autologous blood and marrow transplantation - Blog Science ...

Carella et al.
later, and the other patient died in CR of aspergillus at 4 months. Another patient
with progressive Hodgkin's disease is alive at 14 months and has chronic GVHD,
and the other died of progressive disease on day 65. The patient with low-grade
non-Hodgkin's lymphoma, who achieved PR after autografting, obtained a CR and
is disease-free 6 months after allografting. The other patient died of progressive
lymphoma 5 months after allografting. The patient with accelerated phase CML
obtained hematologic remission and is now in molecular remission 8 months later.
One patient with RAEB relapsed after achieving hematologic and cytogenetic
remission for 3 months. Severe acute GVHD (grade >II) was the single major
complication but caused no deaths. Mild acute GVHD was seen in another patient.
Only one patient experienced an absolute neutrophil count below 1X10 9
/L and in
no case did platelets decrease below 20X10 9
/L. No patients required sterile rooms
or any red cell or platelet transfusions. We conclude that immunosuppressive
therapy with the Flu-Cy protocol enabled the engraftment of HLA-matched sibling
donor stem cells without procedure-related deaths. Moreover, we have
demonstrated that this combined procedure can be pursued safely in a seriously ill
population, and some can achieve complete remission. This procedure is likely not
curative, but is a fascinating step along the path to curing these diseases.
INTRODUCTION
To circumvent the inherent problems of toxicity and treatment-related deaths
associated with allografting, it was recently shown that engraftment of donor
hematopoietic stem cells can be achieved after immunosuppressive therapy
combined with myelosuppressive but nonmyeloablative therapy. 12
The observations
that nonmyeloablative regimens based on fludarabine have resulted in engraftment of
allogeneic cells in patients with hematologic malignancies, raises the possibility that
such conditioning might be useful in achieving a graft-vs.-tumor effect. In this pilot
study, we treated nine patients with resistant malignancies who received high-dose
therapy and autologous stem cell transplantation as tumor debulky therapy followed
by immunosuppressive therapy and infusion of HLA-matched sibling donor stem
cells in an attempt to induce an immune-mediated antitumor effect.
PATIENTS AND METHODS
The patients were registered in the Hematology and ABMT Unit, Department
of Hematology, San Martino Hospital in Genoa. This pilot study was approved by
the Ethics Committee of San Martino Hospital, and informed consent was obtained
from patients and donors. Fourteen patients were treated, ages 22 to 57 years
(median age 40 years). Four had primarily refractory (n=2) or relapsed (n=2)
Hodgkin's disease and two had primarily refractory non-Hodgkin's lymphoma
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