Biomedical subjects

W A Kamps

Publications and source records attributed to W A Kamps.

At least 19 recordsLinked to original sources

PubMed2006

Health-related quality of life and adverse late effects in adult (very) long-term childhood cancer survivors.

PURPOSE METHOD: The RAND-36 was used to assess HRQoL in all adult (> or =18 years) survivors who had attended the long-term follow-up clinic since 1995. The survivors were divided into two groups based on the length of follow-up: Group LF (long term follow-up, follow-up > or =20 years, n=129) and Group VLF (very long-term follow-up, follow-up >20 years, n=184). Data on diagnosis, treatment and complications were obtained from medical records. Late effects were graded using the CTCAEv3. RESULTS: The RAND-36 was completed by 313 (86.2%) out of 363 eligible patients. Except for higher scores on the subscale Bodily pain, LF patients did not differ significantly on the RAND-36 subscales from the population sample; VLF patients had significant lower scores on the subscales Physical functioning (P=0.003), Social functioning, Vitality and General health perception (P<0.001). Significantly more VLF patients (P<0.001) had severe (grade 3 and 4) late effects (47.8%) compared to LF patients (27.9%). Female gender and especially psycho-social late effects were inversely related to HRQoL. CONCLUSION: Childhood cancer survivors who were diagnosed more than 20 years ago have lower scores on the RAND 36, and have significantly more severe late effects than those diagnosed more recently. Patients with longer follow-up are more likely to become lost to follow-up. Time has come to establish new models of care for adult childhood cancer survivors, which are more flexible and appropriate to the needs of adult childhood cancer survivors.

Adult↗

PubMed2006

Long-term cardiac follow-up in survivors of a malignant bone tumour.

BACKGROUND: Longitudinal studies of cardiac function in long-term childhood cancer survivors are scarce and frequently concern a median follow-up shorter than 13 years. PATIENTS AND METHODS: Cardiac assessment was performed in 22 doxorubicin-treated long-term survivors of a malignant bone tumour at median 22 years (range 15-27.5) post-treatment. Age at follow-up was 39 years (range 27-59) and cumulative dose of doxorubicin was 360 mg/m(2) (range 225-550). Cardiac function was assessed by echocardiography and (24-h) ECG. The results were compared with those of earlier assessments at 9 years (1992) and 14 years (1997) post-treatment. RESULTS: Systolic dysfunction was found in 27% (9% in 1997; P = 0.02) and diastolic dysfunction in 45% (18% in 1997; P = 0.02). Heart rate variability showed further deterioration compared with earlier results. CONCLUSIONS: Twenty-two years after doxorubicin-treatment, bone tumour survivors showed progressive cardiac dysfunction.

Adolescent↗

PubMed2006

Imminent ovarian failure in childhood cancer survivors.

The aim of this study was to investigate reproductive history and the prevalence of imminent ovarian failure (IOF) in female childhood cancer survivors. Reproductive history and ovarian function were evaluated by questionnaires (n=124) and by measurement of follicle stimulating hormone (FSH) and oestradiol (E2) levels (n=93). IOF was defined as FSH>10 IU/l or E2>0.28 nmol/l on day 3 of the menstrual cycle, or FSH>12.4 IU/l on day 7 of the pill-free interval. IOF was demonstrated in 22.6% of the participants and correlated with age at diagnosis (P<0.005) and age at study (P=0.036). IOF correlated inversely with methotrexate (P=0.046). The incidence of miscarriages (22.7%) and recurrent miscarriages (7.3%) was increased. The male/female (M/F) ratio of the offspring was decreased. In conclusion, female childhood cancer survivors are at risk for IOF. If pregnant, the risk of (recurrent) miscarriages is increased. The M/F ratio in the offspring is decreased.

Abortion, Spontaneous↗

PubMed2006

Leukaemia incidence and survival in children and adolescents in Europe during 1978-1997. Report from the Automated Childhood Cancer Information System project.

Leukaemias constitute approximately one-third of cancers in children (age 0-14 years) and 10% in adolescents (age 15-19 years). Geographical patterns (1988-1997) and time trends (1978-1997) of incidence and survival from leukaemias in children (n=29,239) and adolescents (n=1929) were derived from the ACCIS database, including data from 62 cancer registries in 19 countries across Europe. The overall incidence rate of leukaemia in children was 44 per million person-years during 1988-1997. Lymphoid leukaemia (LL) accounted for 81%, acute non-lymphocytic leukaemia (ANLL) for 15%, chronic myeloid leukaemia (CML) for 1.5% and unspecified leukaemia for 1.3% of cases. Adjusted for sex and age, incidence of childhood LL was significantly lower in the East and higher in the North than in the British Isles. The overall incidence among adolescents was 22.6 per million person-years. The incidence of LL was rising in children (0.6% per year) and adolescents (1.9% per year). During 1988-1997 5-year survival of children with leukaemias was 73% (95% CI 72-74) and approximately 44% for infants and adolescents. Similar differences in survival between children and adolescents were observed for LL, much less so for ANLL. Survival differed between regions; prognosis was better in the North and West than the East. Remarkable improvements in survival occurred in most of the subgroups of patients defined by diagnostic subgroup, age, sex and geographic categories during the period 1978-1997. For children with ANLL most improvements in survival were observed in the 1990s.

Adolescent↗

PubMed2005

Reduction of adult height in childhood acute lymphoblastic leukemia survivors after prophylactic cranial irradiation.

BACKGROUND: Impaired linear growth is a well-recognized complication in long-term childhood ALL survivors who received cranial irradiation. However, as many patients achieve a final height between the 5th and the 95th centile, the true incidence of linear growth impairment might be underestimated. METHODS: Reduction of adult height (RAH) was estimated in adult childhood ALL survivors with and without cranial irradiation. RAH was calculated as the difference between target height (TH) and final height (FH). TH was calculated according to the formula TH = {[(height father + height mother +/- 12)/2] + 3}. RAH was assessed in 79 adult childhood ALL survivors in first complete remission who had received cranial irradiation 25 Gy (Group I, n = 53), 18 Gy (Group II, n = 10) or chemotherapy alone (controls, n = 16). RESULTS: RAH was 8.6 +/- 8.2 cm in Group I (P = 0.001 vs. controls), 6.2 +/- 3.2 cm in Group II (P = 0.01 vs. controls), and 1.7 +/- 4.6 in controls (chemotherapy only). There was no significant difference between Group I and Group II. In Group I females had more RAH than males (P = 0.02). RAH was related to younger age at diagnosis (P = 0.001). CONCLUSIONS: The deficit between target height and final height highlights the reduction of adult height in the majority of male and female childhood ALL survivors who had received prophylactic cranial irradiation, in particular in those who were diagnosed at a younger age. This reduction would have been masked if patients FH was only compared with standard methods. RAH might be a sensitive predictor for growth hormone deficiency as these results suggest that radiation-induced growth hormone deficiency in these patients is the rule rather than the exception.

Adolescent↗

PubMed2005

Causes of death--other than progressive leukemia--in childhood acute lymphoblastic (ALL) and myeloid leukemia (AML): the Dutch Childhood Oncology Group experience.

We analyzed causes of death, other than resistant disease or relapse, in 875 children with acute lymphoblastic leukemia (ALL) and 229 with acute myeloid leukemia (AML), treated on three different Dutch Childhood Oncology Group (DCOG) ALL and three AML protocols. Overall, 23 (2.6%) ALL and 44 (19.2%) AML patients died. Early death (ED, before remission was reached) occurred in nine ALL (1%) and thirty AML (13.1%) patients, including three and ten deaths before treatment was initiated. Chemotherapy-related mortality in remission (CRM) occurred in nine ALL (1.1%) and eight AML (4.4%) patients. For ALL, both ED and CRM declined over time, although this was not statistically significant. For AML a decrease in ED was observed (from 26% to approximately 10%), but counter-balanced by an increase in CRM (from 3 to 8%), maybe related to the scheduling of intensification blocks in AML-92/94. Including transplant-related mortality, death in CR rates in AML increased from 3 to 15% in the last study. The main cause of ED was hemorrhage, often associated with hyperleucocytosis, and infection for CRM. We conclude that mortality dropped favorably in ALL, but not in AML. Especially for AML, effective but less toxic therapy and better supportive care guidelines need to be developed.

Acute Disease↗

PubMed2005

Feasibility of neuropsychological assessment in leukaemia patients shortly after diagnosis: directions for future prospective research.

AIMS: To study neuropsychological functioning of newly diagnosed children with acute lymphoblastic leukaemia (ALL) within two weeks after diagnosis in order to determine the feasibility of a sibling controlled prospective study design. METHODS: Fifty consecutive patients (median age at testing 6.6 years, range 4-12) were included in a prospective, longitudinal, nationwide study. Treatment would include intrathecal and systemic chemotherapy according to the DCLSG ALL-9 protocol. Children were evaluated with an extensive neuropsychological battery including measures of intelligence, memory, attention, language, visual-constructive function, and fine-motor abilities within two weeks after start of the chemotherapy. The control group consisted of 29 healthy siblings (median age at testing 8.2 years, range 4-12), who were tested <4 weeks after the patients' assessment. RESULTS: Mean scores on Wechsler Intelligence Scales did not differ significantly between patients and siblings; mean IQ scores for both the patients and the controls were high average. To examine specific neuropsychological functions, norm scores based on the exact age were acquired by fitting procedures, but no significant differences were found. CONCLUSIONS: Neuropsychological assessment of patients during early hospitalisation is feasible. The results indicate no adverse effect of illness and psychological factors on IQ and neuropsychological functioning of patients with recently diagnosed ALL. The prospective design of this study of cognitive late effects of chemotherapy will allow discrimination between adverse sequelae of disease and treatment.

Child↗

PubMed2005

High expression of Mcl-1 in ALK positive and negative anaplastic large cell lymphoma.

AIM: To gain more insight into the genes involved in the aetiology and pathogenesis of anaplastic large cell lymphoma (ALCL). METHODS: Serial analysis of gene expression (SAGE) was undertaken on the CD4+ALK+ (anaplastic lymphoma kinase positive) ALCL derived cell line Karpas299 and as comparison on CD4+ T cells. Quantitative reverse transcription polymerase chain reaction (RT-PCR) and immunohistochemistry were performed on five ALCL derived cell lines and 32 tissue samples to confirm the SAGE data. RESULTS: High expression of Mcl-1 was seen in the Karpas299 cell line, whereas the two other antiapoptotic Bcl-2 family members, Bcl-2 and Bcl-X(L), were not detected in the SAGE library. Quantitative RT-PCR confirmed the high expression of Mcl-1 mRNA and low expression of Bcl-2 and Bcl-X(L) in Karpas299 and in four other ALCL cell lines. To expand on these initial observations, primary tissue samples were analysed for Mcl-1, Bcl-X(L), and Bcl-2 by immunohistochemistry. All 23 ALK+ and nine ALK- ALCL cases were positive for Mcl-1. Bcl-2 and Bcl-X(L) were expressed infrequently in ALK+ ALCL cases, but were present in a higher proportion of ALK- ALCL cases. CONCLUSION: The consistent high expression of Mcl-1 in ALK+ and ALK- ALCL suggests that Mcl-1 is the main antiapoptotic protein in this disease. The high frequency of Mcl-1, Bcl-2, and Bcl-X(L) positive ALCL cases in the ALK- group compared with the ALK+ group indicates that ALK induced STAT3 activation is not the main regulatory pathway in ALCL.

Anaplastic Lymphoma Kinase↗

PubMed2004

Chemotherapy affects the pattern of failure after shear loading of the proximal tibial growth plate.

INTRODUCTION: Tibial bones are shorter and less resistant to shear forces after treatment with doxorubicin, methotrexate, or cisplatin. We investigated the pattern of failure after shear loading of the proximal tibial growth plate in rats treated with these chemotherapeutic agents. MATERIALS AND METHODS: Male Wistar rats from the age of 4 weeks were given doxorubicin intravenously at 15 mg/m2 body surface area (BSA), methotrexate 60 mg/m2 BSA, or cisplatin 7.5 mg/m2 BSA. There was one nontreated control group fed ad libitum an d a diet control group for each drug-treated group. At the age of 13 weeks the tibial bones were dissected. The proximal growth plate was shear loaded to failure in the posteroanterior direction. The pattern of failure through the growth plate was examined. RESULTS: In rats fed ad libitum the failure pattern ran mainly through the transitional zone between proliferating and hypertrophic chondrocytes, but the pattern of failure showed considerable variability. The pattern in rats treated with methotrexate or cisplatin and that in their diet controls were comparable. In rats treated with doxorubicin the fracture ran mainly through the trabecular zone. CONCLUSIONS: Doxorubicin affects the pattern of failure after shear loading of the proximal tibial growth plate, but methotrexate and cisplatin do not. Special attention should be paid to epiphyseal injuries in children treated with doxorubicin.

Animals↗

PubMed2004

[A cavernous haemangioma of the colon as the cause of rectal bleeding in childhood].

A 13-year-old girl presented with rectal bleeding, abdominal pain and a palpable mass in the lower right abdomen. The history mentioned a chronic anaemia since she was 2 years old. Further examination did not give any indications for inflammation as etiological factor and showed a thickening of (apparently) the small intestine. A laparotomy was performed, since the age and presentation made a malignant lymphoma a probable diagnosis. The combination of chronic anaemia and rectal bleeding also suggested a benign vascular malformation. A large cavernous haemangioma of the transverse colon was found. This was resected and the patient fully recovered. Although a haemangioma of the colon is rare, it is important to keep this possibility in mind in the case of rectal bleeding in childhood, especially when other causes of rectal bleeding are excluded. Usually haemangiomas show spontaneous regression, but this is rare in intestinal haemangiomas. Surgical resection is the therapy of choice in the case of a solitary haemangioma.

Adolescent↗

PubMed2004

The possible role of matrix metalloproteinase (MMP)-2 and MMP-9 in cancer, e.g. acute leukemia.

In the past decades, a lot of effort has been put in identifying the role of matrix metalloproteinases (MMPs) in cancer. The main role of MMPs in angiogenesis, tumor growth and metastasis is degradation of extracellular matrix (ECM) and release and/or activation of growth factors through their degradative activity. The degradative activity finally results in cancer progression. MMP-inhibitors (MMPIs) have already been designed and tested, based on the degradative role of MMPs in cancer progression. First clinical trials with MMPIs have been performed with disappointing results, showing that in order to use MMP-inhibition the mechanisms underlying MMP-expression in cancer have to be further elucidated. This paper reviews the mechanisms of MMPs on molecular and cellular level and discusses the role for MMPs and MMP-inhibition in cancer with special focus on acute leukemia.

Acute Disease↗

PubMed2003

Patient stratification based on prednisolone-vincristine-asparaginase resistance profiles in children with acute lymphoblastic leukemia.

PURPOSE: To confirm the prognostic value of a drug resistance profile combining prednisolone, vincristine, and l-asparaginase (PVA) cytotoxicity in an independent group of children with acute lymphoblastic leukemia (ALL) treated with a different protocol and analyzed at longer follow-up compared with our previous study of patients treated according to the Dutch Childhood Leukemia Study Group (DCLSG) ALL VII/VIII protocol. PATIENTS AND METHODS: Drug resistance profiles were determined in 202 children (aged 1 to 18 years) with newly diagnosed ALL who were treated according to the German Cooperative Study Group for Childhood Acute Lymphoblastic Leukemia (COALL)-92 protocol. RESULTS: At a median follow-up of 6.2 years (range, 4.1 to 9.3 years), the 5-year disease-free survival probability (pDFS) rate +/- SE was 69% +/- 7.0%, 83% +/- 4.4%, and 84% +/- 6.8% for patients with resistant (PVA score 7 to 9), intermediate-sensitive (PVA score 5 to 6), and sensitive (SPVA score 3 to 4) profiles, respectively (sensitive and intermediate-sensitive v resistant, P </=.05). Resistant patients were at increased risk of an early event (nonresponse or relapse within 2.5 years of diagnosis) compared with sensitive and intermediate-sensitive patients (P =.03). The profile did not identify patients at higher risk of late relapse, which was also observed for DCLSG ALL-VII/VIII patients now analyzed at a median of 7.5 years of follow-up (range, 4.4 to 10.8 years). Despite being nondiscriminative for late relapses, the resistant profile was still the strongest prognostic factor for COALL-92 patients in a multivariate analysis including known risk factors (P =.07). CONCLUSION: Drug resistance profiles identify patients at higher risk of early treatment failures and may, therefore, be used to improve risk-group stratification of children with ALL.

Adolescent↗

PubMed2003

Routine radiography does not have a role in the diagnostic evaluation of ambulatory adult febrile neutropenic cancer patients.

Cancer patients treated with chemotherapy are susceptible to bacterial infections. When an adult patient presents with febrile neutropenia, standard diagnostic care includes physical examination, laboratory diagnostics, chest X-ray (CXR) and sinus radiography. However, the yield of routine radiography in the diagnostic evaluation of ambulatory adult febrile neutropenic patients with normal findings at their physical examination is questionable. Two CXRs and one sinus X-ray were obtained in 109 and 106 febrile neutropenic episodes after chemotherapy in ambulatory adult patients who had no clinical signs suggesting pulmonary infection or sinusitis. We found that in only two of 109 (1.8%; 95% Confidence Interval (CI): 0.3-5.8%) febrile neutropenic episodes without clinical signs of new pulmonary disease, the CXR showed a consolidation suggesting pneumonia. In addition, in five of 88 (5.7%; 95% CI: 2.2-12.0%) febrile episodes in asymptomatic patients, sinus X-ray suggested sinusitis. In none of these seven episodes was a change of antibiotic therapy necessary. In the absence of clinical signs indicating pneumonia or sinusitis, the yield of CXR and sinus radiography in ambulatory adult cancer patients presenting with febrile neutropenia is minimal; CXR and sinus radiography should no longer be performed on a routine basis.

Adolescent↗

PubMed2003

The effect of chemotherapy on the morphology of the growth plate and metaphysis of the growing skeleton.

AIM: To establish the effect of three single chemotherapeutic agents on the growing skeleton, male Wistar rats were studied. METHODS: From the age of 4 weeks the rats were given iv doxorubicin (DOX) 15 mg/m(2) body surface area (BSA), methotrexate (MTX) 60 mg/m(2) BSA or cisplatin (CDDP) 7.5 mg/m(2) BSA. One non-treated control group was fed ad libitum (ad lib) and for every drug-treated group there was a diet-control group. After dissection at 13 weeks of age, morphology of the proximal tibial growth plate and metaphysis were studied. RESULTS: Compared to the ad lib group, DOX significantly decreased and MTX increased growth plate height (P<0.05). CDDP decreased height of the proliferating layer (P<0.05). Trabecular volume was decreased in the DOX and CDDP treated rats compared to the ad lib group (P=0.054). Compared to the diet control group trabecular bone volume was unaffected in the DOX group and decreased in the MTX and CDDP group (P<0.05). CONCLUSIONS: Doxorubicin causes growth plate thinning, methotrexate increases growth plate height and cisplatin does not affect growth plate height. All three chemotherapeutic agents decrease the trabecular volume of the proximal tibial metaphysis. Part of the effect of DOX, MTX and CDDP is related to the treatment induced malnutrition.

Animals↗

PubMed2003

Endothelial cells are main producers of interleukin 8 through Toll-like receptor 2 and 4 signaling during bacterial infection in leukopenic cancer patients.

Cancer patients who are leukopenic due to chemotherapy are susceptible to bacterial infections. Normally, clinical conditions during bacterial infections are caused by pathogen-associated molecular patterns, which are components that bind to Toll-like receptor (TLR) 2 (TLR-2) and TLR-4 on leukocytes, resulting in the production of inflammatory cytokines. The mechanism of this inflammatory response in cancer patients with diminished numbers of leukocytes is not completely clear. The levels of interleukin 1 beta (IL-1 beta) and tumor necrosis factor alpha measured in the circulation of leukopenic cancer patients are lower than those measured in that of nonleukopenic patients during bacterial infections, whereas plasma interleukin 8 (IL-8) levels show distinct identical increases during bacterial infections in both leukopenic and nonleukopenic patients. Normally, these cytokines are mainly secreted by leukocytes. In cancer patients with bacterial infections and a diminished number of leukocytes, other sources of IL-8 production, such as endothelial cells, might be expected. Endothelial cells instead of leukocytes become the most important producers of IL-8 during bacterial infections in patients with chemotherapy-induced leukopenia through TLR-2 and TLR-4 signaling. Whole blood samples from six cancer patients were stimulated with lipopolysaccharide (LPS), and then IL-8 concentrations in supernatants were measured. Further, human umbilical vein endothelial cells (HUVECs) were incubated with sera from leukopenic cancer patients with or without bacterial infections, and then IL-8 concentrations in supernatants were measured (n = 6). In addition, the same HUVEC experiment was performed with the addition of neutralizing antibodies against TLR-2 and TLR-4. During leukopenia (<10(9) cells/liter), LPS stimulation of whole blood did not result in an increase in IL-8 levels. However, when endothelial cells were incubated with sera from leukopenic cancer patients during bacterial infections, a three- to eightfold increase in IL-8 production was found, compared to the IL-8 production found after incubation with sera from patients without signs of infections. This increase did not reflect a higher level of IL-8 already present in the sera. Further, we demonstrated that IL-8 production induced in endothelial cells by sera from patients with documented gram-negative infections could be reduced significantly by up to 40% when the cells were incubated with neutralizing antibodies against TLR-4 (P = 0.028). The addition of TLR-2 antibodies slightly enhanced the reduction of IL-8 production. These results suggest that during bacterial infections in cancer patients with markedly diminished numbers of leukocytes, endothelial cells become important producers of IL-8 through TLR-4 signaling and, to a lesser extent, TLR-2 signaling.

Adult↗

PubMed2002

Cardiac status in bone tumor survivors up to nearly 19 years after treatment with doxorubicin: a longitudinal study.

BACKGROUND: Longitudinal assessment of cardiac toxicity in anthracycline-treated long-term bone tumor survivors. PROCEDURES: Cardiac status was assessed in 29 patients 14.1 (range 7-18.7) years after treatment with doxorubicin (DOXO) 360 mg/m(2) (median 225-550). The median age of the patients at the time of the study was 32.5 years (range 19.7-52). The evaluation consisted of an electrocardiogram (ECG), 24-hr ambulatory ECG with analysis of heart rate variability (HRV) and echocardiography. The results were compared to those of a study of the same patients that was performed 5 years earlier 8.9 years (range 2.3-14.1) after treatment. [Postma et al.: Med Pediatr Oncol 26:230-237, 1996] RESULTS: We found no progression of ECG abnormalities, arrhythmias, or echocardiographic abnormalities. Females were at risk for reduced contractility (P = 0.006). HRV was significantly reduced compared to age- and sex-matched controls and compared to the previous results. CONCLUSIONS: Anthracycline-related late echocardiographic abnormalities and arrhythmias detected 8.9 years after treatment, showed no further deterioration with ongoing follow-up. However, there was a significant reduction of HRV. This suggests that HRV might be a sensitive test for detection of anthracycline-induced cardiac toxicity.

Adolescent↗

PubMed2002

Fever and neutropenia in cancer patients: the diagnostic role of cytokines in risk assessment strategies.

Cancer patients treated with chemotherapy are susceptible to bacterial infections. Therefore, all neutropenic cancer patients with fever receive standard therapy consisting of broad-spectrum antibiotics and hospitalization. However, febrile neutropenia in cancer patients is often due to other causes than bacterial infections. Therefore, standard therapy should be re-evaluated and new treatment strategies for patients with variable risk for bacterial infection should be considered. This paper reviews the changing spectrum of microorganisms and resistance of microorganisms to antibiotics in infection during neutropenia and discusses new strategies for the selection of patients with low-risk for bacterial infection using clinical and biochemical parameters such as acute phase proteins and cytokines. These low-risk patients may be treated with alternative therapies such as oral antibiotics, early discharge from the hospital or outpatient treatment.

Antineoplastic Agents↗

PubMed2002

BFM-oriented treatment for children with acute lymphoblastic leukemia without cranial irradiation and treatment reduction for standard risk patients: results of DCLSG protocol ALL-8 (1991-1996).

Modern treatment strategies, consisting of intensive chemotherapy and cranial irradiation, have remarkably improved the prognosis for children with acute lymphoblastic leukemia. However, patients with a potential for cure are at risk of severe acute and late adverse effects of treatment. Furthermore, in 25-30% of patients treatment still fails. The objectives of the DCLSG study ALL 8 were to decrease the toxicity and to increase the effectivity of BFM-oriented treatment. Decrease of toxicity was aimed at by confirmation of the results of the previous DCLSG study ALL-7, showing that the majority (94%) of children with ALL can successfully be treated with BFM-oriented therapy without cranial irradiation, and by reduction of treatment for standard risk (SRG) patients. To increase the cure rate in medium risk (MRG) patients the efficacy of high doses of intravenous 6-mercaptopurine (HD-6MP) during protocol M and in SRG patients the efficacy of high doses of L-asparaginase (HD-L-ASP) during maintenance treatment was studied in randomized studies. Patient stratification and treatment were identical to protocol ALL-BFM90, with the following differences: no prophylactic cranial irradiation, SRG patients received only phase 1 of protocol I. Four hundred and sixty-seven patients entered the protocol: 170 SRG, 241 MRG and 56 HRG patients. The 5 years event-free survival rate for all patients was 73% (s.e. 2%); for SRG, MRG and HRG patients 85% (s.e. 3%), 73% (s.e. 3%) and 39% (s.e. 7%), respectively. In patients >1 year of age at diagnosis unfavorable prognostic factors were male sex, >25% blasts in the bone marrow at day 15 and initial white blood cell count (WBC) >50 x 10(9)/l. The cumulative risk of CNS relapse rate was 5% (s.e. 1%) at 5 years. These results confirm that the omission of cranial irradiation in BFM-oriented treatment does not jeopardize the overall good treatment results, nor does early reduction of chemotherapy in SRG patients. No benefit was observed from treatment intensification with HD-L-ASP in SRG patients, nor from HD-6MP in MRG patients.

Antineoplastic Combined Chemotherapy Protocols↗