Diet in children with phenylketonuria and risk of cardiovascular disease: A narrative overview.

AIMS: The aim of this paper is to review the possible relationship of restricted phenylalanine (Phe) diet, a diet primarily comprising low-protein foods and Phe-free protein substitutes, with major cardiovascular risk factors (overweight/obesity, blood lipid profile, plasma levels of homocysteine, adiponectin and free asymmetric dimethylarginine (ADMA), oxidative stress and blood pressure) in PKU children. DATA SYNTHESIS: In PKU children compliant with diet, blood total cholesterol, low-density lipoprotein cholesterol (LDL-C), plasma ADMA levels and diastolic pressure were reported to be lower and plasma adiponectin levels to be higher compared to healthy controls. No difference was observed in overweight prevalence and in high-density lipoprotein cholesterol (HDL-C) levels. Inconsistent results were found for plasma homocysteine levels and antioxidant status. CONCLUSIONS: PKU children compliant with diet seem to display non-different cardiovascular risks compared with the healthy population. Well-designed longitudinal studies are required to clarify the potential underlying mechanisms associated with PKU and cardiovascular risk factors.

153Samarium-EDTMP administration followed by hematopoietic stem cell support for bone metastases in osteosarcoma patients.

BACKGROUND: Bone metastatic patients with osteosarcoma have a very poor prognosis. Targeted radiation therapy has been pursued as a valid alternative. The primary end point of this study was progression-free survival (PFS) at 4 months. PATIENTS AND METHODS: Twenty-two osteosarcoma patients were treated with Samarium-153 ethylenediaminetetramethylene phosphonic acid (153Sm-EDTMP) at various dosages. Administered activities ranged from 150 (3 mCi/kg) to 1140 MBq/kg (30 mCi/kg). Autologous hematopoietic stem cell infusion was carried out on day 14 after the (153)Sm-EDTMP infusion. RESULTS: The median PFS was 61 days (18-436 days) and the median overall survival (OS) was 189 days (31-1175 days). PFS and OS for the entire patient population were 32% [95% confidence interval (CI) 16-50] and 76% (95% CI 52-89) at 4 months, respectively. No statistical differences emerged according to 153Sm-EDTMP administered or 24-h retained activity. One-month pain palliation was only observed in a minority of subjects and in none at 4 months. CONCLUSIONS: Based on our series, the PFS is dramatically short even when higher activity of (153)Sm-EDTMP is administered. This would mean that, even at high level, 153Sm-EDTMP is itself ineffective against relapsed osteosarcoma or the residual activity is too low to be active on these particular subsets of patients.

Intrathecal methotrexate affects cognitive function in children with medulloblastoma.

BACKGROUND: Cognitive impairment occurs after malignant brain tumor treatment in children, following brain radiotherapy and systemic and intrathecal chemotherapy. OBJECTIVES: 1) To compare two groups of children who underwent surgery for cerebellar medulloblastoma with their cousins and siblings, assessing intelligence, executive function, attention, visual perception, and short-term memory. Both groups were treated with the same combined radiotherapy-chemotherapy, but differed in that only one group received intrathecal methotrexate (MTX+). 2) To relate these measures to MRI findings (leukomalacia). RESULTS: The two groups performed worse than their control subjects in all tests. The MTX+ group younger than 10 years performed significantly worse in all tests, particularly executive ones. The group older than 10 years performed significantly worse only in short-term memory. Younger patients without MTX performed significantly worse than controls only in some neuropsychological measures; there were no differences between older patients and control subjects. Only in the MTX+ group was there a direct correlation between extent of leukomalacia and performance in some tests. CONCLUSIONS: The administration of intrathecal methotrexate to children with medulloblastoma worsens the cognitive deficits induced by chemotherapy and radiotherapy. The use of intrathecal methotrexate in the treatment of medulloblastoma and other malignancies should be reassessed.

Serum and cerebrospinal fluid human chorionic gonadotropin (hCG) and alpha-fetoprotein (AFP) in intracranial germ cell tumors.

We report a retrospective study on serum and cerebrospinal fluid (CSF) alpha-fetoprotein (AFP) and beta-human chorionic gonadotropin (betahCG) determination in a series of 30 patients bearing intracranial germ cell tumors. At diagnosis five patients had high serum and CSF AFP levels. No patient had positive serum AFP and negative CSF AFP or vice versa. Twelve of 30 patients had serum betahCG levels above 5 mlU/mL, eight had high betahCG only in CSF, and ten were completely negative. During treatment and follow-up both markers were accurate indicators of the response to therapy, decreasing rapidly and often becoming normal already after the first phase of treatment. We conclude that these two markers, and mostly betahCG, may be useful in the diagnosis and monitoring of the response to therapy of patients with intracranial germ cell tumors.

Phase II trial of temozolomide in children with recurrent high-grade glioma.

PURPOSE: The objective of the study was to evaluate the efficacy and toxicity of Temozolomide (TMZ) administered for 5 consecutive days in three daily dosing in children with recurrent or refractory high-grade glioma. PATIENTS AND METHODS: Twenty-four patients with a median age of 10.5 years were enrolled onto this open-label, multicenter, phase II study. The patients were previously treated with surgical resection (17 of 24), radiotherapy (19 of 24) and chemotherapy (18 of 24). Therapy was administered orally three times a day for 5 consecutive days at the dose of 200 mg/m(2)/dx5 for chemotherapy naive patients. In patients heavily pretreated with chemotherapy the starting dose was of 150 mg/m(2)/dx5. RESULTS: A total of 95 cycles were administered. The median progression free-survival (PFS) was 3 months for the entire group while disease stabilization was obtained in 7 patients (29.1%), all with supratentorial tumors. No CR or PR was observed. TMZ treatment showed a limited toxicity. Thrombocytopenia was the most common hematological adverse effect. Our data suggest a marginal activity of TMZ in children with recurrent high-grade glioma.

Stage 4 neuroblastoma: sequential hemi-body irradiation or high-dose chemotherapy plus autologous haemopoietic stem cell transplantation to consolidate primary treatment.

The aim of the present study was to evaluate the effectiveness of two consecutive nonrandomised treatment programs applied between 1989 and 1999 at the Istituto Nazionale Tumori of Milan in an unselected cohort of 59 children over the age of one with stage 4 neuroblastoma. Both treatment programs consisted of two phases, the induction of the remission phase and the consolidation phase. The induction of the remission phase consisted of intensive chemotherapy, and remained the same throughout the study period. The consolidation phase consisted of sequential hemi-body irradiation (HBI) (10 Gy per session, 6 weeks apart) in the first period (1988-June 1994) and sequential high-dose cyclophosphamide, etoposide, mitoxantrone+L-PAM and autologous haemopoietic stem cell transplantation in the second (July 1994-1999). Intention-to-treat analysis revealed a significantly better outcome for patients treated with the second program, the 5-year event-free survival probability being 0.12 for program 1 and 0.31 for program 2 (P=0.03). This finding led us to conclude that sequential HBI is useless as consolidation treatment. The high-dose chemotherapy adopted in the second program enabled a proportion of patients to obtain long-term survival but, since the clinical results remain unsatisfactory, new treatment strategies are warranted.

Juvenile classic Kaposi's sarcoma: a report of two cases, one with family history.

Two cases of juvenile classic Kaposi's sarcoma (KS), one with family history, are described, and the natural history of KS is briefly reviewed. Case 1a was a child whose disease ran an aggressive course and did not respond to therapy. Case 1b was the mother of the child: She had a relapsed localized form that was treated by surgery and chemotherapy, and she has been disease free since 1990. The second juvenile case was a 4-year-old boy with a localized form that relapsed but was successfully treated by surgery, chemotherapy, and radiation therapy. He has been free of disease since 1986. Family history in juvenile KS has not previously been reported unrelated to acquired immunodeficiency syndrome in a Western country.

Tropisetron (ICS 205-930) in pediatric oncology: first results in patients refractory to antiemetic metoclopramide-based treatments.

PURPOSE: We evaluated the antiemetic efficacy of tropisetron, a 5-HT3 receptor antagonist, during its compassionate use in children with malignant disease who during previous chemotherapy cycles experienced emesis refractory to metoclopramide-based treatments. PATIENTS AND METHODS: Tropisetron was given to 15 children (eight boys and seven girls 18 months to 18 years of age) with miscellaneous neoplasms. Generally 5 mg/day of tropisetron was administered i.v. the first day of cisplatin-based chemotherapy and i.v. or orally each subsequent day of chemotherapy. The dose of tropisetron was reduced to 2 mg/day in children < 2 years of age and weighing < 20 kg. RESULTS: Vomiting was well controlled (no more than two episodes per day) on 118 of the 184 days of treatment with tropisetron (64%). No clinically important variations were observed in blood pressure, heart rate, body temperature, or electrocardiographic findings attributable to tropisetron. Transient, mild to moderate side effects (headache, constipation, abdominal pain, diarrhea) occurred in five patients on 11 of the 184 days of tropisetron treatment (6%). CONCLUSION: The results obtained during compassionate use of tropisetron confirm that it is a valid, safe, and manageable antiemetic for the treatment of pediatric patients.

Case report: Pseudomonas aeruginosa-related intervertebral discitis in a young boy with medulloblastoma.

We report a case of a 15-year-old boy with desmoplastic medulloblastoma of the posterior fossa (T3M3, according to Chang classification) incompletely resected, with leptomeningeal and nodular spread in the posterior fossa and in the cervical and thoracic tracts of the spine, treated with sequential high dose iv chemotherapy and with hyperfractionated cranio-spinal radiotherapy. While on maintenance chemotherapy, the boy developed fever and septic status caused by Pseudomonas aeruginosa, and 1 week later also low back pain. Magnetic resonance imaging (MRI) demonstrated abnormal signal in the fourth ventricle and in the dorso-lumbar tract suggesting medulloblastoma recurrence, so he started with a chemotherapy program. Due to a worsening of back pain, a second MRI of the spine was performed that showed a spondilodiscitis of T11-T12 and L1-L2 discs. The histological and cultural examination of a fine-needle biopsy of the L1-L2 disc revealed the presence of P. aeruginosa. So patient was treated with intensive antibiotic therapy with resolution of the infection. Spondilodiscitis is a rare complication in neoplastic patients, maybe due to either immunodeficient status or invasive procedures such as lumbar puncture. This case demonstrates that MRI is a useful method for differentiating between infection and malignancy in the spine, but sometimes it may be difficult to distinguish metastatic tumor from a lesion due to spondilodiscitis. In this case surgicopathological assessment is crucial and mandatory.

Phenotypic and functional analysis of lymphocytes infiltrating paediatric tumours, with a characterization of the tumour phenotype.

Tumour-infiltrating lymphocytes (TIL) of paediatric tumours obtained from 37 lesions of different histotype (12 osteosarcomas, 5 Wilms' tumours, 7 soft-tissue sarcomas, 5 neuroblastomas and 8 miscellaneous) were studied to establish their potential for therapy. Fresh isolated TIL were cultured for the first 2 weeks with low doses of interleukin-2 (IL-2) (20 Cetus U/ml) to select for "tumour-specific" lymphocytes potentially present in the neoplastic lesion, followed by culture with high doses of IL-2 (1000 Cetus U/ml) to achieve TIL expansion. TIL were grown with more than 10-fold expansion in only 9 cases (mean expansion: 58-fold, range 13.5-346). In 17 cases no viable cells were obtained. After 30 days of culture with IL-2 the proliferative ability of TIL declined sharply in the majority of cases and TIL became refractory to any further stimulus, including addition of IL-4, tumour necrosis factor alpha (TNF alpha) or interferon gamma, and activation with OKT3 in solid phase. In 20 out of 37 cases TIL were available for phenotypic and functional analysis. TIL after long-term culture were predominantly CD3+ but 2 cases of osteosarcoma showed a predominance of CD3+TcR gamma/delta cells. The CD4/CD8 ratio was more than 1 in 10 cases, without correlation with tumour histology, site of lesion or TIL growth. The number of CD16+ and CD25+ lymphocytes decreased progressively during culture, the latter concomitantly with a reduction of TIL growth rate. The lytic pattern of TIL against allogenic and autologous tumour (Auto-Tu) cells was variable, but specific lysis of Auto-Tu was seen in only one case (Wilms' tumour) after culture with TNF alpha and irradiated Auto-Tu cells. The immunohistochemical analysis of tumour lesions revealed a limited lymphocyte infiltrate, a low expression of histocompatibility leukocyte antigens (HLA) class I and of the adhesion molecules ICAM1, LFA3, and a significant production of transforming growth factor beta (TGF beta). These data indicate that TIL obtained from paediatric patients are difficult to expand at levels required for immunotherapy and lack a significant number of tumour-specific T lymphocytes. A low expression of immunomodulatory molecules on tumour cells or the production of suppressive factors may prevent activation and expansion of TIL in paediatric tumours.

Gallium scan in adolescents and children with Hodgkin's disease (HD). Treatment response assessment and prognostic value.

AIM: The aim of the present paper is to describe the accuracy of gallium ((67)Ga) scintigraphy in adolescents and children with Hodgkin's disease (HD). We have studied the diagnostic value of this nuclear imaging technique at disease presentation (staging) and its prognostic value based on changes in (67)Ga uptake observed after treatment (response assessment). METHODS: From April 1985 to July 1999 74 consecutive untreated patients with a median age of 13 y underwent (67)Ga scans 48-72 h after injection of 37-111 MBq of (67)Ga-citrate. Planar whole-body scintigraphy was performed, supplemented with single photon emission tomography (SPET) of the mediastinum from 1996 onwards. Three patients did not undergo further scintigraphic examination because they were treated with radical surgery. After the 1st examination 71 of the 74 patients were monitored by 1-3 (67)Ga scans during the course of their disease. All of them had at least one (67)Ga scintigraphy at the end of the induction phase of chemotherapy, before any other therapeutic regimens were planned. RESULTS: At disease presentation (67)Ga scintigraphy was positive in all patients, detecting 285 of 335 (85.0%) lymph nodal sites of disease. The best sensitivity was observed in the mediastinum (100%; 63/63) and the laterocervical supraclavicular region (85.6%; 125/146); it was lower for axillary (72.7%; 16/22) and retroperitoneal (68.7%; 11/16) lymph node masses. In detecting visceral involvement the sensitivity of (67)Ga scintigraphy was 66.6% (8/12) for lung and 80% (4/5) for bone involvement. Among 71 patients in follow-up, 2 showed rapid progression of disease during induction therapy while 69 patients were monitored for a long period. The response to therapy has been classified according to the changes observed on nuclear medicine or radiological images as complete response (CR) or partial response (PR). On the basis of (67)Ga scans 55 patients (72.4%) were considered as having a CR, while with radiological modalities (chest X-ray, CT, MRI) CR was observed in only 29 patients (40.8%). PR or progression was found with (67)Ga scintigraphy in 16 patients (22.5%) and with radiological modalities in 42 patients (59.1%). (67)Ga scan was concordant with clinical outcome in 97% (28/29). The diagnostic effectiveness of this imaging technique has been analysed by comparing the scintigraphic or radiological changes at the 1st scintigraphic/radiological follow-up examination after induction therapy with the clinical outcome. In this population the relapse rate was 50% (8/16) in the group that did not achieve a CR according to post-treatment (67)Ga scintigraphy, while it was only 10.9% (6/55) in the group that achieved a CR on the basis of scintigraphy findings. The overall survival (OS) and disease-free survival (DFS) were calculated by means of Kaplan-Meier cumulative survival plotting. When the 2 groups of patients with complete (CR) or incomplete normalisation (PR or progression) of (67)Ga scintigraphy were compared, both OS and DFS were found to be statistically different (p=0.0001 and p=0.0004, respectively). By contrast, no statistical difference was found when the radiological findings were considered as the criterion for assessment of tumour response. On the basis of X-ray results the relapse rate was 13.7% in patients with negative post-therapy findings and 23.8% in patients with positive radiological imaging. CONCLUSION: Our data demonstrate the high value of (67)Ga scintigraphy in HD staging in paediatric patients. In addition, evaluation of the (67)Ga uptake is very useful as a prognostic parameter; changes in (67)Ga uptake after therapy indicate a favourable prognosis, whereas children still positive on post-treatment (67)Ga scintigrams should be given more aggressive treatment.

Treatment of childhood post-irradiation sarcoma of bone in cancer survivors.

PATIENTS AND METHODS: This is a retrospective review of five children with post-irradiation bone sarcoma (PIS). Age at PIS onset ranged between 10 and 17 years (median 11). They were treated with a chemotherapy regimen, similar to that in use for primary osteogenic sarcoma, consisting of vincristine and high-dose methotrexate alternated with cisplatinum and ifosfamide, given for 12 months. RESULTS: In all children chemotherapy induced a complete clinical remission. Four of them were alive in continuous complete remission at 1, 2, 4, and 12 years from the diagnosis of bone sarcoma. One girl recurred 3 years from PIS diagnosis and was salvaged by repeating the same chemotherapy program: she remained alive in second complete remission 8 years from relapse. CONCLUSIONS: In spite of an intensive treatment previously given for the primary tumor, this drug schedule proved to be feasible and short-term side effects were manageable. Chemotherapy alone, using an intensive regimen effective for primary osteogenic sarcoma, may be an adequate therapy for childhood post-irradiation sarcoma.

Management of medulloblastoma and ependymoma in infants: a single-institution long-term retrospective report.

To reduce the sequelae from CNS irradiation (RT), 16 children younger than 3 years with medulloblastoma-PNET (13 cases) and ependymoma (3 cases) were treated between 1987-1993 according to different postsurgical chemotherapy (CT) programs. None of these patients presented with metastases. Eleven patients were rendered disease-free by surgery, while 5 had residual tumor. Adjuvant therapy depended on patients' age, postsurgical status and parents' consent to radiotherapy (RT). Nine of the 16 infants remained alive in continuous complete remission from the first neoplasm (median follow-up 7 years). Three of them had been treated with CT alone and 6 with combined CT + RT (posterior fossa 4, whole CNS 2). Seven patients relapsed a median of 13 months after diagnosis, and all 7 of them died of their disease. Despite the omission of RT in 6 of the 16 patients and administration of only focal RT in 8 of the 16, the outcome of this series was satisfactory. Local failure (in 5/7 patients) was the major problem, despite the high dose of RT used in 2 of these 5. In 4 of 6 evaluable children school performance was satisfactory. One child in whom the entire CNS was irradiated developed glioblastoma multiforme 120 months after the first diagnosis of medulloblastoma.

Childhood liposarcoma: a single-institutional twenty-year experience.

A retrospective observational study was performed on a series of 12 consecutive pediatric patients treated over a 20-year period at the Istituto Nazionale Tumori, Milano. Conservative surgery was the treatment of choice in all patients; radical excision was obtained at diagnosis in 9 cases and after primary chemotherapy in 1 case. Five patients were subjected to surgery alone, and one to postoperative radiotherapy. After a median follow-up of 11 years (range 1-20), all the patients were alive without evidence of disease, 11 in first complete remission, and 1 after local relapse. In agreement with other reports, the authors underline the unquestionable pivotal role of radical surgery in the treatment of liposarcoma. The high proportion of resectable tumors accounts for the excellent survival of the patients in this study. The role of both adjuvant chemotherapy and radiotherapy is uncertain and awaits multicentric cooperative prospective studies.

Synovial sarcoma: report of a series of 25 consecutive children from a single institution.

BACKGROUND: The role of postoperative radiotherapy and adjuvant chemotherapy in the treatment of synovial sarcoma remains to be determined. PROCEDURE: Twenty-five children were treated during a 23-year period with a multimodality approach. All of them had resection of the primary tumor (three amputations), followed by surgical retreatment in eight. Postoperative radiotherapy was delivered to 16 patients and adjuvant chemotherapy was given to 22. RESULTS: At the time of the report, 19 patients were alive and without evidence of disease. Six developed distant metastases (one associated with local recurrence); five of them died of their disease and one was alive in complete remission at 4 years from relapse. With a median follow-up of 9 years (range 2-23), the survival and the event-free survival at 5 years were 80% (SE 8.2) and 74% (SE 9.2), respectively. All relapsing patients had been classified as T2B. CONCLUSIONS: Multimodality treatment yielded satisfying survival results using limb-preserving surgery in most cases. Tumor size > 5 cm and invasiveness, which defined stage T2B, were the most important predictors of poor outcome. Evaluation of the role of adjuvant chemotherapy and radiotherapy awaits prospective studies, even if T2B patients, as well as children having nonradical surgery, seem worth managing by adjuvant treatments.

Malignant peripheral nerve sheath tumors in children: a single-institution twenty-year experience.

A retrospective series of pediatric patients with localized malignant peripheral nerve sheath tumors (MPNST) treated during a 20-year period at one institution is reported. Between 1976 and 1996, 24 consecutive children were treated by a multimodality approach. Conservative surgery was the treatment of choice: primary radical surgery was performed in 10. Postoperative radiotherapy was administered in 12 and adjuvant chemotherapy in 19. Eight patients were alive without evidence of disease, six in first complete remission and two in second complete remission, after a median follow-up of 230 months. The 10-year event-free survival (EFS) and survival were 29% and 41%, respectively. Survival was 80% for the patients who underwent radical surgery, and 14% for the others; 71% for patients with tumors smaller than 5 cm, and 29% for those with tumors 5 cm or larger. Local recurrence was the major cause for treatment failure (13 of 17; 76%); the rate of local relapse was 33% v 75% in patients who either received or did not receive radiotherapy. Complete surgical excision remains the most effective treatment for MPNST and represents the main prognostic factor along with tumor size. Radiotherapy seems to play a role in achieving local control, whereas the role of chemotherapy is uncertain.

Intravascular lymphomatosis (IL) in a child mimicking a posterior fossa tumor.

Intravascular lymphomatosis (IL) is a rare entity only recently included in lymphoma classification, whose main feature is the exclusive or predominant growth of neoplastic cells within blood vessels. The vast majority of the patients affected by IL belong to the 7th or 8th decade of life and present with skin rash or CNS diffuse necrotic or demyelinating lesions. Case report. SS, a 13-year-old girl, was admitted to a Neurosurgery Unit because of endocranic hypertension, where, after CT and MRI documenting a IV ventricle 3 cm diameter tumor, she was submitted to complete tumor excision: extemporary diagnosis was suggestive of medulloblastoma. When referred to us she had persistent fever with normal blood and spinal fluid cultures. Whole CNS MRI did not give evidence of residual or metastatic disease while CSF cytology showed only pleiocytosis. Treatment was started according to our ongoing protocol for medulloblastoma with pre-radiation chemotherapy. Before delivering radiotherapy (RT), upon review of histologic specimens, the definitive diagnosis of IL B-phenotype was made. The girl was re-admitted and, after a complete re-staging, chemotherapy was intensified according to our schedule for high-grade B-cell lymphoma and CNS was irradiated up to a total dose of 25 Gy. She remained alive in continuous complete remission at 21 months after diagnosis. The case here reported is unique for age, tumor presentation, and, so far, favourable outcome, in spite of the delayed histological diagnosis.

Undifferentiated nasopharyngeal carcinoma in children and adolescents: comparison between staging systems.

BACKGROUND: New criteria for classifying nasopharyngeal carcinoma were defined in the 5th edition of the American Joint Committee on Cancer (AJCC) staging manual. We investigated the clinical implications of the new system by comparing it with the 4th edition in a cohort of pediatric undifferentiated nasopharyngeal carcinoma (UNPC). PATIENTS AND METHODS: We retrospectively restaged 54 patients younger than 17 years who had biopsy-proven UNPC, treated between 1965 and 1999 in a single institution. RESULTS: Using the 5th edition an overall downstaging of the population according to T status, N status, and stage grouping was evident along with a better correlation with likelihood of survival. The comparison between local and advanced disease according to T stage (T1+T2 vs. T3+T4) became highly significant in the new system (P = 0.0011 vs. P = 0.067 in the 4th edition). CONCLUSIONS: As far as prognostic categories are concerned, the 5th edition of the AJCC staging manual appears to be an improvement over the previous classification, even though for pediatric patients a uniform distribution among stages cannot be observed because most children present with advanced disease. The overall downstaging should be taken into consideration for the stratification of patients in future trials.

Effects of recombinant human granulocyte-macrophage colony-stimulating factor in an intensive treatment program for children with Ewing's sarcoma.

BACKGROUND AND OBJECTIVES: A treatment program including polychemotherapy at progressively escalating doses and sequential hemi-body irradiation (HBI) was adopted between 1987-1994 at our Pediatric Unit for high risk Ewing's sarcoma. Granulocyte-macrophage colony-stimulating factor (GM-CSF) was added to the treatment program in a phase II study fashion to evaluate, in a pediatric setting, its tolerability, as well as its impact on drug dose escalation and on the need for supportive care. DESIGN AND METHODS: The study was open-label and sequential; GM-CSF administration (5 microg/Kg s.c./d x10) was planned after each chemotherapy cycle and after each HBI session in 18 consecutive patients (group A). Thirty-eight additional patients (group B) were treated by the same therapeutic program, without GM-CSF. In 12 patients (6 in each group) long-term bone marrow cultures (LTBMC) were performed to evaluate the myeloproliferative potential throughout the chemotherapeutic program. RESULTS: Seven of 18 (39%) patients experienced side effects from GM-CSF; 3/7 discontinued GM-CSF due to anaphylactic symptoms. The degree of neutropenia, as well as the frequency of infectious episodes and the need for supportive care were significantly lower in group A than in group B. Iatrogenic thrombocytopenia, and the possibility of performing drug-dose escalation were similar in the two groups. The 5-year event-free survival probabilities for group A and B were similar. LTBMC showed that the chemotherapy-related depletion of myeloid precursors could be more pronounced in patients receiving GM-CSF cyclically. INTERPRETATION AND CONCLUSIONS: In this series, GM-CSF was shown to be effective on iatrogenic neutropenia and related complications, with no impact on thrombopoiesis, drug dose escalation and outcome.