VI Autologous Bone Marrow Transplantation.pdf - Blog Science ...

HIGH DOSE CHEMOTHERAPY AND AUTOLOGOUS BONE MARROW
RESCUE IN POOR RISK SARCOMA PATIENTS. REPORT OF PILOT
STUDY IN PEDIATRIC SARCOMAS.
By: J.M. Wiley, L.C. Strauss, A. Fresia A.M. Yeager, CI. Civin
and B.G. Leventhal.
The Johns Hopkins Oncology Center, Baltimore, Maryland. U.S.A.
Primary solid tumors account for approximately 30% of all childhood malignancies.
Sarcomas comprise approximately 1 /4 to 1 /3 of pediatric solid tumors
and 1% of adult malignancies. Despite many advances in the understanding
of the molecular biology and tumor cellular genetics, therapeutic options for
these tumors remain limited. Treatment of localized disease utilizing the combined
modalities of surgery, chemotherapy and radiotherapy results in excellent
long term disease free survival in selected tumors. This is especially true for
childhood rhabdomyosarcoma, osteogenic sarcoma and soft tissue sarcomas 1.
However, results for treatment of advanced or relapsed sarcomas remain poor
and new therapeutic modalities must be pursued.
The use of more intensive chemotherapy regimens with or without cytokine
support have been demonstrated to improve prognosis in poor risk patients.
The use of ifosfamide has improved response in combination therapies for patients
with Ewing's sarcoma, rhabdomyosarcoma and soft tissue sarcoma 2. Additionally,
intensification of regimens utilizing cyclophosphamide, cisplatin and
adriamycin have resulted in improved response rates in poor risk patients 3,4.
These data are strongly suggestive of a dose response effect for certain chemotherapeutic
agents in sarcomas.
The use of high dose chemotherapy with autologous bone marrow rescue
(ABMR) has been well studied in the lymphohematopoietic malignancies. However,
fewer studies have been done in solid tumors for a variety of reasons including
poor response rates with leukemia transplant regimens, development of
multidrug resistance in the solid tumor and a less committed approach to transplant
for these malignancies. More recently, studies using high dose chemotherapy
and ABMR in Ewing's sarcoma, rhabdomyosarcoma, testicular carcinoma
and a variety of other tumor types have demonstrated promise for this
approach 5-7. A number of phase I-II trials in adult solid tumors have demonstrated
the effectiveness of high dose combination treatments utilizing cyclophosphamide
(CY) or ifosfamide (IFOS), etoposide (VP-16), thiotepa, melphalan
(L-PAM), or carboplatin (CBDCA) 8-10. In many of these regimens dose intensity
of 5-10 fold for the combinations has been achieved.
The prognosis for refractory or metastatic pediatric solid tumors is very
poor with truly resistant patients having