Ablative Therapy Supported by Autologous Bone Marrow Transplantation with In Vitro Treatment of Marrow in Patients with B-Cell Malignancy

1987 ◽  
pp. 59-61
Author(s):  
A. Z. S. Rohatiner ◽  
M. J. Barnett ◽  
S. Arnott ◽  
N. Plowman ◽  
F. Cotter ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Bone Marrow Transplantation ◽  
B Cell ◽  
Marrow Transplantation ◽  
Autologous Bone Marrow Transplantation ◽  
Autologous Bone Marrow ◽  
B Cell Malignancy ◽  
Autologous Bone ◽  
In Vitro Treatment

scholarly journals Autologous bone marrow transplantation for patients with acute lymphoblastic leukemia in second or subsequent remission: results of bone marrow treated with monoclonal antibodies BA-1, BA-2, and BA-3 plus complement

Blood ◽  
1985 ◽  
Vol 66 (3) ◽  
pp. 508-513 ◽  
Author(s):  
N Ramsay ◽  
T LeBien ◽  
M Nesbit ◽  
P McGlave ◽  
D Weisdorf ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Monoclonal Antibodies ◽  
Acute Lymphoblastic Leukemia ◽  
Bone Marrow Transplantation ◽  
Marrow Transplantation ◽  
Lymphoblastic Leukemia ◽  
Autologous Bone Marrow Transplantation ◽  
Autologous Bone Marrow ◽  
Autologous Bone

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.

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 ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Bone Marrow Transplantation ◽  
Marrow Transplantation ◽  
Blast Crisis ◽  
Autologous Bone Marrow Transplantation ◽  
Chronic Phase ◽  
Autologous Bone Marrow ◽  
Myelogenous Leukemia ◽  
Autologous Bone

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.

scholarly journals Autologous bone marrow transplantation in acute leukemia: a phase I study of in vitro treatment of marrow with 4- hydroperoxycyclophosphamide to purge tumor cells

Blood ◽  
1985 ◽  
Vol 65 (6) ◽  
pp. 1504-1510 ◽  
Author(s):  
H Kaizer ◽  
RK Stuart ◽  
R Brookmeyer ◽  
WE Beschorner ◽  
HG Braine ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Bone Marrow Transplantation ◽  
Acute Leukemia ◽  
Phase I Study ◽  
Autologous Bone Marrow Transplantation ◽  
Autologous Bone Marrow ◽  
Autologous Bone ◽  
In Vitro Treatment ◽  
Safe Concentration

Abstract This phase I study was conducted to determine the maximal safe concentration of 4-hydroperoxycyclophosphamide (4HC) that could be used for in vitro treatment of bone marrow from patients with acute leukemia undergoing autologous bone marrow transplantation. Concentrations of 40 to 120 micrograms/mL of 4HC were used in 30 patients with relapsed or high-risk acute leukemia and in six patients with nonleukemic malignancies. All patients received marrow-lethal cytoreductive therapy followed by infusion of the 4HC-treated marrow. Complete inhibition of granulocyte and macrophage colony-forming cells was obtained at 80 micrograms/mL. Nevertheless, only one transplant-related death and otherwise full hematologic recovery was observed at concentrations of 4HC up to 100 micrograms/mL. At 120 micrograms/mL, there were three transplant-related deaths, including two of the three patients who required the infusion of reserve marrow. Among the acute leukemia patients, three remain in complete remission at 1,337, 1,017, and 967 days after transplant. Among the nonleukemic patients, two remain in complete remission at 1,081 and 1,017 days after transplant. At the maximum safe concentration of 4HC (100 micrograms/mL), satisfactory hematologic recovery can be obtained, despite elimination of detectable hematopoietic progenitors.

Detection of cells bearing the t(14;18) translocation following myeloablative treatment and autologous bone marrow transplantation for follicular lymphoma.

1994 ◽  
Vol 12 (4) ◽  
pp. 798-805 ◽  
Author(s):  
P W Johnson ◽  
C G Price ◽  
T Smith ◽  
F E Cotter ◽  
J Meerabux ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Bone Marrow Transplantation ◽  
Follicular Lymphoma ◽  
Mononuclear Cell ◽  
Marrow Transplantation ◽  
Autologous Bone Marrow Transplantation ◽  
Autologous Bone Marrow ◽  
Autologous Bone

PURPOSE To use the polymerase chain reaction (PCR) technique for molecular assessment of the results of myeloablative treatment of follicular lymphoma with autologous bone marrow transplantation. PATIENTS AND METHODS Seventy-six patients with follicular or transformed follicular lymphoma were treated with cyclophosphamide 60 mg/kg x 2 and total-body irradiation 12 Gy, supported by autologous bone marrow transplantation. The bone marrow mononuclear cell fraction was treated in vitro with CD20 monoclonal antibody and baby rabbit complement. The PCR technique was used to identify 50 patients with amplifiable t(14; 18) translocations in biopsy material from lymph nodes or bone marrow infiltrated by lymphoma. RESULTS Following treatment of the harvested bone marrow in vitro, 29 samples were tested by PCR to assess the efficacy of purging. In 25 cases, the same t(14; 18) sequences were amplified as from the patients' original biopsies, while in four cases, the marrow became PCR-negative. Three of the four patients treated with PCR-negative marrow subsequently developed recurrent lymphoma, compared with 11 of 25 in the PCR-positive group. Bone marrow and peripheral-blood mononuclear cell samples from 27 patients were studied during the follow-up period. All but one had the presence of the lymphoma-related t(14; 18) clone detectable by PCR and confirmed by direct sequencing from at least one sample between 3 months and 7 years after reinfusion of the bone marrow. With a median follow-up duration of 3 years, 13 patients developed recurrent disease, 13 remained in remission with the t(14; 18) still detectable, and one died of acute myeloid leukemia. CONCLUSION This form of therapy does not eliminate the lymphoma-related t(14; 18)-bearing clone of cells, although the significance of its continued presence is uncertain. Improved methods for both treatment of the bone marrow in vitro and treatment of the lymphoma in vivo are required.

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