Intensive Treatment in order to Minimize the Ph-Positive Clone in Chronic Myelogenic Leukemia

Abstract

Philadelphia-chromosome metaphases in 57% of the patients (7% became Phnegative). The corresponding ngureS after two intensive cytotherapies were 70% (40% Ph-negative). Eighteen patients were autotrausplanted. Seven have relapsed with Ph-positivity 3-22 months after ABMT, while nine are Ph-negative at 1-32+ months after ABMT (two not yet analyzed). Seventeen patients are alive and well, while one died one month rreatmen~ Ph-analysis was performed. Patients with Press 1066-5099/93/$5.00/0 after ABMT due to interstitial pneumonia. Of the remaining 79 patients, 32 are in continuous chronic phase, 34 were allotramplanted and 13 have died (three during Daunorubicin Ara-C [DA]) treatment, one refusing transfusions, nine in blastic transformation). We conclude that intensive treatment effectively reduces the Ph-positive clone in CML. Bone marrow can remain Ph-negative for 32+ months after ABMT. A long follow-up is needed to see whether this treatment prolongs time to metamorphosis.

Mobilisation of haemopoietic progenitors in CML: a second course of intensive chemotherapy does not improve Ph-negativity in stem cell harvests

“…If Ph-negativity occurred after one to three cycles, bone marrow was harvested and patients were autotransplanted, yielding posttransplant cytogenetic remissions of various duration and an overall survival that seemed to be better than that of a group of age-matched historical controls. 36 These favourable results may suggest that intensive chemotherapy also effectively reduces the leukemic burden in the patient, apart from a graft-purging effect. Thus, according to the data listed in Table 4, at least 50% major cytogenetic responses may be achieved with current mobilisation regimens, primarily depending on disease stage.…”

“…35 A positive effect on the elimination of malignant progenitors was suggested. Ph-negativity increased after consecutive cycles of intensive chemotherapy.…”

Collection of Philadelphia-negative peripheral blood progenitor cells in unselected patients with chronic granulocytic leukaemia

“…Total registration of all new cases of CGL has been in place since January 1988. A median of 25 new cases present per annum (range [16][17][18][19][20][21][22][23][24][25][26][27][28][29]. 4 From January 1994 a programme of early intervention for patients under 60 years of age was begun with the cooperation of all 25 regional haematologists.…”

“…12 Recently some centres have reported attempts to improve the quality of autologous material available for transplant by eliminating or reducing the size of the Ph-positive clone. 9,[13][14][15][16][17] In some patients it is possible to collect autologous haemopoietic peripheral blood progenitor cells (PBPC) of which only a minority may be Ph positive. A number of transplants have now been performed using these cells with encouraging results.…”

Negative selection and protection of normal progenitor cells for autografting

“…There is clear evidence of the clinical benefits of high-dose therapy with ABMT for the treatment of acute leukemias, [3][4][5][6][7] non-Hodgkin's lymphoma, [8][9][10][11] Hodgkin's disease, 10 multiple myeloma, 12 breast cancer, [13][14][15] and germ cell carcinoma of the testes. 16 Studies examining ABMT or PBSC reinfusion are also underway for patients with chronic myelogenous leukemia [17][18][19] and neuroblastoma. 20 Although treatment-related complications are less likely to arise with ABMT than with alloBMT, ABMT suffers from two drawbacks that may be responsible for the higher relapse rate seen with this procedure.…”