Tempo of neutrophil recovery and the definition of myeloid engraftment after allogeneic hematopoietic stem cell transplantation (HSCT) in patients not receiving growth factors post-transplant

Abstract

Time to myeloid recovery after HSCT is usually defined as the first of 3 consecutive days with an absolute neutrophil count (ANC) of 0.5 × 109/L. HSCT registries and FACT require ANC ≥0.5 for 3 days as adequate evidence of engraftment. The first day with ANC ≥0.5 can be considered the day of engraftment in autograft recipients (Bone Marrow Transplant 2002;30:749–752). We have shown this in 78 allograft recipients too (Rihn et al. ASH 2002). However, the allograft study was limited by the fact that most patients had received G-CSF post-transplant, and the stem cell source was not uniform. We have now studied 49 patients allografted using blood stem cells who did not receive post-transplant G-CSF to see if the tempo of myeloid recovery was sustained. The conditioning regimen, 100 mg/m2 melphalan (+ 50 mg/kg cyclophosphamide if no prior autograft), induced severe neutropenia (ANC <0.1) in all patients. The CD34+ cell dose was 1.4–11.8 × 106/kg (median 5.0). The time to ANC ≥0.5 was 10–23 days (median 13). Potentially acceptable evidence of engraftment, ANC on the 2 days following an initial value of ≥0.5, was available in 46 (94%). The remaining 3 patients had ANC ≥0.5 for the first and second days but died after that (n = 2) or did not have a differential count available (n = 1). ANC increased from day 1 to 2 in 41 of 46 patients, and declined in 5 (≥0.5 in 2, <0.5 in 3. 2 of the latter had ANC ≥0.5 the next day). ANC increased from day 2 to 3 in 44 of 46 patients, and declined in 2 (≥0.5 in both). ANC increased from day 1 to 3 in 45 of 46 patients; declining below 0.5 in 1 patient. Thus, in 43 of 46 patients, the first day with ANC 0.5 was also the first of 3 consecutive days with ANC 0.5. These data support our previous observations that in the majority of allografted patients, ANC does not decline significantly immediately after recovering to ≥0.5 whether or not myeloid growth factors are administered post-transplant. Therefore, it is not essential to obtain WBC counts on 3 consecutive days to define myeloid engraftment. The first day with ANC ≥0.5 should be considered the day of myeloid engraftment in allograft as well as autograft recipients. This simple change in definition and practice has significant potential impact on convenience (unnecessary clinic visits for patients; particularly out-patient mini-allografts), cost (blood counts, home health visits, ancillary charges), and compliance (acceptable definition of engraftment by HSCT registries and FACT). TableDay 1Day 2Day 3ANC (109/L)0.74 (0.53–2.10)1.43 (0.36–10.94)2.46 (0.44–30.74)Change from Day 1 (%)+67 (−36 to +574)+176 (−21 to +1793)Change from Day 2 (%)+50 (−17 to +1925)ANC <0.5 (n)03 (7%)1 (2%)