scholarly journals BCR-ABL Antisense Oligodeoxynucleotide In Vitro Purging and Autologous Bone Marrow Transplantation for Patients With Chronic Myelogenous Leukemia in Advanced Phase

Blood ◽  
1998 ◽  
Vol 91 (9) ◽  
pp. 3156-3162 ◽  
Author(s):  
Paolo de Fabritiis ◽  
Maria Concetta Petti ◽  
Enrico Montefusco ◽  
Maria Stefania De Propris ◽  
Roberta Sala ◽  
...  

BCR-ABL antisense oligodeoxynucleotides (ODN) have provided evidence of antileukemia effect when tested in vitro against Philadelphia-positive (Ph-pos) cells and in vivo when injected into leukemic mice. On the basis of the results obtained in vitro at diagnosis, eight patients with chronic myelogenous leukemia (CML) were selected and submitted to autologous bone marrow transplantation (ABMT) with bone marrow (BM) cells purged in vitro with junction-specific (J-sp) BCR-ABL antisense ODN at the time of transformation in accelerated phase or during second chronic phase. Mononuclear BM cells were treated in vitro for 24 or 72 hours with 150 μg/mL of antisense ODN yielding a median recovery of 47.6% mononuclear cells, 48.8% CD34+ cells, and 20.3% clonogenic cells. After a conditioning regimen including busulphan and etoposide, the reinfused treated cells allowed engraftment and hematologic reconstitution in all patients. Evaluation of the antileukemic effect by standard cytogenetic analysis and fluorescence in situ hybridization showed a complete karyotypic response in two cases and a minimal or no response in the other six. The patient autografted in second chronic phase died in blast crisis 7 months after ABMT; of the seven patients autografted in transformation, three developed blast crisis 21 to 39 months after reinfusion, one died from unrelated BMT complications 30 months after ABMT, and three are in persistent second chronic phase 14 to 26 months after autograft. The low toxicity of the protocol and the hemopoietic reconstitution observed in all patients make this approach feasible; the marked karyotypic response observed in some patients and the duration of the second chronic phase show that ODN-mediated BM purging and autograft is a promising treatment for this high-risk group of CML.

Blood ◽  
1998 ◽  
Vol 91 (9) ◽  
pp. 3156-3162 ◽  
Author(s):  
Paolo de Fabritiis ◽  
Maria Concetta Petti ◽  
Enrico Montefusco ◽  
Maria Stefania De Propris ◽  
Roberta Sala ◽  
...  

Abstract BCR-ABL antisense oligodeoxynucleotides (ODN) have provided evidence of antileukemia effect when tested in vitro against Philadelphia-positive (Ph-pos) cells and in vivo when injected into leukemic mice. On the basis of the results obtained in vitro at diagnosis, eight patients with chronic myelogenous leukemia (CML) were selected and submitted to autologous bone marrow transplantation (ABMT) with bone marrow (BM) cells purged in vitro with junction-specific (J-sp) BCR-ABL antisense ODN at the time of transformation in accelerated phase or during second chronic phase. Mononuclear BM cells were treated in vitro for 24 or 72 hours with 150 μg/mL of antisense ODN yielding a median recovery of 47.6% mononuclear cells, 48.8% CD34+ cells, and 20.3% clonogenic cells. After a conditioning regimen including busulphan and etoposide, the reinfused treated cells allowed engraftment and hematologic reconstitution in all patients. Evaluation of the antileukemic effect by standard cytogenetic analysis and fluorescence in situ hybridization showed a complete karyotypic response in two cases and a minimal or no response in the other six. The patient autografted in second chronic phase died in blast crisis 7 months after ABMT; of the seven patients autografted in transformation, three developed blast crisis 21 to 39 months after reinfusion, one died from unrelated BMT complications 30 months after ABMT, and three are in persistent second chronic phase 14 to 26 months after autograft. The low toxicity of the protocol and the hemopoietic reconstitution observed in all patients make this approach feasible; the marked karyotypic response observed in some patients and the duration of the second chronic phase show that ODN-mediated BM purging and autograft is a promising treatment for this high-risk group of CML.


1986 ◽  
Vol 4 (6) ◽  
pp. 906-911 ◽  
Author(s):  
L Vellekoop ◽  
A R Zander ◽  
H M Kantarjian ◽  
S Jagannath ◽  
J P Hester ◽  
...  

Eleven patients with Philadelphia chromosome (Ph1)-positive chronic myelogenous leukemia (CML) in blast crisis (ten patients) or accelerated disease (one patient) were treated with piperazinedione (PIP) and fractionated total body irradiation (TBI) followed by autologous bone marrow transplantation (ABMT). Three patients were transplanted with marrow from which the Ph1 clone had been eradicated by prior intensive chemotherapy. All patients responded with disappearance of blasts in bone marrow and peripheral blood. Six patients achieved a second chronic phase lasting 3 to 14 months (median, 6 months). Two patients had incomplete recovery, and three patients failed to engraft and died from infection. Transplantation with Ph1-negative bone marrow did not improve response duration or survival. Recurrence of blast crisis and incomplete engraftment continue to be the two major problems in this patient group, and more active regimens need to be investigated.


1983 ◽  
Vol 69 (3) ◽  
pp. 239-248
Author(s):  
Pietro Muretto ◽  
Teodosio Izzi ◽  
Cesare Grianti ◽  
Luciano Moretti

Twenty-six patients with acute myeloid leukemia, acute lymphoid leukemia and chronic granulocytic leukemia in blast crisis were studied by means of multiple biopsies during a polychemotherapeutic or autologous bone marrow transplant protocol. Following chemotherapy, 3 main phases were observed: leukemic cellular depletion, stromal bone marrow reconstruction, and bone marrow hemopoietic restoration. Following intensive chemotherapy (in 2 patients after cyclophosphamide and total body irradiation) and autologous bone marrow transplantation, the 3 phases appeared to be shorter. A focal or diffuse increase in marrow fibrosis was a common finding in leukemia. An effective antileukemic therapy resulted in a decrease in fibrosis, whereas in some cases a further increase was a precocious sign of leukemia relapse.


Blood ◽  
1985 ◽  
Vol 66 (3) ◽  
pp. 508-513 ◽  
Author(s):  
N Ramsay ◽  
T LeBien ◽  
M Nesbit ◽  
P McGlave ◽  
D Weisdorf ◽  
...  

Abstract Autologous bone marrow transplantation (BMT) was utilized as therapy for 23 patients with acute lymphoblastic leukemia (ALL) in second or greater remission. Bone marrow was treated in vitro with a combination of monoclonal antibodies, consisting of BA-1, BA-2, BA-3, and baby rabbit complement (BRC'). All patients were prepared for transplantation with cyclophosphamide and fractionated total body irradiation. Engraftment occurred in all 23 patients. Seven of 23 patients remain relapse-free from six to 32 months (median, 21.4 months) posttransplant. Failures were due to relapse with the exception of one patient who died of infection. This study demonstrates that autologous BMT using in vitro marrow treatment with BA-1, BA-2, BA-3, and BRC' is safe, allows engraftment, and results in prolonged survival for some patients with ALL in second or greater remission.


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