A Study on the Dose Distribution for Total Body Irradiation using Co-60 Teletherapy Unit

To evaluate the characteristics of cataracts following hematopoietic stem cell transplantation (HSCT), 561 patients without any ocular complications before HSCT were reviewed. Ocular complications occurred in 196 patients (34.9%). Cataract was diagnosed in 45 of 561 patients. The 10-year estimated cataract incidence was 14%. The median onset time was 498 days after transplant (range, 38-4,535 days). The onset of cataracts was later than that of other ocular complications. Phacoemulsification was performed in 13 patients (29%) at a median of 1,028 days after HSCT (range, 375-4,549 days). In 6 of 13 patients (46%) who underwent cataract surgery, visual acuities gradually deteriorated because of the development of posterior capsule opacification. YAG (yttrium-aluminum-garnet) laser posterior capsulotomy successfully recovered their sight without any sequelae. A multivariate analysis revealed that age, acute and chronic graft versus host disease (GVHD), and systemic infection were significant risk factors for cataract, whereas neither steroid nor total body irradiation (TBI)-containing regimens affected the development of cataract. Our results showed that the clinical outcomes of cataract after HSCT are favorable and comparable to those in the general population. Hyperfractionated TBI with eye shielding may be effective for the prevention of cataract.

Addition of low dose total body irradiation to fludarabine melphalan reduced intensity conditioning is feasible, tolerable, and may improve outcomes in patients with high-risk acute myeloid leukaemia and other high risk myeloid malignancies.

Conditioning regimens using growth factors prior to low dose tbi enhance engraftment of murine stem cells after bone marrow transplantations

Quality of Life and Comorbidities of Adult Survivors of Allogeneic Hematopoietic Cell Transplant Versus Their Siblings

Slavin et al. in [1976], were the first to found that rejection of skin and heart allograft was greatly delayed in rodents treated with Total Lymphoid Irradiation (TLI). Since 1980, the immunosupression of TLI has been applied in transplants and autoimmune diseases. However, the development of immunosuppressive drugs decreased the use of radiotherapy for immunosuppressive finality except for the use of total body irradiation (TBI) or TLI as myeloablative treatment before bone marrow transplantation The mechanism by which TLI-treated patients have a graft prolongation is not entirely understood. During many years of its use many changes has been observed specially in lymphocytes counts. The majority of the studies, however, were done without modern techniques to characterize the fate of different subtypes of lymphocytes and is difficult to compare the results. The majority of the studies has been done in vitro and in regimes using TBI and bone marrow transplants. There is some evidence that suppressor T-cells might be involved in the long term maintenance of allografts in these patients [Gray et al, 1989]. TLI provokes a more pronounced impairment of T-dependent immunological functions, as measured with phytohemaglutinin(PHA), concanavalin A(Con A), and pokeveedinduced (PWM) blastogenesis than does conventional immunosuppression. The more profound changes in the balance between T helper and T suppressor cells after TLI are also associated with a more pronounced suppressor cell activity, as measured with different functional suppressor cell assays. [Fergunson et al, 1981; Waer et al, 1987]. The TLI seems to produce an “amnesic state” and the autoantigens cannot be recognized by the host anymore. In the past, radiation therapy had traditionally been viewed as immunosuppressive (Cole, 1986; James et al., 1989; Wasserman et al., 1989). Lymphocyte radiosensitivity is well established and remains the dominant explanation for this effect. However, substantial evidence suggests more varied effects of radiation on the immune system, prompting the recharacterization of radiation as ‘immunomodulatory’ rather than immunosuppressive (McBride et al., 2004). Ionising radiation induces diverse effects on cell survival, apoptosis, proliferation and differentiation depending on the dosage and target cell (Jonathan et al. 1999). High dose of radiation often results in massive DNA damage that involves double-strand breaks and subsequent cell death. Low dose of irradiation induces reactive oxygen species (ROS) and the activation of specific intracellular signaling pathways and transcription factors leading to proliferation and differentiation of target cells (Kasid et al. 1996, Lander et al. 1997, Finkel 1998). Therefore, irradiation can modulate immune response via its variable effects on immune cell survival and differentiation (Shankar et al. 1999, Rho et al. 2004, Liu 2007, Shan et al.2007).

When BALB/c mice received 17 daily fractions of 2 Gy each of total lymphoid irradiation (TLI, total dose 34 Gy) and 30 X 10(6) C57 B1 bone marrow cells (BM) on the day after the last fraction, stable bone marrow chimerism without signs of graft-vs-host disease (GVHD) was obtained in 84% of the animals. On the contrary, in BALB/c mice receiving only seven fractions of TLI (total dose 14 Gy), all bone marrow grafts were rejected. When the last two fractions of a 14-Gy TLI course were given without shielding the extra lymphatic tissues (combined total lymphoid + total body irradiation, TLBI), chimerism could be induced in 53% of the animals. When this 14-Gy TLBI schedule was used, it was even possible to administer four fractions per day (multiple fractions per day schedule, MFD), thus reducing the overall treatment time to 2 consecutive days. After this concentrated form of TLBI, chimerism was detected in 35% of the animals. As in the 34-Gy TLI schedule, graft-vs-host reaction could not be prevented in the 14-Gy TLBI schedule when spleen lymphocytes (10 X 10(6) were added to the BM inoculum. Leucopenia or suppression of the phytohaemagglutinin (PHA)-induced blastogenesis could not predict which schedule would result in a successful allogeneic bone marrow take. Suppressor cells of the mixed lymphocyte reaction, on the other hand, were only found in the spleen of BALB/c mice treated with the TLI or TLBI schedules, which also resulted in stable bone marrow chimerism.

Low-dose total body irradiation causes clonal fluctuation of primate hematopoietic stem and progenitor cells

Unrelated Donor Transplants for Older AML Patients Using a Low Dose TBI Containing Regimen Are As Efficacious As Related Donor Transplants, and Exhibit Favorable Outcomes for Intermediate Risk Disease.

The evolution of Vbeta6-expressing C3H (H2k, Thy 1.2, Mls a-) lymphocytes was investigated in C3H recipients mice pretreated with total body irradiation (TBI) or total lymphoid irradiation (TLI) and infusion of AKR (H2k, Thy 1.1, Mls a+) cells. After TBI (9.5 Gy) all Vbeta6+ Thy 1.2 (C3H) cells, which are capable of reacting against the Mls a antigen that like expressed by AKR mice, were deleted in the thymus and the periphery in stable bone marrow (BM) chimeras obtained by infusion of 5 x 10(6) T-cell-depleted (TCD) AKR BM cells. When, in the opposite combination, 30 x 10(6) C3H spleen cells were infused into TBI-treated AKR cells, all animals developed graft-versus-host disease (GVHD) with no clonal deletion and in contrast, showed an increase in Vbeta6+ C3H cells. After injection of 30 x 10(6) AKR BM cells into TLI-treated C3H mice no C3H cells were detected in the thymus and only a small percentage in the periphery. Within these C3H cells Vbeta6+ cells were only partially deleted and anergized as they did not respond in vitro after stimulation with Mls a+ AKR cells or anti-Vbeta6 mAb. Cells suppressing anti-Mls a-reacting C3H cells were not found. After injection of 15 x 10(6) AKR cells more C3H cells were found in the thymus, but only a minority of Vbeta6+ cells persisted in the periphery of these animals. In conclusion in TBI-prepared chimeras only clonal deletion occurred, whereas in TLI-prepared chimeras both clonal deletion and anergy occurred in maintaining tolerance.

A Phase I Study of Hypofractionated Tailored Total Marrow or Total Lymphoid Irradiation with Helical Tomotherapy Plus Chemotherapy As a Conditioning Regimen for Autologous Stem Cell Transplantation

Posttransplantation cyclophosphamide facilitates engraftment of major histocompatibility complex-identical allogeneic marrow in mice conditioned with low-dose total body irradiation.

Between September 78 and May 81, 13 adults (mean age 27± 7 years) with acute myeloid leukemia (AML) in 1st remission (n=11) or chronic myeloid leukemia (CML) in 2nd chronic phase, were given donor buffy coat cells, Cyclophosphamide (60 mg/kg×2), and low dose total body irradiation (TBI) as conditioning regimen for allogeneic bone marrow transplantation (BMT) from an HLA identical sibling donor.

Allogeneic Stem Cell Transplantation (SCT) Using Rabbit-ATG (Thymoglobulin®) and Low Dose Total Body Irradiation (TBI): Favorable Outcomes with Unrelated Donors (URD).

Allogeneic Hematopoietic Stem Cell Transplantation in HIV-Positive Patients with Malignant and Non-Malignant Disorders: A Report from the Center for International Blood and Marrow Transplant Research (CIBMTR).

Total marrow and lymphoid irradiation (2000 cGy) together with cyclophosphamide and etoposide prior to allogeneic hematopoietic cell transplantation is an effective regimen for Relapsed/Refractory leukemia, with low non-relapse mortality