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ABSTRACT: Prospective trials on neuroblastoma-induced myelopathy are lacking. Therefore, we retrospectively analysed patients in four national neuroblastoma trials.
Neuroblastoma patients diagnosed between August 1989 and December 2008 were included. Clinical and molecular data were available in the national trials database. Additional details on neurological findings, treatment, and outcome were collected using a questionnaire.
Among 2603 patients, 122 (61 males and 61 females) had symptoms of spinal cord compression (SCC), and 99 of these were included in the final long-term analysis. The survival of patients with symptoms of SCC was better than that of patients without symptoms. Patients first presented with lower extremity motor impairment (95%), impaired cutaneous sensibility (58%), neuropathic pain (56%), bladder dysfunction (44%), and/or constipation (34%). Symptoms improved after first-line neurosurgery in 36 out of 52 patients and after first line chemotherapy in 30 out of 47 patients (p=0.77). After a median observation time of 8 years 1 month (range 1mo-19y 6mo), 71 out of 99 patients still had residual impairments: motor impairment (43%), scoliosis (31%), impaired bladder function (26%), constipation (19%), impaired cutaneous sensibility (17%), growth delay (14%), and neuropathic pain (5%). The initial treatment had no clear impact on the frequency of late effects.
This retrospective analysis showed no clear advantage of either first-line neurosurgery or chemotherapy and that most patients still exhibit residual symptoms and require specialized care.
Developmental Medicine & Child Neurology 02/2012; 54(4):347-52. · 2.92 Impact Factor
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Alexander Claviez,
Carme Canals,
Daan Dierickx,
Jerry Stein,
Isabel Badell,
Andrea Pession,
Stephen Mackinnon,
Shimon Slavin,
Jean-Hugues Dalle,
Manuel Jurado Chacón,
Mahmoud Sarhan,
Robert Francis Wynn, Meinolf Suttorp,
Giorgio Dini,
Anna Sureda,
Norbert Schmitz
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ABSTRACT: Ninety-one children and adolescents 18 years or younger after allogeneic hematopoietic stem cell transplantation (HSCT) for relapsed or refractory Hodgkin lymphoma (HL) were analyzed. Fifty-one patients received reduced intensity conditioning (RIC); 40 patients received myeloablative conditioning (MAC). Nonrelapse mortality (NRM) at 1 year was 21% (+/- 4%), with comparable results after RIC or MAC. Probabilities of relapse at 2 and 5 years were 36% (+/- 5%) and 44% (+/- 6%), respectively. RIC was associated with an increased relapse risk compared with MAC; most apparent beginning 9 months after HSCT (P = .01). Progression-free survival (PFS) was 40% (+/- 6%) and 30% (+/- 6%) and overall survival (OS) was 54% (+/- 6%) and 45% (+/- 6%) at 2 and 5 years, respectively. Disease status at HSCT was predictive of PFS in multivariate analysis (P < .001). Beyond 9 months, PFS after RIC was lower compared with MAC (P = .02). Graft-versus-host disease did not affect relapse rate and PFS. In conclusion, children and adolescents with recurring HL show reasonable results with allogeneic HSCT. Especially patients allografted in recent years with good performance status and chemosensitive disease show highly encouraging results (PFS: 60% +/- 27%, OS: 83% +/- 15% at 3 years). Because relapse remains the major cause of treatment failure, additional efforts to improve disease control are necessary.
Blood 07/2009; 114(10):2060-7. · 9.90 Impact Factor
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Ulrike Bacher,
Evgeny Klyuchnikov,
Tatjana Zabelina,
Hellmut Ottinger,
Dietrich W Beelen,
Hubert Schrezenmeier,
Gerhard Ehninger,
Carlheinz Müller,
Jürgen Berger, Meinolf Suttorp,
Hans-Jochem Kolb,
Nicolaus Kröger,
Axel R Zander
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ABSTRACT: Due to the recent changes in the indication to allogeneic stem cell transplantation (SCT) in chronic myeloid leukemia (CML), we retrospectively analyzed 1,716 patients with different CML stages who received an allograft from related (n = 767) or unrelated donors (n = 938) within the German Registry of Stem Cell Transplantation (DRST) from 1998 to 2004. Myeloablative conditioning was performed in 724/871 cases (83%), dose-reduced conditioning in 147/871 (17%). Annual transplantations were decreasing from 357 to 98 (28%) in the period of study, but the proportion of advanced cases was increasing from 32% (112/346) to 53% (50/94) of all SCTs. Stage of disease, intervals from diagnosis, and patients' age were independent prognostic parameters, while peripheral stem cells and unrelated transplantation seemed equal to bone marrow/related transplantation. This study demonstrates that allo-SCT still has an important role in advanced CML, which emphasizes the need for optimized transplantation strategies for these high-risk patients.
Annals of Hematology 04/2009; 88(12):1237-47. · 2.62 Impact Factor
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ABSTRACT: Allogeneic transplantation of peripheral blood progenitor cells (PBPC) markes the general anaesthesia of the donor unnecessary and may result in more rapid engraftment and faster recovery of the immune system. We have studied G-CSF-mediated PBPC mobilization in healthy donors and analysed the cellular composition of the resulting PBPC grafts. PBPC grafts were obtained from nine healthy donors (18-67 years old) for allogeneic or syngeneic transplantation. Six donors received 10 μg/kg G-CSF per day, the others 5-6 μg/kg. Mobilization and harvesting were well tolerated except for moderate bone pain which occurred in all donors primed with 10 μg/kg. With 10 μg/kg, a 31-fold (9-62) enrichment of circulating CD34+ cells was observed with peak values constantly occurring on day 5 after the start of G-CSF administration. Starting harvest on day 5, one to three collections on consecutive days yielded 5.5 x 106/kg (0.9-10.7) CD34+ cells, 219 x 106/kg (106–314) T cells, and 34 x 106/kg (23–67) NK cells per 10 litres leukapheresis volume. Altogether, PBPC grafts contained 3 times more CD34+ cells, 7 times more T cells, and 20 times more NK cells than five allogeneic marrow grafts that were analysed for comparison. The yield of CD34+ cells per 10 litres apheresis volume as well as the height of the CD34+ peak in peripheral blood were inversely correlated to the age of the donor. In the donors primed with 5–6μg/kg G-CSF the increase of circulating CD34+ cells (4–7-fold enrichment) and the CD34+ cell yield per 10 litres leukapheresis volume (1 x 106/kg [0.8-2-2]) was much smaller compared with the 10μg/kg group. In conclusion, sufficient amounts of PBPC capable of restoring haemopoiesis in allogeneic recipients can be mobilized safely by administration of G-CSF (10 μg/kg s.c. for 5 d) in healthy donors, and harvested with one or two leukapheresis procedures. Whether the large numbers of T-cells and NK cells that are contained in the collection products may influence graft-versus-host and graft-versus-leukaemia reactivities of PBPC grafts remains to be determined.
British Journal of Haematology 10/2008; 87(3):609 - 613. · 4.94 Impact Factor
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The Lancet Oncology 08/2006; 7(7):605-7. · 22.59 Impact Factor
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ABSTRACT: Familial neuroblastoma is of special interest in view of the oncogenesis of this tumour with its early manifestation in childhood. The inheritance seems to follow an autosomal-dominant mendelian trait with incomplete penetrance. Familial neuroblastomas and ganglioneuromas have not been reported in detail within large treatment studies. A retrospective clinicopathological survey of patients reported to the German neuroblastoma treatment studies over 24 years was performed. Among 2863 patients (2752 neuroblastomas, 111 ganglioneuromas) included in five consecutive trials, only 22 hereditary cases in ten families were observed. Neuroblastomas were found in 18 patients and ganglioneuromas in four, accounting for less than one percent of all cases. Six patients with neuroblastomas had localised disease, seven had stage 4, three had stage 4S, and stage was unknown in two patients. Two families had three affected patients. Contrary to previous reports, age distribution and number of primary tumours in patients with familial data confirm the low prevalence of familial neuroblastoma and may help in counselling the affected families.
European Journal of Cancer 01/2005; 40(18):2760-5. · 5.54 Impact Factor
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ABSTRACT: Despite high-dose chemotherapy and autografting, the outcome for patients with primary refractory Hodgkin's disease (HD) or multiple relapses remains unsatisfactory. Six pediatric patients (median age: 16 years, range: 11-19) received reduced intensity conditioning and allogeneic peripheral blood stem cell transplantation (PBSCT) after failure of stratified first-line chemotherapy, involved-field radiotherapy, and salvage chemotherapy including autologous PBSCT (two patients). For conditioning, fludarabine was combined with busulfan (8 or 12 mg/kg) and additional cyclophosphamide (three patients), or without cyclophosphamide (two patients), or melphalan (one patient). Two patients died of infections and one of progression. One patient remains in complete remission 59 months following transplantation. Two patients relapsed but responded after withdrawal of immunosuppression, chemotherapy, or donor lymphocyte infusions and are alive at 22 and 36 months post transplant, respectively. Allogeneic PBSCT, with reduced intensity conditioning, may be beneficial for selected patients with refractory HD.
Annals of Hematology 05/2004; 83(4):237-41. · 2.62 Impact Factor
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ABSTRACT: Despite high-dose chemotherapy and autografting, the outcome for patients with primary refractory Hodgkins disease (HD) or multiple relapses remains unsatisfactory. Six pediatric patients (median age: 16years, range: 11–19) received reduced intensity conditioning and allogeneic peripheral blood stem cell transplantation (PBSCT) after failure of stratified first-line chemotherapy, involved-field radiotherapy, and salvage chemotherapy including autologous PBSCT (two patients). For conditioning, fludarabine was combined with busulfan (8 or 12mg/kg) and additional cyclophosphamide (three patients), or without cyclophosphamide (two patients), or melphalan (one patient). Two patients died of infections and one of progression. One patient remains in complete remission 59months following transplantation. Two patients relapsed but responded after withdrawal of immunosuppression, chemotherapy, or donor lymphocyte infusions and are alive at 22 and 36months post transplant, respectively. Allogeneic PBSCT, with reduced intensity conditioning, may be beneficial for selected patients with refractory HD.
Annals of Hematology 03/2004; 83(4):237-241. · 2.62 Impact Factor
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Medical and Pediatric Oncology 03/2002; 38(2):125-7.
