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Vienna, Austria

Burkhardt B.,Justus Liebig University | Oschlies I.,University of Kiel | Klapper W.,University of Kiel | Zimmermann M.,Justus Liebig University | And 7 more authors.
Leukemia | Year: 2011

Age-related differences in the distribution, biology and treatment response of non-Hodgkin's lymphoma (NHL) in adolescents remain to be elucidated. The current analyses present clinical parameters and outcomes of adolescents treated in pediatric NHL-BFM trials. Patients were stratified by histological subtype: lymphoblastic lymphoma (LBL); mature B-NHL, including Burkitt's lymphoma/leukemia (BL/B-AL), diffuse B-cell lymphoma (DLBCL-CB) and mediastinal B-cell lymphoma (PMLBL); and anaplastic large cell lymphoma (ALCL). Between October 1986 and December 2007, 2915 patients were registered, including 378 (13%) adolescents (15-18 years) with BL/B-AL (n101), ALCL (n74), DLBCL-CB (n55), T-LBL (n45), PMLBL (n24), pB-LBL (n13) and rare or not-specified NHL subtypes (n66). The 5-year event-free survival (EFS) was 792% for adolescents compared with 851% for patients aged 15 years (P0.014). EFS was 837% for adolescents with T-LBL, 824% with BL/B-AL, 855% with DLBCL-CB, 5710% with PMLBL and 706% with ALCL. According to sex, the 5-year EFS in females versus males, respectively, was 705 versus 832% overall (P0.004), 5717 versus 926% (P0.0036) for T-LBL patients and 719 versus 973% (P0.0067) for DLBCL-CB patients. Adolescents with NHL treated according to pediatric NHL-BFM protocols had an EFS of 792%, which is marginally inferior to that of children. In adolescents with T-LBL and DLBCL-CB, female sex was associated with a worse prognosis. © 2011 Macmillan Publishers Limited All rights reserved.

Trottestam H.,Karolinska University Hospital | Horne A.,Karolinska University Hospital | Arico M.,Azienda Ospedaliero Universitaria A. Meyer | Egeler R.M.,Leiden University | And 7 more authors.
Blood | Year: 2011

Hemophagocytic lymphohistiocytosis (HLH) used to have a dismal prognosis.We report the final results of HLH-94, the largest prospective diagnostic/therapeutic HLH study so far. The treatment includes immunosuppressive and cytotoxic therapy aiming at clinical remission, followed by HSCT in patients with familial, persistent, or recurrent disease. Altogether, 249 patients fulfilled inclusion criteria and started HLH-94 therapy (July 1994-December 2003); 227 (91%) were followed-up for ≥ 5 years. At 6.2 years median follow-up, estimated 5-year probability of survival was 54% ± 6%. Seventy-two patients (29%) died before HSCT, 64 within 1 year, 97% of whom had active disease. In 124 patients who underwent HSCT, 5-year survival was 66 ± 8%; tendency to increased survival (P = .064) in patients with nonactive disease at HSCT. Patients with familial disease had a 5-year survival of 50% ± 13%; none survived without HSCT. Patients deceased during the first 2 months more often had jaundice, edema, and elevated creatinine. Forty-nine patients (20%) were alive without signs of HLH activity and off-therapy > 1-year without HSCT; they presented at older age (P<.001), weremoreoften female (P=.011), and less often had CNS disease (P < .001) or hepatomegaly (P = .007). To conclude, HLH-94 chemoimmunotherapy has considerably improved outcome in HLH. Collaborative efforts are needed to further reduce early mortality, HSCT-related mortality, and neurologic late effects. © 2011 by The American Society of Hematology.

Harrison C.J.,Northumbria University | Haas O.,St. Anna Childrens Hospital | Harbott J.,Justus Liebig University | Biondi A.,University of Milan Bicocca | And 3 more authors.
British Journal of Haematology | Year: 2010

Treatment of childhood acute lymphoblastic leukaemia (ALL) has improved considerably in recent years. A contributing factor has been the improved stratification for treatment according to a number of factors, including genetic determinants of outcome. Here we review the current diagnostic criteria of genetic abnormalities in precursor B-ALL (BCP-ALL), including the relevant technical approaches and the application of the most appropriate methods for the detection of each abnormality. The abnormalities with the most significant impact for treatment and management of BCP-ALL are t(9;22)(q34;q11)/BCR-ABL1, t(4;11)(q21;q23)/MLL-AFF1 and near-haploidy/low hypodiploidy for high risk stratification and, to a lesser extent, t(12;21)(p13;q22)/ETV6-RUNX1 and high hyperdiploidy for good risk management. Apart from the numerical abnormalities, these can be routinely tested for by reverse transcription polymerase chain reaction, providing a basic yet informative screen. However, cytogenetics, particularly fluorescence in situ hybridization may provide reliable alternative detection methods dependent upon the preferred technical approach within each protocol. © 2010 Blackwell Publishing Ltd.

Pulsipher M.A.,University of Utah | Peters C.,St. Anna Childrens Hospital | Pui C.-H.,St Jude Childrens Research Hospital
Biology of Blood and Marrow Transplantation | Year: 2011

Because survival with both chemotherapy and allogeneic hematopoietic stem cell transplantation (HSCT) approaches to high-risk pediatric acute lymphoblastic leukemia (ALL) generally improves through the years, regular comparisons of outcomes with either approach for a given indication are needed to decide when HSCT is indicated. Improvements in risk classification are allowing clinicians to identify patients at high risk for relapse early in their course of therapy. Whether patients defined as high risk by new methods will benefit from HSCT requires careful testing. Standardization and improvement of transplant approaches has led to equivalent survival outcomes with matched sibling and well-matched unrelated donors; however, survival using mismatched and haploidentical donors is generally worse. Trials comparing chemotherapy and HSCT must obtain sufficient data about therapy and stratify the analysis to assess the outcomes of best-chemotherapy with best-HSCT approaches. © 2011 American Society for Blood and Marrow Transplantation.

Minkov M.,St. Anna Childrens Hospital
Pediatric Drugs | Year: 2011

Langerhans cell histiocytosis (LCH) is a rare (about 35 cases per million children aged 014 years), non-malignant disease characterized by proliferation and accumulation of clonal dendritic cells, extreme clinical heterogeneity, and an unpredictable course. Three large-scale, international, prospective therapeutic studies (LCH-I to III) for multisystem LCH (MS-LCH) have been conducted by the Histiocyte Society since 1991. The cumulative lessons from these studies are summarized in this review. Patients with MS-LCH represent a heterogeneous group with respect to disease severity and outcome, therefore treatment stratification and risk-tailored treatment are mandatory. The risk for mortality can be predicted based on involvement of 'risk organs' (e.g. hematopoietic system, liver, andor spleen) at diagnosis and on response to initial therapy (assessed after 612 weeks of treatment). Thus, patients without involvement of risk organs (low-risk group) are not at risk for mortality but need systemic therapy in order to control the disease activity and avoid reactivations and permanent consequences. Patients with risk organ involvement (risk group) are at risk for mortality, and lack of therapy response defines a subgroup with a particularly dismal prognosis (high-risk group). Those patients in the risk group who respond to therapy and survive are at risk for reactivations and permanent consequences.The LCH-I study compared the efficacy of vinblastine and etoposide, and concluded that they are equivalent single-agent treatments for children with MS-LCH. However, the results of this trial were inferior with respect to response rate at week 6, disease reactivation rate, and sequelae, when compared with historical trials using more intensive regimens. The combination of prednisolone and vinblastine was established as a standard first-line treatment through the LCH-II and LCH-III studies. The regimen consists of one to two 6-week courses (continuous oral corticosteroids 40mgm2day for 4 weeks, tapered over 2 weeks plus weekly vinblastine intravenous push) of initial therapy, followed by a continuation phase (three weekly pulses of oral prednisolone 40mgm2day for 5 days plus a vinblastine injection). The addition of a third drug to the standard combination (etoposide in LCH-II and methotrexate in LCH-III) failed to significantly improve survival in the risk group. The remaining mortality in the risk group is about 20, and up to 40 in the high-risk group. Concerning low-risk MS-LCH, comparison of results of the LCH-II study with historical data suggested that the remaining reactivation rate of about 50 (and possibly permanent consequences) could be reduced by prolongation of the total treatment duration. To study this hypothesis, in the low-risk group of the LCH-III study standard maintenance therapy was randomly given for a total treatment duration of 6 and 12 months. Unpublished preliminary data from this recently closed trial suggested that prolongation of the treatment duration may significantly improve reactivation-free survival.In summary, several studies have shown that systemic therapy is indicated for all patients with MS-LCH. A standard two-drug regimen consisting of an initial 'intensive' phase for 612 weeks, followed by a less intensive 'maintenance phase' for a total treatment duration of at least 12 months is recommended for patients treated outside of clinical trials. Non-responders, particularly those with progressive disease in risk organs, are eligible for experimental salvage approaches. Remaining questions will be addressed in the upcoming LCH-IV trial, which is in the process of intensive preparation. © 2011 Adis Data Information BV. All rights reserved.

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