Treatment of High-Risk Neuroblastoma With Triple-Tandem High-Dose Therapy and Stem-Cell Rescue: Results of the Chicago Pilot II Study

2002 ◽  
Vol 20 (9) ◽  
pp. 2284-2292 ◽  
Author(s):  
Morris Kletzel ◽  
Howard M. Katzenstein ◽  
Paul R. Haut ◽  
Alice L. Yu ◽  
Elaine Morgan ◽  
...  
Keyword(s):  
Stem Cell ◽  
High Risk ◽  
Induction Therapy ◽  
Peripheral Blood ◽  
Peripheral Blood Stem Cell ◽  
Blood Stem Cell ◽  
High Dose ◽  
High Dose Therapy ◽  
Dose Therapy ◽  
Stem Cell Rescue

PURPOSE: To investigate whether intensive induction therapy followed by triple-tandem cycles of high-dose therapy with peripheral-blood stem-cell rescue and local irradiation will improve event-free survival for patients with high-risk neuroblastoma. PATIENTS AND METHODS: From August 1995 to January 2000, 25 consecutive newly diagnosed high-risk neuroblastoma patients and one child with recurrent MYCN-amplified disease were enrolled onto the Chicago Pilot II Protocol. After induction therapy and surgery, peripheral-blood stem cells were mobilized with three cycles of high-dose cyclophosphamide and granulocyte colony-stimulating factor. Patients then underwent triple-tandem cycles of high-dose therapy with peripheral-blood stem-cell rescue followed by radiation to the primary site. RESULTS: Twenty-two of the 26 patients successfully completed induction therapy and were eligible for the triple-tandem consolidation high-dose therapy. Sufficient numbers of peripheral-blood stem cells were collected in all but one patient. Seventeen patients were able to complete all three cycles of high-dose therapy and peripheral-blood stem-cell rescue, two patients completed two cycles, and three patients completed one cycle. There was one toxic death, and one patient died from complications of treatment for graft failure. With a median follow-up of 38 months, the 3-year event-free survival and survival rates are 57% ± 11% and 79% ± 10%, respectively. CONCLUSION: The results of this pilot study demonstrate that it is feasible to intensify consolidation with triple-tandem high-dose chemotherapy and peripheral-blood stem-cell rescue and local irradiation, and suggest that this treatment strategy may lead to improved survival for patients with high-risk neuroblastoma.

High-Dose Therapy and Autologous Peripheral Blood Stem Cell Transplantation in Multiple Myeloma: Up-front or Rescue Treatment? Results of a Multicenter Sequential Randomized Clinical Trial

Blood ◽  
1998 ◽  
Vol 92 (9) ◽  
pp. 3131-3136 ◽  
Author(s):  
Jean-Paul Fermand ◽  
Philippe Ravaud ◽  
Sylvie Chevret ◽  
Marine Divine ◽  
Véronique Leblond ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Stem Cell ◽  
Peripheral Blood ◽  
Peripheral Blood Stem Cell ◽  
Blood Stem Cell ◽  
High Dose ◽  
High Dose Therapy ◽  
Dose Therapy ◽  
Rescue Treatment ◽  
Late Group

Results to date indicate that high-dose therapy (HDT) with autologous stem cell support improves survival of patients with symptomatic multiple myeloma (MM). We performed a multicenter, sequential, randomized trial designed to assess the optimal timing of HDT and autotransplantation. Among 202 enrolled patients who were up to 56 years old, 185 were randomly assigned to receive HDT and peripheral blood stem cell (PBSC) autotransplantation (early HDT group, n = 91) or a conventional-dose chemotherapy (CCT) regimen (late HDT group, n = 94). In the late HDT group, HDT and transplantation were performed as rescue treament, in case of primary resistance to CCT or at relapse in responders. PBSC were collected before randomization, after mobilization by chemotherapy, and, in the two groups, HDT was preceded by three or four treatments with vincristine, doxorubicin, and methylprednisolone. Data were analyzed on an intent-to-treat basis using a sequential design. Within a median follow-up of 58 months, estimated median overall survival (OS) was 64.6 months in the early HDT group and 64 months in the late group. Survival curves were not different (P = .92, log-rank test). Median event-free survival (EFS) was 39 months in the early HDT group whereas median time between randomization and CCT failure was 13 months in the late group. Average time without symptoms, treatment, and treatment toxicity (TWiSTT) were 27.8 months (95% confidence interval [CI]; range, 23.8 to 31.8) and 22.3 months (range, 16.0 to 28.6) in the two groups, respectively. HDT with PBSC transplantation obtained a median OS exceeding 5 years in young patients with symptomatic MM, whether performed early, as first-line therapy, or late, as rescue treatment. Early HDT may be preferred because it is associated with a shorter period of chemotherapy. © 1998 by The American Society of Hematology.

High-Dose Therapy and Autologous Peripheral Blood Stem Cell Transplantation in Multiple Myeloma: Up-front or Rescue Treatment? Results of a Multicenter Sequential Randomized Clinical Trial

Blood ◽  
1998 ◽  
Vol 92 (9) ◽  
pp. 3131-3136 ◽  
Author(s):  
Jean-Paul Fermand ◽  
Philippe Ravaud ◽  
Sylvie Chevret ◽  
Marine Divine ◽  
Véronique Leblond ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Stem Cell ◽  
Peripheral Blood ◽  
Peripheral Blood Stem Cell ◽  
Blood Stem Cell ◽  
High Dose ◽  
High Dose Therapy ◽  
Dose Therapy ◽  
Rescue Treatment ◽  
Late Group

Abstract Results to date indicate that high-dose therapy (HDT) with autologous stem cell support improves survival of patients with symptomatic multiple myeloma (MM). We performed a multicenter, sequential, randomized trial designed to assess the optimal timing of HDT and autotransplantation. Among 202 enrolled patients who were up to 56 years old, 185 were randomly assigned to receive HDT and peripheral blood stem cell (PBSC) autotransplantation (early HDT group, n = 91) or a conventional-dose chemotherapy (CCT) regimen (late HDT group, n = 94). In the late HDT group, HDT and transplantation were performed as rescue treament, in case of primary resistance to CCT or at relapse in responders. PBSC were collected before randomization, after mobilization by chemotherapy, and, in the two groups, HDT was preceded by three or four treatments with vincristine, doxorubicin, and methylprednisolone. Data were analyzed on an intent-to-treat basis using a sequential design. Within a median follow-up of 58 months, estimated median overall survival (OS) was 64.6 months in the early HDT group and 64 months in the late group. Survival curves were not different (P = .92, log-rank test). Median event-free survival (EFS) was 39 months in the early HDT group whereas median time between randomization and CCT failure was 13 months in the late group. Average time without symptoms, treatment, and treatment toxicity (TWiSTT) were 27.8 months (95% confidence interval [CI]; range, 23.8 to 31.8) and 22.3 months (range, 16.0 to 28.6) in the two groups, respectively. HDT with PBSC transplantation obtained a median OS exceeding 5 years in young patients with symptomatic MM, whether performed early, as first-line therapy, or late, as rescue treatment. Early HDT may be preferred because it is associated with a shorter period of chemotherapy. © 1998 by The American Society of Hematology.

Increased Incidence of Cytomegalovirus Disease After Autologous CD34-Selected Peripheral Blood Stem Cell Transplantation

Blood ◽  
1999 ◽  
Vol 94 (12) ◽  
pp. 4029-4035 ◽  
Author(s):  
Leona A. Holmberg ◽  
Michael Boeckh ◽  
Heather Hooper ◽  
Wendy Leisenring ◽  
Scott Rowley ◽  
...  
Keyword(s):  
Stem Cell ◽  
Peripheral Blood ◽  
Peripheral Blood Stem Cell ◽  
Multivariate Logistic Regression Analysis ◽  
Blood Stem Cell ◽  
High Dose ◽  
High Dose Therapy ◽  
Dose Therapy ◽  
Cmv Disease ◽  
Cd34 Selection

Abstract High-dose therapy with autologous peripheral blood stem cell (PBSC) rescue is widely used for the treatment of malignant disease. CD34 selection of PBSC has been applied as a means of reducing contamination of the graft. Although CD34 selection results in a 2 to 3 log reduction in contaminating tumor cells without significantly delaying engraftment, many other types of cells are depleted from the CD34-enriched grafts and immune reconstitution may be impaired. In the present study, 31 cytomegalovirus (CMV)-seropositive patients who received myeloablative therapy followed by the infusion of CD34-selected autologous PBSC were assessed for the development of CMV disease in the first 100 days posttransplant. Seven patients (22.6%) developed CMV disease and 4 patients (12.9%) died from complications of their infection. In a contemporaneous group of 237 CMV-seropositive patients receiving unselected, autologous PBSC, only 10 patients (4.2%) developed CMV disease, with 5 deaths (2.1%). In a multivariate logistic regression analysis, the use of CD34-selected autologous PBSC after high-dose therapy was associated with a marked increase in the incidence of CMV disease and CMV-associated deaths.

Increased Incidence of Cytomegalovirus Disease After Autologous CD34-Selected Peripheral Blood Stem Cell Transplantation

Blood ◽  
1999 ◽  
Vol 94 (12) ◽  
pp. 4029-4035 ◽  
Author(s):  
Leona A. Holmberg ◽  
Michael Boeckh ◽  
Heather Hooper ◽  
Wendy Leisenring ◽  
Scott Rowley ◽  
...  
Keyword(s):  
Stem Cell ◽  
Peripheral Blood ◽  
Peripheral Blood Stem Cell ◽  
Multivariate Logistic Regression Analysis ◽  
Blood Stem Cell ◽  
High Dose ◽  
High Dose Therapy ◽  
Dose Therapy ◽  
Cmv Disease ◽  
Cd34 Selection

High-dose therapy with autologous peripheral blood stem cell (PBSC) rescue is widely used for the treatment of malignant disease. CD34 selection of PBSC has been applied as a means of reducing contamination of the graft. Although CD34 selection results in a 2 to 3 log reduction in contaminating tumor cells without significantly delaying engraftment, many other types of cells are depleted from the CD34-enriched grafts and immune reconstitution may be impaired. In the present study, 31 cytomegalovirus (CMV)-seropositive patients who received myeloablative therapy followed by the infusion of CD34-selected autologous PBSC were assessed for the development of CMV disease in the first 100 days posttransplant. Seven patients (22.6%) developed CMV disease and 4 patients (12.9%) died from complications of their infection. In a contemporaneous group of 237 CMV-seropositive patients receiving unselected, autologous PBSC, only 10 patients (4.2%) developed CMV disease, with 5 deaths (2.1%). In a multivariate logistic regression analysis, the use of CD34-selected autologous PBSC after high-dose therapy was associated with a marked increase in the incidence of CMV disease and CMV-associated deaths.

Scintigraphic Response by 123I-Metaiodobenzylguanidine Scan Correlates With Event-Free Survival in High-Risk Neuroblastoma

2004 ◽  
Vol 22 (19) ◽  
pp. 3909-3915 ◽  
Author(s):  
Howard M. Katzenstein ◽  
Susan L. Cohn ◽  
Richard M. Shore ◽  
Dianna M.E. Bardo ◽  
Paul R. Haut ◽  
...  
Keyword(s):  
Stem Cell ◽  
High Risk ◽  
Induction Therapy ◽  
Peripheral Blood Stem Cell ◽  
High Dose ◽  
Event Free Survival ◽  
High Dose Therapy ◽  
Free Survival ◽  
Stem Cell Rescue ◽  
Bone Scans

Purpose To investigate whether response to induction therapy, evaluated by metaiodobenzylguanadine (MIBG) and bone scintigraphy, correlates with event-free survival (EFS) in children with high-risk neuroblastoma (NB). Patients and Methods Twenty-nine high-risk NB patients were treated prospectively with an intensive induction regimen and consolidated with three cycles of high-dose therapy with peripheral blood stem-cell rescue. The scintigraphic response was evaluated by MIBG and bone scans using a semi-quantitative scoring system. The prognostic significance of the imaging scores at diagnosis and following induction therapy was evaluated. Results A trend associating worse 4-year EFS rates for patients with versus without osteomedullary uptake on MIBG scintigraphs at diagnosis was seen (35% ± 11% v 80% ± 18%, respectively; P = .13). Similarly, patients with positive bone scans at diagnosis had worse EFS than those with negative scans, although the difference did not receive statistical significance (34% ± 10% v 83% ± 15%, respectively; P = .06). However, significantly worse EFS was observed in patients with a postinduction MIBG score of ≥ 3 compared to those with scores of less than 3 (0% v 58% ± 11%; P = .002). There was no correlation between bone scan scores and outcome following induction therapy. Conclusion MIBG scores ≥ 3 following induction therapy identifies a subset of NB patients who are likely to relapse following three cycles of high-dose therapy with peripheral blood stem-cell rescue, local radiotherapy, and 13-cis-retinoic acid. Alternative therapeutic strategies should be considered for patients with a poor response to induction therapy.

High-Risk Neuroblastoma Treated With Tandem Autologous Peripheral-Blood Stem Cell–Supported Transplantation: Long-Term Survival Update

2006 ◽  
Vol 24 (18) ◽  
pp. 2891-2896 ◽  
Author(s):  
Rani E. George ◽  
Shuli Li ◽  
Cheryl Medeiros-Nancarrow ◽  
Donna Neuberg ◽  
Karen Marcus ◽  
...  
Keyword(s):  
Stem Cell ◽  
High Risk ◽  
Peripheral Blood ◽  
Peripheral Blood Stem Cell ◽  
Blood Stem Cell ◽  
Term Survival ◽  
Long Term Survival ◽  
Stem Cell Rescue ◽  
Cns Relapse

Purpose To provide an update on long-term survival of patients with high-risk neuroblastoma treated with tandem cycles of myeloablative therapy and peripheral-blood stem-cell rescue (PBSCR). Patients and Methods Ninety-seven patients with high-risk neuroblastoma were treated between 1994 and 2002. Patients underwent induction therapy with five cycles of standard agents, resection of the primary tumor and local radiation, and two consecutive courses of myeloablative therapy (including total-body irradiation) with PBSCR. Results Fifty-one patients have experienced relapse or died. Median follow-up time among the 46 patients who remain alive without progression is 5.6 years (range, 15.1 months to 9.9 years). Progression-free survival (PFS) rate at 5 years from diagnosis was 47% (95% CI, 36% to 56%), and PFS rate at 7 years was 45% (95% CI, 34% to 55%). Overall survival rate was 60% (95% CI, 48% to 69%) and 53% (95% CI, 40% to 64%) at 5 and 7 years, respectively. The 5- and 7- year PFS rates from time of first transplantation for 82 patients who completed both transplants were 54% (95% CI, 42% to 64%) and 52% (95% CI, 40% to 63%), respectively. Five patients died from treatment-related toxicity after tandem transplantation. Relapse occurred in 37 (42%) of 89 patients, mainly within 3 years of transplantation and primarily in diffuse osseous sites. No primary CNS relapse or secondary leukemia was seen. One patient developed synovial cell sarcoma 8 years after therapy. Conclusion High-dose therapy with tandem autologous stem-cell rescue is effective for treating high-risk neuroblastoma, with encouraging long-term survival. CNS relapse and secondary malignancies are rare after this therapy.

Sign in / Sign up

Export Citation Format

Share Document