S. Sauter

In trial ALL-BFM 86, the largest multicenter trial of the Berlin-Frankfurt-Münster (BFM) study group for childhood acute lymphoblastic leukemia (ALL), treatment response was used as an overriding stratification factor for the first time. In the previous trial ALL-BFM 83, the in vivo response to initial prednisone treatment was evaluated prospectively. A blast cell count of > or = 1,000/microL peripheral blood after a 7-day exposure to prednisone and one intrathecal dose of methotrexate (MTX) identified 10% of the patients as having a significantly worse prognosis. In trial ALL-BFM 86 patients with > or = 1,000/microL blood blasts on day 8 were included in an experimental branch EG. Patients with < 1,000/microL blood blasts on day 8 were stratified by their leukemic cell burden into two branches, Standard Risk Group (SRG) and Risk Group (RG). SRG patients received an eight-drug induction followed by consolidation protocol M (6-mercaptopurine, high-dose [HD] MTX 4 x 5 g/m2) and maintenance. RG patients were treated with an additional eight-drug reinduction element. For EG patients protocol M was replaced by protocol E (prednisone, HD-MTX, HD-cytarabine, ifosfamide, mitoxantrone). All patients received intrathecal MTX therapy; only those of branches RG and EG received cranial irradiation. In branch RG, patients were randomized to receive or not to receive late intensification (prednisone, vindesine, teniposide, ifosfamide, HD-cytarabine) in the 13th month. During the trial reinduction therapy was introduced in branch SRG, because in the follow-up of trial ALL-BFM 83 the randomized low-risk patients receiving reinduction did significantly better. Nine hundred ninety-eight evaluable patients were enrolled, 28.6% in SRG, 61.1% in RG, 10.3% in EG. At a median follow-up of 5.0 (range 3.4 to 6.9) years, the estimated 6-year event-free survival was 72% +/- 2% for the study population, 58% +/- 5% in branch SRG for the first 110 patients without reinduction therapy, 87% +/- 3% for the next 175 patients with reinduction therapy, 75% +/- 2% in branch RG, and 48% +/- 5% in branch EG. Late intensification did not significantly affect treatment outcome of RG patients; however, only 23% of the eligible patients were randomized. Prednisone poor response remained a negative prognostic parameter despite intensified therapy. The results confirmed the benefit of intensive reinduction therapy even for low-risk patients. The strategy of induction, consolidation, and intensive reinduction may offer roughly 75% of unselected childhood ALL patients the chance for an event-free survival.

PURPOSE To prove the efficacy of a treatment stratified according to histology for children with non-Hodgkin's lymphoma (NHL), including acute B-cell leukemia (B-ALL). PATIENTS AND METHODS From October 1986 to March 1990, 302 assessable patients, 0.6 to 17.8 years of age, with newly diagnosed NHL were enrolled onto study ALL/NHL-BFM 86. Fifty percent of patients had Burkitt-type lymphomas, including B-ALL; 24% had lymphoblastic lymphoma; 18% had diffuse large-cell lymphoma; and 8% had an NHL not further classified. Therapy group B included Burkitt's-type lymphomas, B-ALL, and most large-cell lymphomas including Ki-1 anaplastic large-cell lymphoma. Patients with stage I and II disease resected received three, while all others received six, 5-day therapy courses (dexamethasone, methotrexate [MTX] 0.5 g/m2 [5 g/m2 for stage IV and B-ALL], and intrathecal [IT] therapy in each course, plus ifosfamide, cytarabine, and etoposide alternating with cyclophosphamide and doxorubicin). Therapy for group non-B patients (lymphoblastic lymphoma and pleomorphic T-cell lymphoma [PTCL]) consisted of a Berlin-Frankfurt-Münster (BFM) acute lymphoblastic leukemia protocol, including cranial irradiation for advanced stage. Local therapy was restricted to patients with incomplete tumor regression. RESULTS The probabilities of event-free survival (pEFS) at 7 years were 80% +/- 2% for the whole group, 81% +/- 3% for group B (n = 225), and 78% +/- 5% for group non-B (n = 77) with a follow-up duration of 3.6 to 7 years (median 5 years). Treatment results were comparable between NHL subtypes, except for PTCL, in which three of four patients suffered from relapse. Local disease manifestations were the most frequent site of failure. CONCLUSION This therapy strategy provided patients of all NHL subtypes with an equally high chance to survive event-free, except patients with PTCL. With reduced systemic failure, local tumor control may become more important.

In the ongoing trial ALL-BFM 90 for the treatment of childhood non-B cell acute lymphoblastic leukemia (ALL) 1468 unselected patients (pts) were enrolled from 84 centers in Germany and Switzerland from 4/90 to 12/93. Based on the results of the previous trial ALL/NHL-BFM 86 this treatment program focused especially on therapy modifications for average (MRG) and high risk (HRG) pts, on the evaluation of therapy response for prognosis, and on the identification of high risk pts by molecular genetics. For average risk pts consolidation therapy was intensified by the addition of L-asparaginase (L-ASP) on a randomized basis. In HRG induction and consolidation therapy was modified by introduction of early intensification elements that had proved to be effective in relapsed pts. This patient group was randomized for the evaluation of the effects of G-CSF administered in the intervals between the intensification elements. Distribution of the 1376 eligible pts into the three treatment arms SRG (standard risk), MRG, and HRG was as expected (17 pts not yet assigned): 385 pts (28.0%), 834 pts (60.6%), and 140 pts (10.2%), respectively. Treatment consisted of the 8-drug induction (Protocol I), consolidation (Protocol M), reinduction (Protocol II), and maintenance therapy (total therapy duration 24 months). The drug doses and combinations were only slightly modified compared to the previous study ALL-BFM 86 with the exception of the randomized L-ASP containing arm MRG-2 (Protocol M-A) and group HRG. Preventive cranial irradiation was reduced to 12 Gy and applied to MRG and HRG pts only. As in study ALL-BFM 86, the initial response to a 7-day exposure to prednisone and to the first intrathecal injection of MTX at diagnosis was evaluated at day 8 of treatment with regard to blast count in peripheral blood (PB). In addition, pts were now investigated for the presence of blasts in the bone marrow (BM) at day 15 of treatment to compare the prognostic power of both response parameters. Identification of translocation t(9; 22) and/or BCR-ABL rearrangement characterized a small subgroup of pts that were not detected by poor initial therapy response. These pts were enrolled in HRG for more intensive treatment including allogeneic bone marrow transplantation (BMT). After a median observation time of 22 months, the overall probability for event-free survival (p-EFS) is 82 +/- 2%. 11 pts (0.8%) died before complete remission (CR) was achieved, 15 pts (1.1%) died while in CR for reasons other than relapse.(ABSTRACT TRUNCATED AT 400 WORDS)

OBJECTIVE: In recent years, psycho-oncology has focused more and more on adolescents and young adults with cancer (AYA). Many studies have concentrated on fertility issues in AYAs, but romantic relationships and sexuality have only been researched to a limited extent. This cross-sectional study examined AYAs' quality of relationships and sexuality satisfaction thereby identifying sex differences. METHODS: Ninety-nine cancer patients (N = 33 males) diagnosed between 15 and 39 years who were in a romantic relationship at the time of the survey completed questionnaires on their relationship (Partnership Questionnaire), sexuality (Life Satisfaction Questionnaire), and sexuality needs (Supportive Care Needs Survey). Test for mean differences and regression analyses to determine associated variables were performed. RESULTS: Seventy-six percent of AYAs (N = 75) rated their relationship quality as high. About 64% of patients reported having less sexual intercourse since diagnosis, more women than men (72% vs. 45%; p = .011). The need for support was strongest for changes in sexual feelings (N = 38; 38.3%). Duration of relationship (β = -0.224), being on sick leave (β = 0.325), and satisfaction with sexuality (β = 0.409) were associated with satisfaction with relationship (R(2) = 0.256). Satisfaction with sexuality (R(2) = 0.344) was regressed on physical function (β = 0.419), satisfaction with relationship (β = 0.428), and male gender (β = -0.175). Sexuality need (R(2) = 0.436) was associated with fatigue (β = 0.232) and satisfaction with sexuality (β = -0.522). CONCLUSION: Although they reported high satisfaction with their relationships, AYA patients experienced sexual problems and need support with sexual issues. As a substantial proportion of patients felt stressed because of sexual changes, communication and interventions addressing post-cancer sexuality, particularly in women, are indicated.

Purpose: Although cancer often impacts work issues in patients, little is known about changes in the employment situation of adolescent and young adult (AYA) cancer survivors. Materials and Methods: We surveyed AYA cancer patients (18–39 years at diagnosis, diagnosis ≤4 years) using as set of validated self-report measures. By using multivariate and regression analyses, we analyzed employment status prediagnosis (in retrospect) and return to work (RTW) rate about 2 years postcancer diagnosis and related predictors. We compared work-related characteristics (occupational position, weekly working hours, and type of employment contract) at both time points. Cancer-related financial distress (European Organization for Research Treatment of Cancer–Quality of Life Questionnaire [EORTC QLQ-C30]) was assessed. Results: A total of 505 AYAs (mean age at diagnosis 29.7 years) completed the questionnaire. After an average of 2 years postcancer diagnosis, 83.4% among those being employed at the time of diagnosis (n = 355) had returned to work, 2.8% were on vocational training, 4.5% were unemployed, 4.2% were disabled due to reduced work capacity, and 5.1% were not employed for other reasons. For 158 of 505 AYAs (31.3%), employment status had changed since diagnosis. Significant changes of work-related characteristics were found for the weekly working hours (Matdiagnosis = 35.8; standard deviation [SD] = 7.4; Mt2 = 34.7; SD = 8.2; p = 0.004). Twenty-four percent of the RTW patients and 68% of patients not RTW reported cancer-related financial distress. Patients with comorbid diseases, having hematological cancer or sarcoma, were less likely to RTW. Conclusion: Most AYAs returned to work in the medium term, often by reducing weekly working hours. Since AYAs state significant cancer-related financial distress, even after RTW, it seems particularly relevant to provide financial support and occupational counseling.