| 1. |
- Dantonello, Tobias M, et al.
(författare)
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Tumour volume reduction after neoadjuvant chemotherapy impacts outcome in localised embryonal rhabdomyosarcoma
- 2015
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Ingår i: Pediatric Blood & Cancer. - : Wiley. - 1545-5009 .- 1545-5017. ; 62:1, s. 16-23
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Response (tumour volume reduction) to induction chemotherapy has been used to stratify secondary local and systemic treatment of Intergroup Rhabdomyosarcoma Study Group III (IRSG-III) embryonal rhabdomyosarcoma (RME) in consecutive CWS-trials. To evaluate its actual impact we studied response-related treatment and outcomes.PROCEDURE: Patients with IRSG-III RME <21 years and non-response (NR, <33% volume reduction) in five consecutive CWS-trials were analysed and compared with partial responders (PAR, ≥33% reduction). The NR was reviewed and sub-classified as Objective Response (OR, <0%-33% reduction) or Stable/Progressive Disease (SPD).RESULTS: Fifty-nine of 529 patients had NR (n = 34 OR, n = 25 SPD). Primary risk-factors including age, tumour size, and TN-classification did not differ between NR and PAR groups but NR had more patients with unfavourable sites comparatively (P = 0.04). There were no differences in primary risk-factors between OR and SPD. Significant factors associated with poor outcome in multivariate analysis were NR, TN-classification, age >10 years, tumour size >5 cm and therapy in older trials. After response assessment n = 24 NR continued to receive induction chemotherapy, n = 32 received other combinations and n = 3 no further chemotherapy. Forty-two non-responders were irradiated, and the tumours were completely resected in n = 20. After a median follow-up of 8 years, 34 NR are alive. Seventeen of 21 failures leading to disease-related deaths were locoregional. The five-year overall survival rate (OS) was 76 ± 4% for PAR, 79 ± 14% for OR, but only 40 ± 19% for SPD (P < 0.001).CONCLUSION: Response to induction chemotherapy appears to be an important surrogate marker of poor outcome in patients with SPD largely due to ineffective local control.
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| 2. |
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| 3. |
- Illhardt, Toni, et al.
(författare)
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Haploidentical Stem Cell Transplantation for Refractory/Relapsed Neuroblastoma
- 2018
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Ingår i: Biology of Blood and Marrow Transplantation. - : Elsevier BV. - 1083-8791. ; 24:5, s. 1005-1012
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Tidskriftsartikel (refereegranskat)abstract
- Pediatric patients with refractory or relapsed metastatic neuroblastoma (NBL) have a poor prognosis despite autologous stem cell transplantation (SCT). Allogeneic SCT from a haploidentical donor has a remarkable alloreactive effect in patients with leukemia; thus, we evaluated this approach in children with very high-risk NBL. We analyzed data from 2 prospective phase I/II trials. A total of 26 patients with refractory (n = 5), metastatic relapsed (n = 20), or locally relapsed MYCN-positive (n = 1) NBL received a median of 17 × 106/kg T/B cell-depleted CD34+ stem cells with 68 × 103/kg residual T cells and 107 × 106/kg natural killer cells. The conditioning regimen comprised melphalan, fludarabine, thiotepa, OKT3, and a short course of mycophenolate mofetil post-transplantation. Engraftment occurred in 96% of the patients. Event-free survival and overall survival at 5 years were 19% and 23%, respectively. No transplantation-related mortality was observed, and the single death was due to progression/subsequent relapse. The median duration of follow-up was 8.1 years. Patients in complete remission before SCT had a significantly better prognosis than those with residual tumor load (P < .01). All patients with progressive disease before SCT relapsed within 1 year. Grade II and grade III acute graft-versus-host disease (GVHD) occurred in 31% and 12% of the patients, respectively. Chronic limited and extensive GVHD occurred in 28% and 10%, respectively. Our data indicate that haploidentical SCT is a feasible treatment option that can induce long-term remission in some patients with NBL with tolerable side effects, and may enable the development of further post-transplantation therapeutic strategies based on the donor-derived immune system.
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| 4. |
- Koscielniak, Ewa, et al.
(författare)
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Long-Term Clinical Outcome and Prognostic Factors of Children and Adolescents with Localized Rhabdomyosarcoma Treated on the CWS-2002P Protocol
- 2022
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Ingår i: Cancers. - : MDPI AG. - 2072-6694. ; 14:4
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Tidskriftsartikel (refereegranskat)abstract
- Simple SummaryThe major challenge in pediatric oncology is the optimal adaptation of therapy burden to risk profile, aiming to achieve the best outcome with minimum toxicities. The CWS-2002P study in patients <= 21 years with localized rhabdomyosarcoma was developed with this goal by reducing or intensifying the chemotherapy depending on the risk group. An important additional aim was to investigate the use of low-dose maintenance chemotherapy. The risk stratification system was effective in predicting outcomes in the four risk groups with very good long-term results. Neither the reduction nor the intensification of chemotherapy influenced the outcome in comparison to previous studies showing that further de-escalation of chemotherapy should be investigated. The weighting of risk factors used for therapy stratification needs to be reevaluated. Maintenance therapy seemed to have an impact on prognosis.We report here the results of the prospective, non-randomized, historically controlled CWS-2002P study in patients <= 21 years with localized RMS developed with the aim to improve the long-term outcome by adapting the burden of therapy to risk profile and to investigate the feasibility and relation to the outcome of maintenance therapy (MT) in the high-risk groups. Patients were allocated into low-risk (LR), standard-risk (SR), high-risk (HR), and very high-risk (VHR) groups. Chemotherapy consisted of vincristine (VCR) and dactinomycin (ACTO-D) for all patients with the addition of ifosfamide (IFO) in the SR, HR, and VHR and doxorubicin (DOX) in the HR and VHR groups. Low-dose cyclophosphamide and vinblastine maintenance therapy (MT) over 6 months was recommended in the HR and VHR groups. A total of 444 patients have been included in this analysis. With a median follow-up of 9 center dot 6 years (IQR 7 center dot 6-10 center dot 9) for patients alive, the 5-year EFS and OS for the whole group was 73% (95% CI 69-77) and 80% (95% CI 76-84), respectively. The 5-year EFS by risk group was 100% in the LR, 79% (95% CI 72-84) in the SR, 69% (95% CI 63-75) in the HR, and 42% (95% CI 23-61) in the VHR (log-rank p = 0.000). The 5-year EFS was 77% (95% CI 70-84) for 155 patients in the HR group who received MT as compared to 63% (95% CI 50-76) for 49 patients who did not (log-rank p = 0.015). Neither the reduction in the IFO dose in the SR nor the increased dose intensity of DOX in HR groups influenced the outcome when compared to the previous CWS and other European studies. MT was feasible, seemed to have an impact on prognosis, and should be studied in a well-controlled prospective trial in this patient population. The weighting of risk factors used for therapy stratification needs to be reevaluated.
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| 5. |
- Oevermann, Lena, et al.
(författare)
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KIR B haplotype donors confer a reduced risk of relapse after haploidentical transplantation in children with acute lymphoblastic leukemia.
- 2014
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Ingår i: Blood. - : American Society of Hematology. - 1528-0020 .- 0006-4971. ; 124:17, s. 2744-2747
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Tidskriftsartikel (refereegranskat)abstract
- We analyzed the influence of donor killer-cell immunoglobulin-like receptor (KIR) gene haplotypes on the risk of relapse and probability of event-free survival (EFS) in children with acute lymphoblastic leukemia (ALL) who received HLA-haploidentical transplantation of ex vivo T-cell depleted peripheral blood stem cells. The KIR gene haplotype was evaluated in 85 donors and the KIR B-content score was determined in the 63 KIR haplotype-B donors. Patients transplanted from a KIR haplotype-B donor had a significantly better EFS than those transplanted from a KIR A-donor (50.6% versus 29.5%, respectively, p=0.033). Moreover, a high donor KIR B-content score was associated with a significantly reduced risk of relapse (Log-rank test for trend p=0.026). These data indicate that KIR genotyping should be included in the donor selection algorithm for haploidentical transplantation in children with ALL with the aim of choosing, whenever possible, a KIR haplotype-B donor with a high KIR B-content score.
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