Primary Graft Failure, Secondary Graft Failure
Conditions
Keywords
Hematopoietic stem cell transplant
Brief summary
This is a guideline for the treatment of graft failure after hematopoietic stem cell transplant (HSCT). This regimen, consisting of cyclophosphamide and fludarabine with low dose total body irradiation (TBI) is designed to promote donor engraftment by day 42 after initial graft failure. The graft will consist of bone marrow or G-CSF mobilized peripheral blood from a haploidentical related donor. The source of stem cells will be determined by the transplant team based on factors such as patient's age, medical history, donor availability and will be according to the current University of Minnesota Blood and Marrow Transplantation Program selection guidelines.
Interventions
DRUGCyclophosphamide
Cyclophosphamide 14.5 mg/kg IV over 1-2 hours given on days -6 and -5 from transplant. And Cyclophosphamide 50 mg/kg IV over 2 hours given on days +3 and +4 from transplant.
RADIATIONTotal Body Irradiation
TBI 200cGy in a single fraction on day -1 from transplant.
BIOLOGICALHematopoietic stem cell infusion
Hematopoietic stem cell infusion given on day 0.
DRUGFludarabine
Fludarabine 30 mg/m2 IV over 1 hour given on days -6 through -2 of transplant.
Sponsors
Masonic Cancer Center, University of Minnesota
Study design
Observational model
COHORT
Time perspective
PROSPECTIVE
Eligibility
Sex/Gender
ALL
Healthy volunteers
No
Inclusion criteria
* Patients with primary or secondary graft failure, as defined below, may receive a second transplant: * Primary graft failure is defined as not achieving an ANC ≥0.5x10\^9/L for three consecutive days by day 35 - 42 following the first transplant. * Secondary graft failure is defined as achieving an ANC ≥0.5x10\^9/L for three consecutive days by day 35 - 42, but subsequently drops below 0.5x10\^9/L without recovery. * Loss of chimerism is defined as achieving an ANC ≥0.5x10\^9/L for three consecutive, but with less than 10% CD15+ donor cells in the marrow or peripheral blood. * Recipients should have acceptable organ function defined as: * Renal: creatinine \< 2.0 (adults) and creatinine clearance \> 30. For creatinine clearance \< 70, consultation with a BMT pharmacist is necessary for chemotherapy dose adjustments. * Hepatic: bilirubin, AST/ALT, ALP \< 10 x upper limit of normal * Cardiac: left ventricular ejection fraction \> 40%
Exclusion criteria
* Uncontrolled infection at the time of transplant. * Patients with Fanconi Anemia or other DNA breakage syndromes.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Rate of donor engraftment | day 42 | Rate of sustained donor engraftment at day 42 post this transplant. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Rate of treatment related mortality | day 100 | Rate of treatment related mortality (TRM) at day 100 |
| Rate of survival | Day 100 | Rate of survival by day 100. |
| Incidence of acute graft-versus-host disease | Day 100 | Incidence of acute graft-versus-host disease by day 100 |
| Incidence of chronic graft-versus-host disease | 1 year | Incidence of chronic graft-versus-host disease at 1 year. |
Countries
United States
Contacts
Primary ContactTimothy Krepski
Outcome results
None listed