CHEMOTHERAPY PROGRAMS TO GENERATE DIPLOID CELLS FOR AUTOLOGOUS BMT

  • Claxton, David (PI)
  • DEISSEROTH, ALBERT (PI)
  • CHAMPLIN, RICHARD (PI)
  • CHAMPLIN, RICHARD (PI)
  • DEISSEROTH, ALBERT (PI)
  • Kantarjian, Hagop (PI)
  • LEE, MING-SHENG (PI)
  • Talpaz, Moshe (PI)
  • EMERSON, STEPHEN (PI)
  • CHAMPLIN, RICHARD (PI)
  • DEISSEROTH, ALBERT (PI)
  • READING, CHRISTOPHER (PI)
  • KURZROCK, RAZELLE (PI)
  • Andreeff, Michael (PI)
  • Feinberg, Andrew (PI)
  • SICILIANO, MICHAEL (PI)
  • LIANG, JAN (PI)
  • Kantarjian, Hagop (PI)
  • Feinberg, Andrew (PI)
  • KORNBLAU, STEVEN (PI)
  • AUSTIN, DAVID (PI)
  • REISNER, YAIR (PI)
  • ARLINGHAUS, RALPH BERNARD (PI)
  • Talpaz, Moshe (PI)
  • SICILIANO, MICHAEL (PI)
  • THALL, PETER (PI)
  • Belmont, John (PI)
  • Estrov, Zeev (PI)
  • Andreeff, Michael (PI)
  • Kantarjian, Hagop (PI)
  • LEE, MING-SHENG (PI)
  • EMERSON, STEPHEN (PI)
  • READING, CHRISTOPHER (PI)
  • KURZROCK, RAZELLE (PI)
  • LIANG, JAN (PI)
  • CHAMPLIN, RICHARD (PI)
  • Cortés, Jorge (PI)
  • Andreeff, Michael (PI)
  • DEININGER, MICHAEL (PI)
  • ARLINGHAUS, RALPH BERNARD (PI)
  • ISSA, KEAN-PIERRE (PI)
  • THALL, PETER (PI)
  • Estrov, Zeev (PI)
  • KORNBLAU, STEVEN (PI)
  • SHPALL, ELIZABETH (PI)
  • ISSA, JEAN-PIERRE (PI)
  • Andreeff, Michael (PI)
  • Andreeff, Michael (PI)
  • Andreeff, Michael (PI)
  • CHAMPLIN, RICHARD (PI)
  • Andreeff, Michael (PI)

Project: Research project

Project Details

Description

Interferon therapy can induce cytogenetic remissions which last for years
in 26% of early chronic phase CML patients, but the remissions are
produced only after long periods of daily therapy, often requiring months
to years to achieve major or complete cytogenetic remission. In contrast,
intensive but not ablative does of combination chemotherapy (such as
Daunomycin Ara-C) rapidly produce major cytogenetic remissions in 30% of
patients, but these remissions do not last for more than a few months. We
have embarked upon a program to develop chemotherapy based alternatives
for the therapy of CML patients who are interferon-resistant and do not
have allograft donors. The goal of this program is to use chemotherapy to
generate diploid (normal) cells for use in autologous bone marrow
transplantation. To accomplish this, we have searched for forms of
chemotherapy which are associated with more durable periods of
myelosuppression than is the case with conventional dose chemotherapy, but
are less toxic than standard chemotherapy. We also are collecting
peripheral blood cells in the early stages of hematopoietic recovery at a
time when diploid cells dominate the progenitor population. In addition,
we use ex vivo fractionation of early hematopoietic progenitor cells to
obtain populations of autologous marrow and peripheral blood which are
enriched in diploid cells. We infuse these fractionated autologous cells,
which are enriched in diploid cells, following systemic intensive
therapeutic regimens which are ablative. We have developed very promising
early clinical results with the chemotherapeutic agent, homoharringtonine
(HHT), which are using in untreated patients. The myelosuppressive effect
of HHT is more durable than that seen with conventional forms of
chemotherapy. HHT produces major cytogenetic remissions in 33% of the
early chronic phase patients treated. In addition, the clinical
experience so far accumulated with the autologous transplant program
suggests that chemotherapy with the combinations of fludarabine, Ara-C and
mitoxantrone (FAM) or Daunomycin high dose Ara-C (DARAC) followed by CD34
selection, and autologous bone marrow transplant with the autologous cells
selected ex vivo can produce major or complete cytogenetic remissions in
interferon-resistant late chronic phase patients so treated, and that
minor cytogenetic remissions with this program can be achieved even with
accelerated phase or blast crisis patients. The PCR assay, the rare
immunophenotype assay, and the metaphase FISH assay are used to measure
response, and to optimize the formulation of this therapy so as to promote
the collection of autologous diploid cells on the maximum number of
diploid cells. We also hope to attempt to identify surrogate molecular
endpoints for prolonged remission duration or survival. The work proposed
in this project is designed to increase the number of patients who are
eligible for autologous marrow transplants. Dr. Gehan and Terry Smith
will work with us on this program and all clinical and laboratory programs
to evaluate the correlations between laboratory data and clinical outcome
in the therapeutic programs.
StatusFinished
Effective start/end date1/1/016/30/16

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