Autologous Bone Marrow Transplantation - Blog Science Connections

408 ABMTin 65 Patients With Neuroblastoma
preliminary results from using intensive therapy and ABMT as early consolidation
for stage IV neuroblastoma in children over 1 year of age who are either
in partial remission (PR) or complete remission (CR) (6-9). A randomized
study of the use of high-dose melphalan alone with unpurged marrow as
consolidation of first CR is now in progress under the responsibility of the
European Neuroblastoma Study Group (ENSG) (11,12, and T. Philip et al. "A
Single Institution's Experience of Autologous Bone Marrow Transplantation
for Neuroblastoma," this volume).
Extensive bone marrow staging procedures have shown clearly that at
least 25% of patients in so-called CR still have some malignant cells in their
bone marrow (9,13). These clinical observations, linked with those of the
various animal models in leukemia, which showed that no more than one or
two reinjected cells might explain failure after ABMT (14,15), were the
background for setting up ex vivo procedures to try to purge the remaining
malignant cells prior to ABMT in neuroblastoma. An in vitro purging
procedure with Asta Z, the stable active metabolite of cyclophosphamide
(4-OH-cyclophosphamide or mafosfamide) is widely used despite little clear
evidence of its efficacy in vitro (6). The 6-OH-dopamine purging procedure
has been shown to be clinically feasible (9,16), but in vitro data have shown
that this technique alone will not produce more than a 1 -log reduction of
tumor cell load (16). For immunological purging procedures, complement
lysis techniques were unsuitable because of the absence of cytotoxicity with
use of the majority of the currently available monoclonal antibodies (2). The
development of an immunomagnetic technique suitable for ex vivo treatment
provided an alternative method of utilizing monoclonal antibodies (17-21;
see also Combaret er al. "Eliminating Burkitt's Cells From Excess Bone
Marrow With an Immunomagnetic Purging Procedure" and Favrot et al.
"Comparative Efficiency of an Immunomagnetic Purging Procedure and a
Rabbit Complement Lysis for Eliminating Burkitt's Cells From Bone Marrow,"
both in this volume).
In this report we analyze our experience since 1983 of the use of intensive
therapy as consolidation for an unselected group of patients older than 1 year
who have stage IV neuroblastoma.
PATIENTS AND METHODS
Patients
All patients with stage IV neuroblastoma according to Evans et al. (22)
and more than 1 year of age entered the pilot protocol. The first 37 patients
received induction regimens including cisplatin, epidophyllotoxin, VM-26
(teniposide) alternating with cyclophosphamide, Adriamycin (doxorubicin),
and vincristine (PE/CADO). Surgerywas performed after a maximum tumor
regression (i.e., four courses of chemotherapy in most cases). After surgery
four additional courses of conventional therapy were given, except for four