Role of Total Body Irradiation in Conditioning for Bone Marrow Transplantation

Vriesendorp, Huibert M.; Bekkum, D. W. van

doi:10.1007/978-3-642-67319-1_30

Cited by 24 publications

(9 citation statements)

References 19 publications

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“…However, the extrapolated No was significantly lower than the most reliable estimates for the total number of rhesus monkey bone marrow cells, on which basis we had to assume that in the lower dose range of 1 to 5 Gy , hemopoietic reconstitution is mainly derived from a more radiosensitive cell type. In fact, such a cell type is perfectly in agreement with the LD50 for the untreated bone marrow syndrome and the Do value of 0.5-0.75 Gy reported earlier [3], which was indeed based on observations in the lower dose range of 1 to 5 Gy, and is also in agreement with the mouse studies summarized below. We concluded that, even following doses of TBI which approach lethality due to gastrointestinal damage, sufficient hemopoietic stem cells survived for ultimate hemopoietic reconstitution, be it at the expense of a prolonged period of profound pancytopenia in addition to longstanding immunodeficiency.…”

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confidence: 92%

“…Vriesendorp and Van Bekkum [3] arrived at Do values between 0.5 and 0.7 .5 Gy. Although this approach may still be valid to characterize the radiation sensitivity of hemopoietic cells required for rescue from radiation-induced bone marrow failure in an untreated patient, more recent evidence has accumulated to demonstrate that the heterogeneity of immature hemopoietic cells is also reflected by a heterogeneity in radiation sensitivity with practical consequences for the treatment of radiation accident victims.…”

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Chapter 6: Cell and cell system responses: Heterogeneity of radiation sensitivity of hemopoietic stem cell subsets

Wagemaker¹

1995

Stem Cells

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Immature hemopoietic cells are heterogeneous with respect to repopulating capacity following exposure to ionizing radiation, growth factor receptor and surface marker phenotype as well as cycling state. In the present paper, the evidence from studies in subhuman primates and mice is reviewed, which demonstrates that the heterogeneity of immature stem cells is also reflected by a differential sensitivity to radiation, the most immature stem cells with long-term repopulating capacity being less sensitive to radiation than assumed on the basis of 50% lethal dose (LD50) data, and the radiation sensitivity of immature hemopoietic cells measured by the spleen-colony test. In addition, these immature cells appear to have a considerable repair capacity. These findings have a direct bearing on future strategies for the treatment of patients after accidental exposure to ionizing radiation, either by transplantation of (subsets of) stem cells or by administration of a specific combination of hemopoietic growth factors.

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confidence: 92%

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confidence: 96%

Chapter 6: Cell and cell system responses: Heterogeneity of radiation sensitivity of hemopoietic stem cell subsets

Wagemaker¹

1995

Stem Cells

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“…14,27 Unfortunately, this strategy cannot be applied to humans due to the limited number of hematopoietic cells that can be harvested using the current clinically available procedures. It is widely accepted that myeloablation facilitates engraftment of fresh and/or transduced syngeneic hematopoietic cells in most transplantation models, [30][31][32][33][34] and that ex vivo transduction of the graft impairs the repopulating ability of the graft. However, whether there is a threshold level of engraftment of transduced cells for tolerance induction still needs to be elucidated.…”

Section: In the Bm Of The Recipient Mice 5 Months After Transplanmentioning

confidence: 99%

Myeloablation enhances engraftment of transduced murine hematopoietic cells, but does not influence long-term expression of the transgene

et al. 2002

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“…The LD50 for TBI of dogs is lower than in most other experimental animals. A model explaining this result has been presented in a previous paper (Vriesendorp & van Bekkum 1980a). The LD50 for the GI syndrome in dogs is lower than that in rodents and rhesus monkeys.…”

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confidence: 71%

“…The optimal BM cell number is the one that guarantees a timely reoccurrence of hemopoietic end cells and does not increase the risks of GvHD. Extrapolations from animal studies suggest that for humans this number is approximately 2 x 1O8.kg-' (Vriesendorp et al 1980a).…”

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confidence: 98%

Factors controlling the engraftment of transplanted dog bone marrow cells

Vriesendorp¹,

Klapwyk²,

Heidt³

et al. 1982

Tissue Antigens

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The LD50 of total body irradiation (TBI) for the bone marrow (BM) syndrome and the gastrointestinal (GI) syndrome was determined in dogs as 3.7 Gy, and 8.5 Gy respectively. Five Gy TBI was adequate conditioning for BM cells of littermate donors identical for the major histocompatibility complex (MHC). The maximum tolerated TBI (about 7.5 Gy) caused more side effects than 5.0 Gy TBI and was insufficient for engraftment of realistic numbers of BM cells of MHC mismatched donors. In autologous and MHC matched transplants, the rate of hemopoietic recovery correlated with the number of BM cells given. Approximately 2 x lo7 autologous and 1 x lo8 MHC identical BM cells.kg-' were needed for radiation protection. Platelet recovery was significantly more rapid in allogeneic combinations in comparison to autologous transplants. Low numbers of autologous cryopreserved bone marrow cells were as effective as fresh bone marrow cells in rescuing animals after lethal TBI. Other factors that influence BM cell engraftment were confirmed (prior sensitization of the recipient, donor selection) or identified (purification of BM cells on density gradient and selective gastrointestinal decontamination of the recipient). Consistent engraftment of gradient separated, MHC identical, BM cells was found after conditioning with two fractions of 6.0 Gy TBI, separated by 72 h. One MHC haplotype mismatched marrow did engraft after two TBI fractions of 6.0 Gy. Engraftment no longer occurred with gradient purified bone marrow cells from this type of donor. Late effects of TBI were early greying in all animals, and secondary uterinc inertia in female dogs after 7.5 Gy TBI. Fertility in males or females was not changed by radiation. An increased incidence of pancreas fibrosis was noted in dogs receiving two fractions of 6.0 Gy TBI.

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Role of Total Body Irradiation in Conditioning for Bone Marrow Transplantation

Cited by 24 publications

References 19 publications

Chapter 6: Cell and cell system responses: Heterogeneity of radiation sensitivity of hemopoietic stem cell subsets

Chapter 6: Cell and cell system responses: Heterogeneity of radiation sensitivity of hemopoietic stem cell subsets

Myeloablation enhances engraftment of transduced murine hematopoietic cells, but does not influence long-term expression of the transgene

Factors controlling the engraftment of transplanted dog bone marrow cells

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