11 ICs) were transiently obstructed (P<0.005). 30 episodes of bacteraemia were documented in 20 patients. The incidence of catheter sepsis and bacteraemia of unknown source was one in 278 and 283 open days for ECs and ICs, respectively (not significant). In this retrospective study, ECs appeared to be as safe as ICs when infection was correlated with use of the catheter, but this finding should be confirmed in a randomised design.

Human granulocyte colony-stimulating factor (hG-CSF) is a glycoprotein which, in conjunction with other colony-stimulating factors, controls myelopoiesis [1–3]. Recombinant (r) hG-CSF and natural hG-CSF have similar effects in vitro. In man, rhG-CSF causes marked increases in peripheral blood neutrophil counts within 4 h. Elevations of neutrophil counts are dose dependent at recommended doses. Neutrophils produced in response to rhG-CSF show normal function [4]. Following termination of rhG-CSF therapy, circulating neutrophil counts decrease by 50% within 2 days and to baseline levels within 1 week [5, 6].

Anemia of prematurity (AP) is a common complication in infants <32 weeks of gestation. It is more marked (Hb ⩽90 g/L in 50% of patients) and occurs earlier (4–8 weeks of life) than the physiologic anemia of term newborns [1, 2]. Although clearly of a multifactorial etiology, AP partly results from an abnormal or immature erythropoietin (EPO)-mediated regulation of erythropoiesis [3–6]. EPO is a glycoprotein normally secreted by peritubular renal cells in response to hypoxemia [7]. Its action is principally directed onto the marrow erythroid progenitor cells (CFU-E), the proliferation and maturation of which are entirely dependent on the presence of this hormone. While older children and adults promptly respond to even a mild degree of tissue hypoxia by increasing their endogenous production of EPO, premature infants are not capable of producing an adequate response until their red cell mass reaches critical values [3, 4, 6]. Thus, AP may have important clinical repercussions resulting from decreased O2 availability, such as tachycardia, tachypnea, poor weight gain, and respiratory pauses [8, 9]. The most symptomatic of these premature infants are commonly transfused with packed red cells, despite current restrictive use of blood products. Therefore, unlike the anemia of infants born at term, AP cannot be considered as a simple physiologic, adaptive phenomenon.