Are Back-Up Bone Marrow Harvests of Value in Unrelated Donor Allogeneic Transplants?.
Authors: Stotler Christy , Copelan Edward , Sobecks Ronald , Rybicki Lisa , Dean Robert , Andresen Steven , Pohlman Brad , Sweetenham John William , Brown Stacey , Kalaycio Matt , Curtis Julie , Sands Karen , Serafin Mary , Kosar Jennifer , Bolwell Brian 
Published: October 2019

In June 2007 four members of the University of Michigan Cardiothoracic transplant team died in a plane crash while transporting organs to an expectant transplant recipient. Matched Unrelated Donor Stem Cell transplants (MUDs) require that patients receive the preparative regimen before the hematopoeitic stem cells are transported. Our transplant program performs a “back-up” autologous harvest prior to administration of the conditioning regimen for use if the donor graft fails to arrive or if graft failure occurs. However, this practice is not uniform and insurers sometimes balk at payment. To evaluate the value of their routine collection, we reviewed the results of our center’s use of back-up marrows. 215 MUD transplants were performed at CCF from 1/95 to 12/05 and 146 recipients underwent back-up marrow collection. All recipients of adult MUD or Cord Blood transplants with hematologic malignancies in complete remission were harvested. Of 146 back-up marrows harvested, 15 patients (10%) had their back-up harvest infused. All 15 patients received their rescue marrow infusion for graft failure (adult MUD, n=12; Cord, n=3) 0.7–7.6 (median 1.1) months after the original transplant. Seven of the 15 (46%) patients had undergone full molecular matching, the other 8 (54%) patients being matched by serology for class I antigens and DNA typing for class II antigens. 9 patients were 6/6 serologic or molecular matches, 3 patients were 5/6 matches, and the 3 cord transplants were 4–5/6 matches. Deteriorating clinical status and a need for rapid engraftment was the rationale for infusion of autologous back-up marrow, as opposed to seeking additional donor cells (which potentially takes several weeks). Five patients (33%) are alive and in complete remission 14.6 to 137 (median 91) months from back-up infusion. Of these, two were bridged to a second MUD transplant. These two patients are alive and well at days 4200 and 1950 respectively. The other three have shown surprisingly durable disease free survival without repeat allogeneic transplant.

Survivors Following Rescue Autologous Stem Cell Infusion Patient No. Primary Disease Transplant Material - all MUD Day of rescue infusion HLA typing of 1st transplant Second transplant Outcome 1 CML BM +29 Serologic 6/6 Yes (+560) Alive last f/u (+4200) 2 CML BM +33 Serologic 5/6 No Alive last f/u (+3363) 3 NHL BM +62 Serologic 8/8 No Alive last f/u (+2833) 4 AML Adult PBSC +230 Molecular 8/8 Yes (+1581) Alive and well (+1950) 5 AML Cord +38 Molecular 5/6 No Alive last f/u (+482)

In total, 5 patients went on to a second transplant, all from adult MUD donors. Three patients died following second transplant - two from relapse and the 3rd from ARDS. Ten patients died following back-up infusion: 4 (36%) from relapse, 5 (54%) from infections and 1 from graft failure before rescue cells could engraft. Within this group, patients lived a mean of 114.5 (4–357) days from autologous rescue. Five patients were discharged from the hospital and lived a mean of 7.1 (1–12) months from discharge. In conclusion, a rescue autograft following graft failure may allow for rapid hematopoeitic recovery providing an opportunity for a second allogeneic transplant if another donor is available. In some cases it can directly result in durable remission. This procedure has saved the lives of 5 patients and should be more widely employed.