Long-Term Outcome in Children With Relapsed ALL by Risk-Stratified Salvage Therapy: Results of Trial Acute Lymphoblastic Leukemia-Relapse Study of the Berlin-Frankfurt-Münster Group 87

Einsiedel, Hagen Graf; Stackelberg, Arend von; Hartmann, Reinhard; Fengler, R.; Schrappe, Martin; Janka‐Schaub, Gritta; Mann, Georg; Hählen, K.; Göbel, U.; Klingebiel, Thomas; Ludwig, Wolf‐Dieter; Henze, Günter

doi:10.1200/jco.2005.01.1031

Cited by 263 publications

(202 citation statements)

References 29 publications

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“…1. This patient had relapsed T-cell ALL that was refractory to four prior salvage regimens, including BerlinFrankfurt-Munich (BFM) R1 and R2, 21 fludarabine/ nelaralbine combination, 22 FLAG/idarubicin 23 with further allo-HSCT rescue, which contained a large number (162 million CD3 þ cells/kg) of T cells, followed by another DLI, but with persistence of 70% marrow blasts. The patient finally achieved a marrow remission after the fifth salvage regimen comprising of gemcitabine and mitoxantrone 24 followed by the first CIK cell infusion.…”

Section: Feasibility Of Cik Cell Expansionmentioning

confidence: 99%

The anti-tumour activity of allogeneic cytokine-induced killer cells in patients who relapse after allogeneic transplant for haematological malignancies

Niam

et al. 2011

Bone Marrow Transplant

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We performed a Phase I/II clinical trial to study the feasibility, toxicity and efficacy of allogeneic cytokineinduced killer (CIK) cell expansion, and treatment for patients with haematological malignancies who relapsed after allogeneic haemopoietic SCT (allo-HSCT). Allogeneic CIK cells were successfully generated for a total of 24 patients, including those from patients' own leukapheresis products in 5 patients who had no access to further donor cells. The median CD3 þ T-cell expansion was 9.33 (1.3-38.97) fold, and CD3 þ CD56 þ natural killer (NK)-like T-cell expansion was 27.77 (2.59-438.93) fold. A total of 55 infusions were done for 16 patients who had either failed or progressed after initial response to various individualized chemotherapy regimens and donor lymphocyte infusion (DLI), at doses ranging from 10 to 200 million CD3 þ cells/kg. Response attributable to CIK cell infusion was observed in five patients. These included two with ALL, two with Hodgkin's disease (HD) and one with AML, and two of whom had a response sustained for more than 2 years. Acute GVHD occurred in three and was easily treatable. This study provides some evidence suggestive of the efficacy of allogeneic CIK cells even after failure of DLI in some cases.

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Section: Feasibility Of Cik Cell Expansionmentioning

confidence: 99%

The anti-tumour activity of allogeneic cytokine-induced killer cells in patients who relapse after allogeneic transplant for haematological malignancies

Niam

et al. 2011

Bone Marrow Transplant

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“…[1][2][3][4][5][6][7][8][9] However, the treatment is still controversial for low-risk relapses, which either involve extramedullary sites only and/or occur late in the BM. [10][11][12][13][14] Autologous transplantation may be an alternative to chemotherapy for ALL in CR2 after low-risk relapse.…”

Section: Introductionmentioning

confidence: 99%

Autologous purified peripheral blood SCT in childhood low-risk relapsed ALL

Balduzzi

Bonanomi

Valsecchi

et al. 2010

Bone Marrow Transplant

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The treatment of childhood B-cell-precursor ALL after isolated-extramedullary or late relapse is controversial. Most approaches are based on chemotherapy or allogeneic transplantation. The aim of this report is to assess the long-term outcome of children with 'low-risk' relapsed ALL treated according to a prospective purified autotransplantation protocol. From January 1997 to March 2004, at a single pediatric Center, 30 ALL consecutive children, lacking an HLA-identical sibling, were treated according to the autologous purified peripheral blood stem cell protocol after isolated-extramedullary (7) or late medullary (24) relapse. After the 'DIAVE' mobilizing regimen a median of 11.6 Â 10 6 CD34 þ /Kg (range 3.9-27.4) were collected. Leukaphereses were depleted by 99% of CD19 þ cells (range 98-100) by means of a double step immunological purification. The conditioning regimen included TBI. No early severe complications nor transplant-related deaths occurred; late effects, as expected, mostly consisted in endocrinological issues and were assessed at a median follow-up of 8.5 years. Five-year-EFS and survival were 68.5% (s.e. 7.9) and 85.7% (s.e. 5.9), respectively, for the 35 eligible patients and 70.0% (s.e. 8.4) and 86.7% (s.e. 6.2) for the 30 patients actually transplanted as per protocol. The outcome of this series favorably compares with historical data regarding both autologous transplantation and standard salvage chemotherapy.

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“…Although event-free survival rates range between 70% and 75%, relapse of ALL remains the fourth most frequent diagnosis in childhood cancer affecting 25% of ALL patients (2). At relapse, overall cure rates of f40% remain unsatisfactory and survival rates are particularly poor in certain subgroups (3). Treatment of relapse usually implies intensified polychemotherapy containing high-dose elements.…”

mentioning

confidence: 99%

Expression of Late Cell Cycle Genes and an Increased Proliferative Capacity Characterize Very Early Relapse of Childhood Acute Lymphoblastic Leukemia

Kirschner-Schwabe

Lottaz

Tödling

et al. 2006

Clinical Cancer Research

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Purpose: In childhood acute lymphoblastic leukemia (ALL), f25% of patients suffer from relapse. In recurrent disease, despite intensified therapy, overall cure rates of 40% remain unsatisfactory and survival rates are particularly poor in certain subgroups. The probability of long-term survival after relapse is predicted from well-established prognostic factors (i.e., time and site of relapse, immunophenotype, and minimal residual disease). However, the underlying biological determinants of these prognostic factors remain poorly understood. Experimental Design: Aiming at identifying molecular pathways associated with these clinically well-defined prognostic factors, we did gene expression profiling on 60 prospectively collected samples of first relapse patients enrolled on the relapse trial ALL-REZ BFM 2002 of the Berlin-Frankfurt-Mu« nster study group. Results: We show here that patients with very early relapse of ALL are characterized by a distinctive gene expression pattern.We identified a set of 83 genes differentially expressed in very early relapsed ALL compared with late relapsed disease. The vast majority of genes were up-regulated and many were late cell cycle genes with a function in mitosis. In addition, samples from patients with very early relapse showed a significant increase in the percentage of S and G 2 -M phase cells and this correlated well with the expression level of cell cycle genes. Conclusions: Very early relapse of ALL is characterized by an increased proliferative capacity of leukemic blasts and up-regulated mitotic genes.The latter suggests that novel drugs, targeting late cell cycle proteins, might be beneficial for these patients that typically face a dismal prognosis.Acute lymphoblastic leukemia (ALL) is the most common malignant disease in children (1). Although event-free survival rates range between 70% and 75%, relapse of ALL remains the fourth most frequent diagnosis in childhood cancer affecting 25% of ALL patients (2). At relapse, overall cure rates of f40% remain unsatisfactory and survival rates are particularly poor in certain subgroups (3). Treatment of relapse usually implies intensified polychemotherapy containing high-dose elements. Although in most children, second remissions can be induced high-risk patients require further treatment intensification by stem cell transplantation. Stem cell transplantation provides a better relapse-free survival rate than chemotherapy alone but is also associated with higher treatment-related morbidity and mortality rates (2). Thus, alternative treatment strategies are needed to improve the treatment and outcome of patients with relapsed ALL.In the treatment of ALL relapse, intensity of chemotherapy and stem cell transplantation are indicated by well-established prognostic factors (summarized in ref.2), with the most evident being the time to relapse. Early recurrence of disease with respect to frontline therapy affects f60% of patients and is associated with a high rate of nonresponse to treatment, shorter duration of second ...

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Long-Term Outcome in Children With Relapsed ALL by Risk-Stratified Salvage Therapy: Results of Trial Acute Lymphoblastic Leukemia-Relapse Study of the Berlin-Frankfurt-Münster Group 87

Cited by 263 publications

References 29 publications

The anti-tumour activity of allogeneic cytokine-induced killer cells in patients who relapse after allogeneic transplant for haematological malignancies

The anti-tumour activity of allogeneic cytokine-induced killer cells in patients who relapse after allogeneic transplant for haematological malignancies

Autologous purified peripheral blood SCT in childhood low-risk relapsed ALL

Expression of Late Cell Cycle Genes and an Increased Proliferative Capacity Characterize Very Early Relapse of Childhood Acute Lymphoblastic Leukemia

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