scholarly journals Purging murine leukemic marrow with alkyl-lysophospholipids

Blood ◽  
1984 ◽  
Vol 64 (6) ◽  
pp. 1288-1291 ◽  
Author(s):  
L Glasser ◽  
LB Somberg ◽  
WR Vogler
Keyword(s):  
Stem Cells ◽  
Bone Marrow ◽  
Cytotoxic Effect ◽  
Autologous Bone Marrow Transplantation ◽  
Autologous Bone Marrow ◽  
Leukemic Cells ◽  
Hematopoietic Stem ◽  
Myelomonocytic Leukemia ◽  
In Vitro Treatment

Abstract Autologous bone marrow transplantation is potentially curative in the treatment of acute leukemia if residual leukemic cells in the marrow can be eliminated prior to transplantation. We studied the purging effects of a synthetic alkyl-lysophospholipid (ALP) on marrow containing leukemic cells from a transplantable myelomonocytic leukemia (WEHI-3B) in BALB/c mice. Simulated remission bone marrow containing 2% leukemic cells treated in vitro with 20 and 100 micrograms/mL of ET-18- OCH3 (1-octadecyl-2-methyl-sn-glycerol-3-phosphocholine) significantly prolonged survival of lethally irradiated transplanted recipients. At a dose of 100 micrograms/mL, 88% of the mice survived for the duration of the experiment (approximately five months). Autopsies showed that 25% of these survivors had microscopic evidence of leukemia. Thus, in vitro treatment of marrow eliminated leukemic blasts and spared sufficient normal stem cells to allow hematologic reconstitution. The effect of ET- 18-OCH3 is not entirely selective for leukemic cells. A spleen colony assay showed that ALP has some cytotoxic effect on normal hematopoietic stem cells.

scholarly journals Purging murine leukemic marrow with alkyl-lysophospholipids

Blood ◽  
1984 ◽  
Vol 64 (6) ◽  
pp. 1288-1291
Author(s):  
L Glasser ◽  
LB Somberg ◽  
WR Vogler
Keyword(s):  
Stem Cells ◽  
Bone Marrow ◽  
Cytotoxic Effect ◽  
Autologous Bone Marrow Transplantation ◽  
Autologous Bone Marrow ◽  
Leukemic Cells ◽  
Hematopoietic Stem ◽  
Myelomonocytic Leukemia ◽  
In Vitro Treatment

Autologous bone marrow transplantation is potentially curative in the treatment of acute leukemia if residual leukemic cells in the marrow can be eliminated prior to transplantation. We studied the purging effects of a synthetic alkyl-lysophospholipid (ALP) on marrow containing leukemic cells from a transplantable myelomonocytic leukemia (WEHI-3B) in BALB/c mice. Simulated remission bone marrow containing 2% leukemic cells treated in vitro with 20 and 100 micrograms/mL of ET-18- OCH3 (1-octadecyl-2-methyl-sn-glycerol-3-phosphocholine) significantly prolonged survival of lethally irradiated transplanted recipients. At a dose of 100 micrograms/mL, 88% of the mice survived for the duration of the experiment (approximately five months). Autopsies showed that 25% of these survivors had microscopic evidence of leukemia. Thus, in vitro treatment of marrow eliminated leukemic blasts and spared sufficient normal stem cells to allow hematologic reconstitution. The effect of ET- 18-OCH3 is not entirely selective for leukemic cells. A spleen colony assay showed that ALP has some cytotoxic effect on normal hematopoietic stem cells.

scholarly journals Autologous peripheral hematopoietic stem cell transplantation restores hematopoietic function following marrow ablative therapy

Blood ◽  
1988 ◽  
Vol 71 (3) ◽  
pp. 723-727 ◽  
Author(s):  
A Kessinger ◽  
JO Armitage ◽  
JD Landmark ◽  
DM Smith ◽  
DD Weisenburger
Keyword(s):  
Stem Cells ◽  
Bone Marrow ◽  
Stem Cell ◽  
Autologous Bone Marrow Transplantation ◽  
Hemoglobin Concentration ◽  
Autologous Bone Marrow ◽  
Normal Numbers ◽  
Hematopoietic Stem ◽  
Ablative Therapy ◽  
To Receive

Abstract From ten patients with advanced malignant disease involving the bone marrow, autologous hematopoietic stem cells were collected from the peripheral blood during eight four-hour pheresis procedures and cryopreserved. No manipulations to increase the number of stem cells circulating in the blood were used during the collections. Following marrow ablative chemotherapy or chemoradiotherapy, the autologous cells were thawed and infused intravenously (IV). WBCs reappeared in the circulation at a median of eight days (range seven to 11 days) after stem cell infusion. Two patients died early, whereas the other eight reached normal numbers of circulating granulocytes that have persisted for up to greater than 20 months. These eight patients became independent of RBC transfusions (hemoglobin concentration greater than 10 g/dL) at a median of 27 days (range 11 to 58 days) after transplantation. One patient received platelet transfusions for counts less than 50 x 109)/L, one patient developed a clinical picture of idiopathic thrombocytopenic purpura, and six patients maintained a platelet count greater than 20 x 10(9)/L at a median of 23 days (range 14 to 25 days) following stem cell infusion. This technique allows patients ineligible for autologous bone marrow transplantation due to unacceptable anesthetic risks, prior pelvic irradiation, or bone marrow metastases to receive marrow ablative therapy.

scholarly journals Application of hyperthermia to the treatment of human acute leukemia: purging human leukemic progenitor cells by heat

Blood ◽  
1986 ◽  
Vol 67 (3) ◽  
pp. 802-804 ◽  
Author(s):  
Y Moriyama ◽  
M Narita ◽  
K Sato ◽  
M Urushiyama ◽  
S Koyama ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Acute Leukemia ◽  
Progenitor Cells ◽  
Autologous Bone Marrow Transplantation ◽  
Leukemic Cell ◽  
Autologous Bone Marrow ◽  
Leukemic Cells ◽  
Neoplastic Disease ◽  
Myeloid Progenitor Cells

Abstract The application of hyperthermia to the treatment of neoplastic disease has focused on solid tumors. Since the hyperthermic sensitivity of human acute leukemia cells is not known, we have studied the in vitro response of human leukemic progenitor cells (L-CFU) to hyperthermia using a quantitative assay system for L-CFU. Human L-CFU were found to be more sensitive than committed normal myeloid progenitor cells to hyperthermic killing (41 to 42 degrees C). In addition, in the five acute myelogenous leukemic patients studied, it was shown that their leukemic progenitor cells--all types were studied according to the French-American-British diagnosis--were unable to form colonies when exposed to a temperature of 42 degrees C for 60 minutes, whereas the residual normal clones suppressed by the leukemic cell population were found to recover and to form more colonies in vitro as compared with untreated leukemic marrows. This strongly suggests that in vitro hyperthermia may selectively purge residual leukemic cells, especially L-CFU in stored remission bone marrow before autologous bone marrow transplantation.

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.

scholarly journals Application of hyperthermia to the treatment of human acute leukemia: purging human leukemic progenitor cells by heat

Blood ◽  
1986 ◽  
Vol 67 (3) ◽  
pp. 802-804
Author(s):  
Y Moriyama ◽  
M Narita ◽  
K Sato ◽  
M Urushiyama ◽  
S Koyama ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Acute Leukemia ◽  
Progenitor Cells ◽  
Autologous Bone Marrow Transplantation ◽  
Leukemic Cell ◽  
Autologous Bone Marrow ◽  
Leukemic Cells ◽  
Neoplastic Disease ◽  
Myeloid Progenitor Cells

The application of hyperthermia to the treatment of neoplastic disease has focused on solid tumors. Since the hyperthermic sensitivity of human acute leukemia cells is not known, we have studied the in vitro response of human leukemic progenitor cells (L-CFU) to hyperthermia using a quantitative assay system for L-CFU. Human L-CFU were found to be more sensitive than committed normal myeloid progenitor cells to hyperthermic killing (41 to 42 degrees C). In addition, in the five acute myelogenous leukemic patients studied, it was shown that their leukemic progenitor cells--all types were studied according to the French-American-British diagnosis--were unable to form colonies when exposed to a temperature of 42 degrees C for 60 minutes, whereas the residual normal clones suppressed by the leukemic cell population were found to recover and to form more colonies in vitro as compared with untreated leukemic marrows. This strongly suggests that in vitro hyperthermia may selectively purge residual leukemic cells, especially L-CFU in stored remission bone marrow before autologous bone marrow transplantation.

Sign in / Sign up

Export Citation Format

Share Document