Double-alkylator non-total-body irradiation regimen with autologous hematopoietic stem-cell transplantation in pediatric solid tumors.

Özkaynak, M. Fevzi; Matthay, K. K.; Cairo, Mitchell S.; Harris, Richard E.; Feig, Stephen A.; Reynolds, C. Patrick; Buckley, John D.; Villablanca, J. G.; Seeger, Robert C.

doi:10.1200/jco.1998.16.3.937

Cited by 24 publications

(7 citation statements)

References 33 publications

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“…The incidence of oral and GI mucositis varied significantly among different treatment regimens and modalities (Table 4). 60–398 Most anthracycline‐based regimens were associated with rates of oral mucositis in the 1–10% range, except when regimens included 5‐FU. Included among these are the standard regimens for adjuvant therapy in patients with breast cancer (5‐FU, doxorubicin, and cyclophosphamide; doxorubicin and cyclophosphamide; or 5‐FU, epirubicin, and cyclophosphamide) as well as regimens for patients with non‐Hodgkin lymphomas, including cyclophosphamide, doxorubicin, vincristine, and prednisolone (CHOP).…”

Section: Epidemiology and Outcomesmentioning

confidence: 99%

Perspectives on cancer therapy-induced mucosal injury

Sonis

Elting

Keefe

et al. 2004

Cancer

1,246

478

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Section: Epidemiology and Outcomesmentioning

confidence: 99%

Perspectives on cancer therapy-induced mucosal injury

Sonis

Elting

Keefe

et al. 2004

Cancer

1,246

478

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“…In our group of patients transplanted from unrelated donors, conditioning with high‐dose l ‐PAM (210 mg/m 2 ), a dose commonly employed in the high‐dose therapy of many malignant diseases ( 1–7), and TBI appears to considerably increase the incidence of clinically severe acute GvHD, particularly involving the GI tract, when compared to patients treated with other preparative regimens. Furthermore, the risk of toxic death also appears to be higher among those conditioned with l ‐PAM and TBI.…”

Section: Discussionmentioning

confidence: 99%

“…When used in the high‐dose therapy of solid tumors with autologous stem cell rescue, l ‐PAM has been associated with mucositis (even severe), but relatively few toxic deaths and limited clinical GI toxicity in the form of diarrhea ( 4–6). When used as the sole high‐dose therapy with autolo‐gous stem cell rescue in the adult setting, severe mucositis was commonly encountered but without toxic deaths or significant clinical GI toxicity ( 7).…”

mentioning

confidence: 99%

Allograft with unrelated donor accentuates the gastrointestinal toxicity associated with high‐dose melphalan and total body irradiation preparative for bone marrow transplantation in children

Vettenranta

Hovi

Taskinen

et al. 2000

Pediatric Transplantation

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The use of high-dose melphalan (L-phenyalalanine mustard or L-PAM) has been shown to be associated with both hematological and non-hematological toxicity. It has been employed in the conditioning for allogeneic stem cell transplants from related donors but experience on its use in the unrelated setting has not been reported. As an attempt to elucidate the role of high-dose L-PAM (210 mg/m2) and total body irradiation (TBI) as a preparative regimen for allogeneic marrow transplantation from matched unrelated donors, they were employed in an institutional pilot series of seven pediatric patients. When compared with recipients of unrelated marrow grafts conditioned using other regimens, those treated with high-dose L-PAM experienced a markedly more severe acute graft-vs.-host disease (GvHD). The overall incidence of grade III-IV acute GvHD was higher (86% vs. 14%) among those treated with L-PAM. As judged by gastrointestinal (GI) symptoms, clinically significant (stages +2 to +4) gut GvHD was strikingly more prevalent among those treated with L-PAM (86% vs. 9%, p < 0.005). Toxic mortality prior to day + 100 was 29% in the L-PAM group and 9% in the non-L-PAM group of patients. With a mean follow-up of 21 months no increase in the incidence of chronic GvHD has been encountered among those conditioned with L-PAM. We conclude that the use of preparative L-PAM for allogeneic transplants from unrelated donors is associated with considerable procedure-related toxicity. We strongly suggest its use in this setting to be viewed with caution.

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“…Despite chemosensitivity, durable disease‐free survivals of 30% or less are achieved for metastatic or relapsed disease. These observations have seen the development of increasingly intensive protocols incorporating myeloablative regimens with stem cell support 8−18 . In each of these reports, single or tandem myeloablative autologous stem cell transplant (SCT) as consolidation following remission induction chemotherapy has not resulted in improvement in overall survival (OS).…”

Section: Details Of Therapy and Outcome Of Patients With Esmentioning

confidence: 99%

Staged autologous peripheral blood progenitor cell transplantation for Ewing sarcoma and rhabdomyosarcoma

Ritchie

Grigg

Roberts

et al. 2004

Internal Medicine Journal

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Ewing sarcoma (ES), predominantly affects children and young adults, is derived from primitive fetal cells, and characteristically displays rearrangement of chromosome 22. 1 Rhabdomyosarcoma is also a small round cell tumour of primitive mesenchymal cells, which can be difficult to distinguish from primitive ES and is often differentiated on the basis of cytogenetic abnormalities. 2 Combination chemotherapy protocols for ES and rhabdomyosarcoma utilising doxorubicin, vincristine, cyclophosphamide, ifosfamide, etoposide, or epirubicin result in overall response rates of 69% to 94% for ES 3-6 and 40% for adults with rhabdomyosarcoma. 7 Adverse prognostic features in both tumours include age of onset (adult/adolescent worse than paediatric) and distant (particularly bone marrow) metastases. 7,8 Despite chemosensitivity, durable disease-free survivals of 30% or less are achieved for metastatic or relapsed disease. These observations have seen the development of increasingly intensive protocols incorporating myeloablative regimens with stem cell support. [8][9][10][11][12][13][14][15][16][17][18] In each of these reports, single or tandem myeloablative autologous stem cell transplant (SCT) as consolidation following remission induction chemotherapy has not resulted in improvement in overall survival (OS). By combining initial remission induction with later SCT, the overall duration of therapy remains prolonged and the regimenrelated toxicity is increased, particularly secondary leukaemia with a cumulative risk of between 8% and 23%. 6,8,19 Multiple staged SCT in ES or rhabdomyosarcoma has not previously been reported in adult patients. Our unit has previously observed safety with high dose cyclophosphamide and epirubicin with stem cell rescue for the treatment of high-risk breast cancer. 20 This approach led us to offer staged SCT as first-line therapy in the case of ES, or as salvage therapy in the case of relapsed primitive rhabdomyosarcoma.We used multiple cycles of the most effective agents at maximally tolerated doses supported by peripheral blood progenitor cells (PBPC) in order to limit both the duration and toxicity of therapy and improve the outcome in this patient group. Tolerability, toxicity, event-free survival and OS were assessed in 10 consecutive patients undergoing staged autologous SCT for de novo ES ( n = 6) or refractory or relapsed rhabdomyosarcoma ( n = 4). Patients gave written consent to participate in the treatment protocol.ES patients received cyclophosphamide 2 g/m 2 i.v. followed by filgrastim 5 µ g/kg/day by s.c. injection for the purposes of stem cell mobilisation. PBPC were collected by apheresis with a target total of 8 × 10 6 CD34+ cells per kg. Each collection was aliquoted into four equal portions prior to cryopreservation. Where the number of CD34+ cells collected failed to reach the target, further collections were undertaken during the recovery phase of the first SCT. Patients then received two cycles of epirubicin 200 mg/m 2 i.v. over 12 h on day -3 and cyclophosphamide 4 g/m 2 i...

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Double-alkylator non-total-body irradiation regimen with autologous hematopoietic stem-cell transplantation in pediatric solid tumors.

Cited by 24 publications

References 33 publications

Perspectives on cancer therapy-induced mucosal injury

Perspectives on cancer therapy-induced mucosal injury

Allograft with unrelated donor accentuates the gastrointestinal toxicity associated with high‐dose melphalan and total body irradiation preparative for bone marrow transplantation in children

Staged autologous peripheral blood progenitor cell transplantation for Ewing sarcoma and rhabdomyosarcoma

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