scholarly journals Syngeneic and allogeneic bone marrow engraftment after total body irradiation: dependence on dose, dose rate, and fractionation

Blood ◽  
1991 ◽  
Vol 77 (3) ◽  
pp. 661-669 ◽  
Author(s):  
JD Down ◽  
NJ Tarbell ◽  
HD Thames ◽  
PM Mauch
Keyword(s):  
Bone Marrow ◽  
Stem Cell ◽  
Radiation Dose ◽  
Dose Rate ◽  
Dose Response ◽  
Total Body Irradiation ◽  
Low Dose ◽  
Allogeneic Bone ◽  
Low Dose Rate ◽  
Total Body

Murine bone marrow chimera models were used to assess the efficacy of host total body irradiation (TBI) given at different doses, dose rates, and fractionation schemes in providing for engraftment of syngeneic and allogeneic bone marrow. B6-Hbbd congenic and LP mice, respectively, were used as donors (10(7) bone marrow cells) for syngeneic and allogenic (H-2 compatible) transplantation in standard B6 recipients. Stable marrow chimerism was determined from host and donor stem cell- derived hemoglobin phenotypes (Hbbs and Hbbd) on gel electrophoresis at 3 months posttransplant. Partial engraftment of syngeneic marrow was seen at single doses as low as 2 Gy, with the donor component increasing steadily with increasing TBI dose to a level of 100% at 7 Gy. Immunologic resistance of the host appeared to prevent allogeneic engraftment until 5.5 Gy. A very steep radiation dose response was then observed so that the level of chimerism with 6 Gy and above became comparable with syngeneic engraftment. Low dose rate (5 cGy minute-1) and fractionated TBI required higher total doses for equivalent engraftment (radiation dose-sparing) in both syngeneic and allogenic bone marrow transplantation. This displacement in the dose-response curve on fractionation was seen with interfraction intervals of 3 and 6 hours. A further dose-sparing effect was observed on extending the interval to 18 and 24 hours, but only for allogeneic transplantation, and may therefore be related to recovery of immune-mediated graft resistance. The involvement of multiple target cell populations in determining allogenic engraftment rendered the application of the linear-quadratic model for radiation cell survival problematic in this case. The recovery in dose when low dose rate and 6-hour interfraction intervals were applied in either syngeneic or allogeneic BMT is consistent with appreciable sub-lethal damage repair in the primitive self-renewing stem cell population of the host marrow. These results contrast with the poor repair capacity of the 11-day spleen colony- forming units (CFUs) population after fractionated irradiation and support the notion that ablation of early stem cells in the pre-CFUs compartment is essential for long-term marrow engraftment.

scholarly journals Syngeneic and allogeneic bone marrow engraftment after total body irradiation: dependence on dose, dose rate, and fractionation

Blood ◽  
1991 ◽  
Vol 77 (3) ◽  
pp. 661-669 ◽  
Author(s):  
JD Down ◽  
NJ Tarbell ◽  
HD Thames ◽  
PM Mauch
Keyword(s):  
Bone Marrow ◽  
Stem Cell ◽  
Radiation Dose ◽  
Dose Rate ◽  
Dose Response ◽  
Total Body Irradiation ◽  
Low Dose ◽  
Allogeneic Bone ◽  
Low Dose Rate ◽  
Total Body

Abstract Murine bone marrow chimera models were used to assess the efficacy of host total body irradiation (TBI) given at different doses, dose rates, and fractionation schemes in providing for engraftment of syngeneic and allogeneic bone marrow. B6-Hbbd congenic and LP mice, respectively, were used as donors (10(7) bone marrow cells) for syngeneic and allogenic (H-2 compatible) transplantation in standard B6 recipients. Stable marrow chimerism was determined from host and donor stem cell- derived hemoglobin phenotypes (Hbbs and Hbbd) on gel electrophoresis at 3 months posttransplant. Partial engraftment of syngeneic marrow was seen at single doses as low as 2 Gy, with the donor component increasing steadily with increasing TBI dose to a level of 100% at 7 Gy. Immunologic resistance of the host appeared to prevent allogeneic engraftment until 5.5 Gy. A very steep radiation dose response was then observed so that the level of chimerism with 6 Gy and above became comparable with syngeneic engraftment. Low dose rate (5 cGy minute-1) and fractionated TBI required higher total doses for equivalent engraftment (radiation dose-sparing) in both syngeneic and allogenic bone marrow transplantation. This displacement in the dose-response curve on fractionation was seen with interfraction intervals of 3 and 6 hours. A further dose-sparing effect was observed on extending the interval to 18 and 24 hours, but only for allogeneic transplantation, and may therefore be related to recovery of immune-mediated graft resistance. The involvement of multiple target cell populations in determining allogenic engraftment rendered the application of the linear-quadratic model for radiation cell survival problematic in this case. The recovery in dose when low dose rate and 6-hour interfraction intervals were applied in either syngeneic or allogeneic BMT is consistent with appreciable sub-lethal damage repair in the primitive self-renewing stem cell population of the host marrow. These results contrast with the poor repair capacity of the 11-day spleen colony- forming units (CFUs) population after fractionated irradiation and support the notion that ablation of early stem cells in the pre-CFUs compartment is essential for long-term marrow engraftment.

SU-E-T-320: Low Dose Rate Pediatric Total Body Irradiation (TBI) Using TrueBeam

2013 ◽  
Vol 40 (6Part15) ◽  
pp. 278-278 ◽  
Author(s):  
N Knutson ◽  
S Yaddanapudi ◽  
H Li
Keyword(s):  
Dose Rate ◽  
Total Body Irradiation ◽  
Low Dose ◽  
Low Dose Rate ◽  
Total Body

Allogeneic bone marrow transplantation in acute nonlymphocytic leukemia: a pilot study

Blood ◽  
1982 ◽  
Vol 60 (2) ◽  
pp. 400-403 ◽  
Author(s):  
JH Kersey ◽  
NK Ramsay ◽  
T Kim ◽  
P McGlave ◽  
W Krivit ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Young Adults ◽  
Dose Rate ◽  
Total Body Irradiation ◽  
High Dose ◽  
Allogeneic Bone ◽  
Acute Nonlymphocytic Leukemia ◽  
Free Survival ◽  
Children And Young Adults ◽  
Total Body

Abstract The objective of the current study, initiated in 1976, was to improve upon the high relapse rate and subsequent mortality in children and young adults with acute nonlymphocytic leukemia (ANLL). Seventeen patients, ages 6--28, with ANLL in first bone marrow remission, received cyclophosphamide and total body irradiation using a radiation scheme of 750 rad (7.5 Gy) total dose, delivered at a dose rate of 26 rad (26 cGy) per minute. Allogeneic marrow from HLA-matched sibling donors was followed by prophylactic therapy or graft-versus-host disease (GVHD). Median follow-up of the entire group is 20+ mo; survivors have been followed for a minimum of 14+ mo. Interstitial pneumonitis was observed in 6% of patients, and GVHD was observed in 29%. Seventy percent of patients are alive and in complete continuous remission. Two patients have relapsed (at 7 and 24 mo). Actuarial relapse-free survival is 76% at 1 yr and 64% at 5 yr. Quality of life in this disease-free survivors is excellent; all patients are free of active GVHD, receive no maintenance chemotherapy, and have high Karnofsky performances scores. High dose rate total body irradiation plus cyclophosphamide followed by allogeneic BMT may provide an opportunity for long-term complication-free survival in a substantial proportion of children and young adults with ANLL.

scholarly journals Busulfan and total body irradiation as antihematopoietic stem cell agents in the preparation of patients with congenital bone marrow disorders for allogenic bone marrow transplantation

Blood ◽  
1984 ◽  
Vol 64 (4) ◽  
pp. 852-857
Author(s):  
R Parkman ◽  
JM Rappeport ◽  
S Hellman ◽  
J Lipton ◽  
B Smith ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Stem Cell ◽  
Bone Marrow Transplantation ◽  
Total Body Irradiation ◽  
Interstitial Pneumonitis ◽  
Marrow Transplantation ◽  
Allogeneic Bone ◽  
Hematopoietic Stem ◽  
Total Body ◽  
Bone Marrow Disorders

The capacity of busulfan and total body irradiation to ablate hematopoietic stem cells as preparation for the allogeneic bone marrow transplantation of patients with congenital bone marrow disorders was studied. Fourteen patients received 18 transplants; busulfan was used in the preparatory regimen of eight transplants and total body irradiation in the regimens of six transplants. Sustained hematopoietic ablation was achieved in six of eight patients prepared with busulfan and in all six patients prepared with total body irradiation. Three patients prepared with total body irradiation died with idiopathic interstitial pneumonitis, whereas no patients receiving busulfan developed interstitial pneumonitis. The optimal antihematopoietic stem cell agent to be used for the preparation of patients with congenital bone marrow disorder for bone marrow transplantation is not certain.

Chapter 6: Cell and cell system responses: Response of hemopoiesis in dogs to continuous low dose rate total body irradiation

Stem Cells ◽  
1995 ◽  
Vol 13 (S1) ◽  
pp. 261-267 ◽  
Author(s):  
Wilhelm Nothdurft ◽  
Theodor M. Fliedner ◽  
Thomas E. Fritz ◽  
Thomas M. Seed
Keyword(s):  
Dose Rate ◽  
Total Body Irradiation ◽  
Low Dose ◽  
Cell System ◽  
Low Dose Rate ◽  
Total Body
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