Bone Marrow Transplantation for Philadelphia Chromosome Positive Acute Lymphoblastic Leukemia

Stockshläder, M; Hegewisch-Becker, S.; Krüger, William; Dieck, A T; Hoffknecht, M.; Cl, Berger; Kohlschütter, Brigitte; Martin, Hans; Peters, Sönke; Kabisch, H; Kuse, R.; Weh, H. J.; Hossfeld, D. K.; Zander, Axel R.

doi:10.1007/978-3-642-60377-8_107

Cited by 40 publications

(45 citation statements)

References 27 publications

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“…There does appear to be a survival advantage over chemotherapy using matched-sibling HSCT in this group of patients but this is solely based on single arm studies with 3-year LFS rates of 45-84%. [13][14][15] High-risk features generally used to identify patients for HSCT in CR1 are age less than 1 year at diagnosis, poor risk cytogenetic findings, and poor response to induction. [16][17][18] The main differences pretransplant between the two groups relate to the graft characteristics.…”

Section: Discussionmentioning

confidence: 99%

Outcomes of unrelated cord blood transplants and allogeneic-related hematopoietic stem cell transplants in children with high-risk acute lymphocytic leukemia

Jacobsohn

Hewlett

Ranalli

et al. 2004

Bone Marrow Transplant

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Summary:Acute lymphocytic leukemia (ALL) is a common indication for hematopoietic stem cell transplantation (HSCT) in children. Use of unrelated cord blood (UCB) has become increasingly popular as a stem cell source, given the rapid availability and decreased GVHD potential. Publications describing outcomes of children with leukemia who underwent UCB transplants have compared them to those having received unrelated donor marrow transplants. Results are similar. We compared our outcomes using UCB vs allogeneic-related hematopoietic stem cells in pediatric ALL patients since 1992. A total of 49 patients were analyzed. All patients were either in CR1 with high-risk features (n ¼ 21) or in CR2 (n ¼ 28) with initial remission less than 36 months. Patients received myeloablation with fractionated total body irradiation, cyclophosphamide, and etoposide and GVHD prophylaxis with cyclosporine and methotrexate. Antithymocyte globulin was added for UCB recipients to address the HLA differences. In all, 23 patients underwent allogeneic -related HSCT and 26 underwent UCB transplantation. Other than increased time to engraftment for UCB recipients, results are equivalent. The 3-year overall survival is 64% and 3-year event-free survival is 60% for both groups. Rates of GVHD and transplant-related mortality are also equivalent. UCB is a reasonable option for children with ALL who are referred for HSCT. Although the majority of children with acute lymphocytic leukemia (ALL) enjoy excellent outcomes with conventional multiagent chemotherapy, the outlook for those patients who develop recurrent disease, particularly within the first 2 years of therapy, is far less favorable. Patients who relapse within 24 months of diagnosis and are treated with chemotherapy alone have less than 20% survival. 1,2 Hematopoietic stem cell transplantation (HSCT) has been commonly employed for patients with relapse or high-risk features. 3,4 While most children with recurrent or high-risk ALL can achieve a remission with intensified therapy, the most appropriate management strategy to employ once remission has been achieved remains controversial. Some transplant centers base that decision on whether a matched related donor is available.For patients with relapse, HSCT with HLA-matched related donors during the second complete remission (CR2) has provided leukemia-free survival (LFS) rates in the range of 40-50% at 2-5 years. 3,4 There exists controversy with regard to what length of time defines a late relapse after which point an HSCT may have no advantage over chemotherapy. In analyzing 287 patients with ALL in CR2, Uderzo reported no advantage of matched-sibling HSCT over chemotherapy for patients who relapsed more than 30 months from diagnosis. 5 With unrelated cord blood transplantation (UCBT) for ALL and AML, a relapse on therapy prior to transplant confers a worse LFS (22% on therapy vs 48% off therapy). 6 UCB can be an attractive alternative stem cell source for a variety of reasons. Cells are rapidly available, HLAmatching can be considerably...

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Section: Discussionmentioning

confidence: 99%

Outcomes of unrelated cord blood transplants and allogeneic-related hematopoietic stem cell transplants in children with high-risk acute lymphocytic leukemia

Jacobsohn

Hewlett

Ranalli

et al. 2004

Bone Marrow Transplant

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“…8,12,18 The overall experience of allogeneic BMT shows a disease-free survival of 20-75%, with a relapse rate ranging from 11 to 63%. [10][11][12][13][14][15] These reports include patients in various stages of remission who received autologous stem cells, or allogeneic stem cells from MRD or unrelated donors. Late relapses were seen in all the studies, independent of the type of transplant.…”

Section: Discussionmentioning

confidence: 99%

“…[2][3][4]6 Myeloablative chemotherapy followed by haematopoietic stem-cell rescue from an allogeneic donor in CR1 has been shown to cure 20-75% of patients. [7][8][9][10][11][12][13][14][15][16][17][18] Hence, allogeneic bone marrow transplant (BMT) from MRD and MUD has been used as post-induction therapy to improve DFS for patients with Ph þ ALL. [7][8][9][10][11][12][13][14][15][16][17][18] Pediatric experience with this disease has suggested that Ph þ ALL is more heterogeneous with respect to treatment responsiveness than previously suspected.…”

Section: Allogeneic Bone Marrow Transplantationmentioning

confidence: 99%

“…[7][8][9][10][11][12][13][14][15][16][17][18] Hence, allogeneic bone marrow transplant (BMT) from MRD and MUD has been used as post-induction therapy to improve DFS for patients with Ph þ ALL. [7][8][9][10][11][12][13][14][15][16][17][18] Pediatric experience with this disease has suggested that Ph þ ALL is more heterogeneous with respect to treatment responsiveness than previously suspected. [19][20][21] Clinical parameters like WBC count at diagnosis, 19,20 good initial steroid response 21 and age of the patient at diagnosis 20 were shown to be predictive of treatment responsiveness and durable remissions.…”

Section: Allogeneic Bone Marrow Transplantationmentioning

confidence: 99%

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Allogeneic bone marrow transplantation vs chemotherapy for children with Philadelphia chromosome-positive acute lymphoblastic leukemia

Sharathkumar

Saunders

Dror

et al. 2003

Bone Marrow Transplant

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Summary:Allogeneic bone marrow transplant (BMT) with an MRD in complete remission (CR)1 is the preferred treatment for children with Philadelphia-positive (Ph þ ) ALL. The role of MUD BMT in CR1 is still controversial. We compared the outcomes of two treatment strategies: BMT using an MRD or MUD vs chemotherapy in children with Ph þ ALL in CR1. In total, 21 children were treated from 1985 to 2001. In all, 10 received chemotherapy and 11 received allogeneic BMT: four MRD, seven MUD. In the MRD group, one relapsed 12 months after BMT and died; the remaining three are long-term event-free survivors (median follow-up, 6.1 years). In the MUD group four died; the remaining three are long-term event-free survivors (median follow-up, 7.2 years). The 4-year event-free survival (EFS) for the BMT group was 53715%. In the chemotherapy group, seven relapsed after a median period of 12.5 months and three remain in continuous CR (median follow-up, 2.4 years). Four chemotherapy patients received CR2 transplants; all died. The 4-year EFS for the chemotherapy and MUD groups was 33717 and 35.7720%, respectively. This difference was not statistically significant. We continue to support treating children with Ph þ ALL with MRD BMT in CR1. The effectiveness of MUD BMT vs chemotherapy merits further study.

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“…Allogeneic bone marrow transplantation (BMT) is an effective consolidation treatment for patients in complete remission from acute leukaemia or lymphoblastic lymphoma (Chao et al, 1991;De Witte et al, 1994;Jourdan et al, 1995;Ringden et al, 1987;Stockschläder et al, 1995;Zittoun et al, 1995). In chronic myeloid leukaemia, myelodysplastic syndrome and low-grade non-Hodgkin's lymphoma, BMT is the only curative treatment (Anderson et al, 1995;Clift et al, 1993;De Witte & Gratwohl, 1993;Goldman et al, 1988;Gratwohl et al, 1993;Lazarus, 1995).…”

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confidence: 99%

Outcome of transplantation for standard‐risk leukaemia with grafts depleted of lymphocytes after conditioning with an intensified regimen

Schaap¹,

Schattenberg²,

Bär³

et al. 1997

Br J Haematol

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Summary.One hundred and eighty-one consecutive patients with standard-risk leukaemia were transplanted with HLAidentical sibling grafts depleted of lymphocytes using counterflow centrifugation. In 116 patients, standard conditioning was intensified by the addition of anthracyclines.Multivariate analysis revealed significantly more acute GVHD 5 grade 2 and a trend towards more chronic GVHD in patients conditioned with the addition of anthracyclines. For all patients the risk for chronic GVHD, but not for acute GVHD, increased with a higher number of T cells in the graft. The projected 5-year probability of relapse was significantly lower in the group of patients conditioned with anthracyclines; 26% versus 52% (P ¼ 0 . 015). In multivariate analysis the addition of anthracyclines to the conditioning regimen was the only significant factor contributing to a lower probability of relapse. The projected 5-year probability of leukaemia-free survival [LFS] in the patients conditioned with and without the addition of anthracyclines was 56% and 36%, respectively (P ¼ 0 . 004). In multivariate analysis the addition of anthracyclines to the conditioning regimen correlated significantly with a lower number of mixed chimaeras in patients at 6 and 12 months after BMT. Mixed chimaerism at 6 months after transplantation did not significantly correlate with a higher incidence of relapse in further follow-up. In contrast, mixed chimaerism at 12 months after BMT was significantly associated with higher relapse rate.We conclude that the addition of anthracyclines to the conditioning regimen improves outcome of BMT using Tcell-depleted grafts.

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Bone Marrow Transplantation for Philadelphia Chromosome Positive Acute Lymphoblastic Leukemia

Cited by 40 publications

References 27 publications

Outcomes of unrelated cord blood transplants and allogeneic-related hematopoietic stem cell transplants in children with high-risk acute lymphocytic leukemia

Outcomes of unrelated cord blood transplants and allogeneic-related hematopoietic stem cell transplants in children with high-risk acute lymphocytic leukemia

Allogeneic bone marrow transplantation vs chemotherapy for children with Philadelphia chromosome-positive acute lymphoblastic leukemia

Outcome of transplantation for standard‐risk leukaemia with grafts depleted of lymphocytes after conditioning with an intensified regimen

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