Haploidentical stem cell transplantation in patients with pediatric solid tumors
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Haploidentical stem cell transplantation in patients with pediatric solid tumors : preliminary results of a pilot study and analysis of graft versus tumor effects. / Lang, P; Pfeiffer, M; Müller, I; Schumm, M; Ebinger, M; Koscielniak, E; Feuchtinger, T; Föll, J; Martin, D; Handgretinger, R.
in: KLIN PADIATR, Jahrgang 218, Nr. 6, 03.11.2006, S. 321-6.Publikationen: SCORING: Beitrag in Fachzeitschrift/Zeitung › SCORING: Zeitschriftenaufsatz › Forschung › Begutachtung
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TY - JOUR
T1 - Haploidentical stem cell transplantation in patients with pediatric solid tumors
T2 - preliminary results of a pilot study and analysis of graft versus tumor effects
AU - Lang, P
AU - Pfeiffer, M
AU - Müller, I
AU - Schumm, M
AU - Ebinger, M
AU - Koscielniak, E
AU - Feuchtinger, T
AU - Föll, J
AU - Martin, D
AU - Handgretinger, R
PY - 2006/11/3
Y1 - 2006/11/3
N2 - Pediatric patients with relapsed metastatic tumors have a poor prognosis and new treatment strategies are warranted. We present preliminary results of a pilot study, evaluating the feasibility and toxicity of transplantation of haploidentical T and B cell depleted grafts with high numbers of NK cells. 6 patients with relapsed metastatic neuroblastomas (n = 4), rhabdomyosarcoma (n = 1) or Ewing's sarcoma (n = 1) after previous autologous transplantation received CD3/CD19 depleted grafts from mismatched family donors with a median number of 16 x 10 (6)/kg stem cells, 167 x 10 (6)/kg Natural Killer cells and only 5.4 x 10 (4)/kg residual T cells. A melphalan-based, reduced intensity conditioning was used. Despite pretransplant chemotherapy, patients entered transplantation with significant tumor burden. Primary engraftment occurred in 6/6 patients. One patient had secondary graft failure. Hematopoietic recovery was rapid (ANC > 0.5 x 10 (9)/L: 11 days (9-12); independence from platelet substitution: 8 days (7-11)). Four patients had acute GvHD grade II, limited chronic GvHD was observed in 2 patients. No transplant-related mortality and only low toxicity occurred. Four patients died from progression, two patients are alive. Overall median survival time is 6 months (2-11) to date. Analysis of posttransplant NK cell function revealed stable cytotoxic activity against K562 targets, whereas activity against neuroblastoma targets was low. Stimulation with cytokines and use of appropriate antibodies clearly enhanced specific lysis in vitro. In summary, these preliminary results indicate the feasibility and low toxicity even in intensively pre-treated patients with neuroblastomas/sarcomas. This approach may form the basis for posttransplant immunomodulation and other therapeutic strategies. Further experience is warranted to evaluate the method.
AB - Pediatric patients with relapsed metastatic tumors have a poor prognosis and new treatment strategies are warranted. We present preliminary results of a pilot study, evaluating the feasibility and toxicity of transplantation of haploidentical T and B cell depleted grafts with high numbers of NK cells. 6 patients with relapsed metastatic neuroblastomas (n = 4), rhabdomyosarcoma (n = 1) or Ewing's sarcoma (n = 1) after previous autologous transplantation received CD3/CD19 depleted grafts from mismatched family donors with a median number of 16 x 10 (6)/kg stem cells, 167 x 10 (6)/kg Natural Killer cells and only 5.4 x 10 (4)/kg residual T cells. A melphalan-based, reduced intensity conditioning was used. Despite pretransplant chemotherapy, patients entered transplantation with significant tumor burden. Primary engraftment occurred in 6/6 patients. One patient had secondary graft failure. Hematopoietic recovery was rapid (ANC > 0.5 x 10 (9)/L: 11 days (9-12); independence from platelet substitution: 8 days (7-11)). Four patients had acute GvHD grade II, limited chronic GvHD was observed in 2 patients. No transplant-related mortality and only low toxicity occurred. Four patients died from progression, two patients are alive. Overall median survival time is 6 months (2-11) to date. Analysis of posttransplant NK cell function revealed stable cytotoxic activity against K562 targets, whereas activity against neuroblastoma targets was low. Stimulation with cytokines and use of appropriate antibodies clearly enhanced specific lysis in vitro. In summary, these preliminary results indicate the feasibility and low toxicity even in intensively pre-treated patients with neuroblastomas/sarcomas. This approach may form the basis for posttransplant immunomodulation and other therapeutic strategies. Further experience is warranted to evaluate the method.
KW - Acute Disease
KW - Adolescent
KW - Adult
KW - Child
KW - Child, Preschool
KW - Cytotoxicity Tests, Immunologic
KW - Disease Progression
KW - Feasibility Studies
KW - Follow-Up Studies
KW - Graft vs Tumor Effect
KW - Haploidy
KW - Humans
KW - Killer Cells, Natural
KW - Neuroblastoma
KW - Peripheral Blood Stem Cell Transplantation
KW - Pilot Projects
KW - Rhabdomyosarcoma
KW - Sarcoma, Ewing
KW - Time Factors
KW - Transplantation Conditioning
KW - Transplantation, Homologous
KW - Treatment Outcome
U2 - 10.1055/s-2006-942256
DO - 10.1055/s-2006-942256
M3 - SCORING: Journal article
C2 - 17080334
VL - 218
SP - 321
EP - 326
JO - KLIN PADIATR
JF - KLIN PADIATR
SN - 0300-8630
IS - 6
ER -
