Predictors of Response in Patients Receiving CD34-Selected Stem Cell Infusions without Conditioning to Correct Graft Failure Following Allogeneic Stem Cell Transplantation

• Published in: Blood 2018-11, Vol.132 (Supplement 1), p.204-204
• Main Authors: Cuadrado, Maria del Mar, Lowdell, Mark W., Ings, Stuart, Watts, Michael J., Szydlo, Richard, Anthias, Chloe, Madrigal, J. Alejandro, Kottaridis, Panagiotis, Carpenter, Ben, Hough, Rachael, Peggs, Karl, Thomson, Kirsty, Morris, Emma, Chakraverty, Ronjon
• Format: Article
• Language: English
• ISSN: 0006-4971; 1528-0020
• DOI: 10.1182/blood-2018-99-115054

▪ Introduction: Graft failure (GF) is an infrequent but serious complication of following matched related or unrelated donor peripheral blood stem cell transplantation. Although infusion of CD34+-selected stem cells without additional conditioning is currently one strategy to treat this complication, few studies have reported predictors of response. Methods: We report the outcome of consecutive patients identified at two UK transplant centres between 1999 and 2017 who had primary or secondary GF after an allogeneic peripheral blood stem cell transplant and who underwent a CD34+ selected stem cell infusion without further conditioning. GF was confirmed by chimerism, bone marrow examination and exclusion of relapsed disease. Primary GF was defined by failure to ever achieve count recovery in one or more lineages (neutrophils >0.5x109/L, untransfused platelets >20 x109/L and untransfused Hb >8 g/L) post transplantation. Secondary GF was defined by loss of counts after the initial achievement of engraftment. A complete response (CR) was defined as haematological improvement (HI) in all cell lines (Hb>8g/L, platelets > 30x109/L and neutrophils > 1.5x109/L). A partial response (PR) was defined as HI within the first 30 days but not in all cell lineages. Responses were categorized as early (30 days); in the latter case, the role of the CD34+ infusion in count recovery was not known. Results: We identified 62 patients with GF, male:female 35:27, with a median age of 43 years (range, 10-66). Fifty-six patients (90%) had had reduced intensity conditioning. Median follow up was 6.4 years. Diagnoses included acute leukemia (n=18), non-Hodgkin's lymphoma (n=18), Hodgkin's Lymphoma (n=7), MDS (n= 6), multiple myeloma (n=3), myelofibrosis (n=2), CLL (n=2), severe aplastic anaemia (n=2), primary immunodeficiency (n=2), CML (n=1) and sickle cell disease (n=1). The original graft source was peripheral blood stem cells from a matched related donor (n=29), matched unrelated donor (n=18) and mismatched unrelated donor (n=15). Twenty-one (34%) patients had primary GF and 41 (66%) had secondary GF. Forty-three patients (69%) had GF in all 3 lineages and 19 patients (31%) had GF in 1 or 2 lineages. The median CD34+ cell dose/kg recipient weight was 3.2 x 106/kg (range, 0.47-14.2 x 106/kg) at a median of 181 days (range, 21-2718 days) following transplant. No response to CD34+ infusion was seen in 15 (24%) patients. Of the remaining 47 patien