Adult Mismatched Umbilical Cord Blood Transplant Is Feasible in a Community Setting for an Unselected Group of High Risk Patients.

Conflicting results has been found on how the size of a transplant program affected the clinical outcome of hematopoietic stem cell transplant (HSCT). Some insurance carriers demand their clients to only receive HSCT in large centers, even if the service is available locally and the patients have to travel a long distance away from their home to receive the service at the approved program. Amarillo, Texas is 350 miles from Dallas and 600 miles from Houston. The HSCT program was established in Dec 2001. 18–25 transplants (autologous, allogeneic and umbilical cord blood (UCB) transplants) are performed a year. To determine whether a justification could be made to offer HSCT in a program that is small, new and community-based, we have analyzed the outcome of the adult mismatched umbilical cord blood transplants (UBCT) carried out on an unselected group of patients needing HSCT but without a matched sibling donor in our center in the last five years.

Thirteen patients (8 males and 5 females) have undergone unrelated mismatched UBCT. The median age was high at 54 years (range 17 to 78). Four patients received reduced intensity conditioning regimen with Flu/Mel and 9 patients received the myelo-ablative regimen with Bu/Cy. Four patients received two units and nine single unit of umbilical cord blood. The diagnosis were: CML in CP1 (1), CML in blast crisis (2), HD relapsed within three months after autologous transplant (1), SAA (2), refractory CLL (1), ALL with multiple relapses (1), AML in CR3 (1), untreated secondary AML (2), primary refractory AML (1) and secondary AML in CR1 (1). Five patients received UCB units that were 1 antigen mismatch, 4 patients 2 antigen mismatches and 4 patients 3 antigen mismatches. GVHD prophylaxis in all cases consisted of cyclosporine A and methylprednisone.

This is a group of mainly very high risk older patients. Not unexpectedly, early mortality rate was high. Death within 28 days of transplant occurred in 2 patients due to toxicity. Death within 100 days of transplant occurred in 8/13 (61.5%) patients. All the deaths occurred due to either infection or toxicity, except in one patient (age 67 years) who died due to a thrombotic stroke. Death due to disease relapse occurred in another patient 5 months after transplant for CML in blast crisis. Engraftment was documented in 9 patients. Despite the high antigen mismatches and the age of the patients, Grade I – II GVHD occurred in 7 patients and Grade III – IV in only 2 patients.

With a maximum follow-up of 49 months, 4/13 (30%) patients are alive disease-free: 49+ months (age 45 years, one DRB1 mismatch), 22+ months (25 years, two antigen mismatches), 15+ months (48 years, three antigen mismatches) and 4+ months (54 years, three antigen mismatches). These results, in a group of very high risk unselected older patients in a community setting, are extremely encouraging and are comparable to those reported on younger groups of patients.

Conclusions:

1. Adult mismatched UBCT is feasible in a small program in a community setting;

2. Patients >45 years may benefit from UBCT, even in the setting of multiple antigen mismatches;

3. Patient selection should reduce early death and improve survival;

4. Insurance companies should not deny patients to have transplant in their local program based on the size of the program.