Therapy of acute phase chronic myelogenous leukemia with intensive chemotherapy, blood cell autotransplant and cyclosporine A

A. M. Carella, E. Gaozza, M. R. Raffo, P. Carlier, F. Frassoni, M. Valbonesi, G. Lercari, M. Sessarego, R. Defferrari, A. Guerrasio, G. Saglio, L. Canepa, G. F. Gaetani, D. Occhini

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Abstract

The expansion of the Philadelphia (Ph) chromosome positive clone in chronic myeloid leukemia (CML) may depend on its capacity to suppress the proliferation of Ph-negative stem cells, but this proliferative advantage might, in certain circumstances, be reversible. Various lines of evidence suggest that Ph-negative cells, albeit in a suppressed state, must still be present. As recently suggested, the expansion of 'putative' normal Ph-negative hemopoietic stem cells might have, in certain circumstances, a proliferative advantage over the Ph clone in CML. This suggests that the treatment of CML with intensive chemotherapy might allow the collection of Ph-negative hemopoietic cells in the early phase of recovery. Eight patients with acute phase chronic myelogenous leukemia (AP-CML) were treated with idarubicin, intermediate dose cytarabine and etoposide. During recovery from bone marrow aplasia, when the white blood cell count reached 0.3-1×10-9, blood cells were collected with 2-5 (median 3) consecutive leukapheresis. In 5/8 patients, these peripheral cells were Ph-negative at the cytogenetic analysis. Moreover, in one case the polymerase chain reaction analysis performed to detect the presence of minimal residual disease in the cells collected by leukapheresis was negative, further confirming that this approach may induce a very high degree of suppression of the Ph-positive clones. After complete recovery, these five patients were subsequently treated with high-dose etoposide, cyclophosphamide and total body radiation (10Gy, single dose) followed by reinfusion of Ph-negative peripheral blood stem cells. All these patients received cyclosporine A post-autotransplant in an attempt to induce acute graft-versus-hostdisease. Three of 5 patients remain in clinical and cytogenetic remission 5-15 months post-transplant. It is concluded that Ph-negative peripheral blood stem cells can be recovered from patients with AP-CML and used successfully to restore Ph-negative hemopoiesis after high dose therapy.

Original languageEnglish
Pages (from-to)517-521
Number of pages5
JournalLeukemia
Volume5
Issue number6
Publication statusPublished - Jun 1991

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Leukemia, Myeloid, Chronic Phase
Autografts
Cyclosporine
Blood Cells
Drug Therapy
Leukemia, Myelogenous, Chronic, BCR-ABL Positive
Leukapheresis
Therapeutics
Clone Cells
Etoposide
Stem Cells
Idarubicin
Transplants
Philadelphia Chromosome
Cytogenetic Analysis
Cytarabine
Residual Neoplasm
Leukocyte Count
Cytogenetics
Cyclophosphamide

ASJC Scopus subject areas

  • Cancer Research
  • Hematology

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Therapy of acute phase chronic myelogenous leukemia with intensive chemotherapy, blood cell autotransplant and cyclosporine A. / Carella, A. M.; Gaozza, E.; Raffo, M. R.; Carlier, P.; Frassoni, F.; Valbonesi, M.; Lercari, G.; Sessarego, M.; Defferrari, R.; Guerrasio, A.; Saglio, G.; Canepa, L.; Gaetani, G. F.; Occhini, D.

In: Leukemia, Vol. 5, No. 6, 06.1991, p. 517-521.

Research output: Contribution to journalArticle

Carella, AM, Gaozza, E, Raffo, MR, Carlier, P, Frassoni, F, Valbonesi, M, Lercari, G, Sessarego, M, Defferrari, R, Guerrasio, A, Saglio, G, Canepa, L, Gaetani, GF & Occhini, D 1991, 'Therapy of acute phase chronic myelogenous leukemia with intensive chemotherapy, blood cell autotransplant and cyclosporine A', Leukemia, vol. 5, no. 6, pp. 517-521.
Carella, A. M. ; Gaozza, E. ; Raffo, M. R. ; Carlier, P. ; Frassoni, F. ; Valbonesi, M. ; Lercari, G. ; Sessarego, M. ; Defferrari, R. ; Guerrasio, A. ; Saglio, G. ; Canepa, L. ; Gaetani, G. F. ; Occhini, D. / Therapy of acute phase chronic myelogenous leukemia with intensive chemotherapy, blood cell autotransplant and cyclosporine A. In: Leukemia. 1991 ; Vol. 5, No. 6. pp. 517-521.
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abstract = "The expansion of the Philadelphia (Ph) chromosome positive clone in chronic myeloid leukemia (CML) may depend on its capacity to suppress the proliferation of Ph-negative stem cells, but this proliferative advantage might, in certain circumstances, be reversible. Various lines of evidence suggest that Ph-negative cells, albeit in a suppressed state, must still be present. As recently suggested, the expansion of 'putative' normal Ph-negative hemopoietic stem cells might have, in certain circumstances, a proliferative advantage over the Ph clone in CML. This suggests that the treatment of CML with intensive chemotherapy might allow the collection of Ph-negative hemopoietic cells in the early phase of recovery. Eight patients with acute phase chronic myelogenous leukemia (AP-CML) were treated with idarubicin, intermediate dose cytarabine and etoposide. During recovery from bone marrow aplasia, when the white blood cell count reached 0.3-1×10-9, blood cells were collected with 2-5 (median 3) consecutive leukapheresis. In 5/8 patients, these peripheral cells were Ph-negative at the cytogenetic analysis. Moreover, in one case the polymerase chain reaction analysis performed to detect the presence of minimal residual disease in the cells collected by leukapheresis was negative, further confirming that this approach may induce a very high degree of suppression of the Ph-positive clones. After complete recovery, these five patients were subsequently treated with high-dose etoposide, cyclophosphamide and total body radiation (10Gy, single dose) followed by reinfusion of Ph-negative peripheral blood stem cells. All these patients received cyclosporine A post-autotransplant in an attempt to induce acute graft-versus-hostdisease. Three of 5 patients remain in clinical and cytogenetic remission 5-15 months post-transplant. It is concluded that Ph-negative peripheral blood stem cells can be recovered from patients with AP-CML and used successfully to restore Ph-negative hemopoiesis after high dose therapy.",
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AU - Lercari, G.

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