Nonmyeloablative conditioning with 200 cGy total body irradiation (TBI) prior to matched littermate allogeneic hematopoietic stem cell transplantation (HSCT) in dogs with canine leukocyte adhesion deficiency results in higher levels of engraftment and donor chimerism compared to busulfan alone

Renal dysfunction because of radiation exposure was recognized decades ago. The incidence declined when more effective chemotherapeutic agents became available. However, there appears to be a resurgence with the advent of total body irradiation used prior to hematopoietic stem cell transplantation. Several chemotherapeutic drugs used prior to total body irradiation have some ionizing radiation potentiating effects. Chronic kidney disease that occurs after hematopoietic stem cell transplantation is known to occur due to nephrotoxicity from medications, graft-versus-host disease, and the currently under-recognized radiation exposure. The clinical features vary depending on the dose of radiation and the volume of single or bilateral kidneys exposed. The usual symptoms of fatigue, edema, anemia, malignant hypertension, azotemia, and shortness of breath appear in 6–12 months of exposure. Since this is an under-recognized entity, there are no large controlled trials to guide therapy. This review highlights some of the experimental data that have shown some promising results for treatment. There is need for further studies on the current incidence and prevalence and clinical trials to guide treatment, based on the experimental data available.

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Reproductive capability in dogs with canine leukocyte adhesion deficiency treated with nonmyeloablative conditioning prior to allogeneic hematopoietic stem cell transplantation

Blood ◽

10.1182/blood-2006-02-005645 ◽

2006 ◽

Vol 108 (5) ◽

pp. 1767-1769 ◽

Cited By ~ 8

Author(s):

Tanya H. Burkholder ◽

Lyn Colenda ◽

Laura M. Tuschong ◽

Matthew F. Starost ◽

Thomas R. Bauer ◽

...

Keyword(s):

Stem Cell ◽

Hematopoietic Stem Cell Transplantation ◽

Stem Cell Transplantation ◽

Cell Transplantation ◽

Hematopoietic Stem Cell ◽

Leukocyte Adhesion ◽

Reproductive Function ◽

Leukocyte Adhesion Deficiency ◽

Hematopoietic Stem ◽

Conditioning Regimens

Nonmyeloablative conditioning regimens are increasingly replacing myeolablative conditioning prior to allogeneic hematopoietic stem cell transplantation (SCT). The recent advent of these conditioning regimens has limited the assessment of the long-term effects of this treatment, including analysis of reproductive function. To address the question of reproductive function after nonmyeloablative transplantation, we analyzed a cohort of young dogs with the genetic disease canine leukocyte adhesion deficiency that were treated with a nonmyeloablative dose of 200 cGy total body irradiation followed by matched-littermate SCT. Five males and 5 females entered puberty; all 5 males and 4 females subsequently sired or delivered litters following transplantation. We demonstrate that fertility is intact and dogs have uncomplicated parturitions following nonmyeloablative conditioning for SCT. These results are encouraging for children and adults of childbearing age who receive similar conditioning regimens prior to allogeneic transplantation.

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