Early identification and management of graft failure after unrelated cord blood transplantation

Abstract

Delayed hematologic recovery is common after unrelated donor umbilical cord blood transplants (UCBT). Clinically it is important to quickly differentiate slow engraftment from graft failure (GF). We report the engraftment data on 110 pediatric UCBT recipients. By day 28, 71 patients achieved an ANC 40.5 Â 10 9 per liter, and 6 others died early without recovery. Of the remaining 33 patients who were still neutropenic, 20 eventually attained donor myeloid recovery, 3 died of transplant-related complications or recurrent leukemia and 10 survived without donor-derived hematopoiesis. These patients received a second UCBT 33-95 days after the first transplant, after additional immunosuppression. One patient died early, the remaining nine patients were engrafted; eight demonstrated complete, and one mixed, donor chimerism (with subsequent graft loss). Acute GVHD developed in three, and chronic GVHD in six of the eight engrafted patients. Two patients developed EBV-lymphoproliferative disorder. Infections, especially viral, were common and protracted. Six of 10 patients are alive, 165-1375 (median 1147) days after second UCBT. Chimerism studies correlated with subsequent engraftment course. Any result showing o5% donor cells was associated with irreversible graft loss. In conclusion, early second UCBT after primary GF is a feasible treatment option. Chronic GVHD and viral reactivation are common post transplant.

Early peripheral blood and T-cell chimerism dynamics after umbilical cord blood transplantation supported with haploidentical cells

“…[19][20][21][22] After conventional allogeneic SCT, early detection of graft failure enables early salvage interventions such as manipulation of immunosuppressive therapy and/or donor lymphocyte infusion. 27,28 However, in the CB SCT setting, since additional cells are not available, once graft failure is detected, a second transplant has to be planned in most cases.…”

“…BM chimerism on day þ 30 of these cases showed a median of 100% of CB cells (range 75-100%). Median time to neutrophil engraftment in this group was 19 days (range [11][12][13][14][15][16][17][18][19][20][21][22][23][24][25][26][27][28][29].…”

“…With this objective, chimerism studies performed in the early post-transplant period have been shown to facilitate prediction of engraftment outcome in different allogeneic SCT settings including CB SCT. [19][20][21][22] This is especially true if chimerism is analyzed in different cell subsets. 23 More recently, chimerism studies performed on CD3 þ cells after double CB transplantation with reduced intensity conditioning have been shown to predict unit dominance.…”

“…With this objective, chimerism studies performed in the early post-transplant period have been shown to facilitate prediction of engraftment outcome in different allogeneic SCT settings including CB SCT. [19][20][21][22] This is especially …”

Are backup BM harvests worthwhile in unrelated donor allogeneic transplants?

“…After transplantation from unrelated donors (URDs), graft failure occurs rarely, but is more frequent after HLA-mismatched transplants, 1,2 T-cell depletion, 3 reduced intensity regimens and cord blood grafts. 4,5 Other factors that contribute to graft failure include minimal earlier treatment, low numbers of CD34 þ cells in the graft and drug-related toxicity. 6,7 Graft failure is life-threatening and usually results in infectious death.…”