Table 1 -.
Studies published to date assessing the association of post-transplantation absolute lymphocyte counts (ALC) with clinical outcomes
| Study (year) | Patient characteristics | ALC timepoint and cutoffs assessed and rationale for their selection | OS | RFS | NRM | RI | aGVHD | cGVHD |
|---|---|---|---|---|---|---|---|---|
| Rigoni L, 201515 | 100 chemo-responsive AML/ALL/MDS pts. All sources and donors. 78% MA, 22% RIC | Timepoints and cutoff arbitrarily chosen | OS longer in high ALC group. HR: | HR: | ||||
| 300@d21 (30%) | 1.3 (0.7–2.6) | 1.2(0.6–2.6) | 25% vs. 26% (NS) | 76% vs. 52% (NS) | 33% vs. 36% (NS) | |||
| 300@d30 (18%) | 2.2 (1.0–4.7) | 2.0 (0.9–4.4) | 12% vs. 29% (NS) | 94% vs. 50% (0.003) | 46% vs. 34% (NS) | |||
| Kim HT, 201513 | 1109 pts. All diseases. UCB and haplo excluded. 48% MA, 52% RIC | Timepoints arbitrarily, cutoff b/o RFS curves | At 5 yr: | At 5 yr: | At 5 yr: | pts with <200 at any time point (14% of all pts) vs. >200 at m1, m2 and m3: 40% vs. 43% (NS) | ||
| 200@m1 (8%) | 30% vs. 45% (<0.001) | 19% vs. 38% (<0.001) | 33% vs. 20% (0.002) | |||||
| 200@m2 (6%) | 28% vs. 49% (<0.001) | 25% vs. 41% (<0.001) | 44% vs. 19% (<0.001) | |||||
| 200@m3 (6%) | 27% vs. 53% (<0.001) | 22% vs. 45% (<0.001) | 41% vs. 18% (<0.001) | |||||
| Yamamo to, 201416 | 206 AML/ALL/MDS pts. MA and RIC. All sources and donors | Timepoint d100 selected to exclude aGVHD effect. Cutoff b/o OS curves | OS longer in high ALC group. HR: | NRM lower in high ALC group. HR: | ||||
| 500@d100 (18%) | 2.4 (1.3–4.5) | 2.8 (1.1–6.8) | 1.4 (0.7–3.0) | |||||
| Michelis FV, 201417 | 191 AML pts in CR. MRD or MUD. PB only. MA and RIC | Cutoff arbitrarily chosen. Timepoint b/o the median # of days to achieve ALC500 | RI lower in high ALC group | |||||
| 500@d28 (42%) | NS in MVA | NS in MVA | 0.49 (0.26–0.92) | |||||
| Han DK, 201318 | 69 children with heme malignancies. 64 MA, 5 RIC. All sources and donors | Cutoff b/o prelim analyses between ALC200, 300, 400, 500 | At 5 yr: | At 5 yr | At 5 yr: | GII-IV incidence: | Extensive | |
| 500@d21 (41%) | 62% vs. 67% (NS) | 19% vs. 16% (NS) | 20% vs. 22% (NS) | 14% vs. 15% (NS) | ||||
| 500@d30 (28%) | 53% vs. 71% (0.043) (NS on MVA) | 34% vs. 11% (0.019 | 20% vs. 22% (NS) | 29% vs. 17% (NS) | 11% vs. 16% (NS) | |||
| DeCook LJ, 201219 | 118 pts with heme malignancies. RIC with Flu/Mel. PB and BM. All donors | Rationale not provided | UVar OS analyses: On MVar only d100 was sig (0.049) | |||||
| 300@d15 (57%) | 0.25 | |||||||
| 300@d30 (6%) | <0.001 | |||||||
| 300@d60 (11%) | <0.001 | |||||||
| 300@d100 (18%) | <0.001 | |||||||
| Le Blanc K, 200920 | 102 pts AML-CML-MDS only, MA only, MUD only, PB and BM | MVarA performed with ALC on day 30 as a continuous variable. d30 chosen b/o previous studies | NS on MVarA | sig increases with ALC (0.04) | sig decreases with ALC (<0.05) | |||
| Afzal S, 200921 | 71 children with AML in CR. All sources. | Rationale not provided | At 3 yr: | At 3 yr: | G III-IV: | Extensive: | ||
| 300@d21 | 14% vs. 27% (NS) | 25% vs. 20% (NS) | 16% vs. 12% (NS) | 18% vs. 13% (NS) | ||||
| 300@d30 | 21% vs. 13% (NS) | 21% vs. 26% (NS) | 18% vs. 16% (NS) | 21% vs. 11% (NS) | ||||
| Ishaqi MK, 200822 | 132 children with ALL in CR. All sources. MA only | Rationale not provided | At 3 yr: | At 3 yr: | At 3 yr: | G III-IV: | Extensive: | |
| 300@d21 | 42% vs. 66% (0.02) | 17% vs. 19% (NS) | 40% vs. 10% (0.002) | 32%−24% (NS) | 13% vs. 12% (NS) | |||
| 300@d30 | 30% vs. 57% (<0.001) | 25% vs. 14% (NS) | 46% vs. 26% (0.01) | 31% vs. 29% | 19% vs. 9% (NS) | |||
| Savani BN, 200723 | 160 pts with leukemia after TCD from MRD with MA. BM and PB grafts | d30 chosen as a marker for NK cells.Cutoff b/o median ALC on d30 | OS longer in high ALC group | NRM lower in high ALC group | Worsening effect of low ALC seen only in AML/MDS but not in ALL pts | Low ALC a/w more aGVHD.G II-IV: | High ALC a/w more cGVHD | |
| 450@d30 | 2.7 (1.03–5.1) | 3.6 (1.2–10.6) | 3(1.5–6) | 1.8 (1.1–2.9) | 0.55 (0.34–0.87) | |||
| Kim DH, 200414 | 82 pts with heme malignancies. MA and RIC. BM and PB grafts. All donors | d21 chosen because it was an early timemark. Rationale for ALC cutoff not provided | OS longer in high ALC group | RFS longer in high ALC group | At 1 yr: | RI lower in high ALC group | ||
| 350@d21 | 2.7 (1.2–6.0) | 2.8 (1.4–5.8) | 52% vs. 31% (NS) | 2.5 (1.1–6.2) | ||||
| Kumar S, 200324 | 43 pts with ALL; MA only; BM only | Assessed measures: ALC@d21 => 150, 175, 200, 225 ALC@d30 => 150, 175, 200, 225 |
RFS longer in high ALC group | RI lower in high ALC group | ||||
| 175@d21 | p = 0.0028 | 4.5 (1.2–16.6) | NS | NS | ||||
| Chakrabarti S, 200325 | 29 pts with heme malignancies. TCD BM or PB followed by TCAB. UCB and haplo excluded | Timepoint chosen arbitrarily. Cutoff b/o median ALC on d30 | OS longer in high ALC group | |||||
| 350@d30 | 18.5 (1.3–256) | NS | ||||||
| Kumar S, 200126 | 87 AML pts. BM only. Syngeneics and haplos excluded | Assessed measures: ALC@d21: 100, 150, 200 ALC@d30: 125, 150, 175, 200, 225 | OS longer in high ALC group | RFS longer in high ALC group | RI lower in high ALC group | |||
| 150@d30 with highest sig in RI | 0.0047 UVar | 0.0079 UVar | 8.2 (2.2–30.1) | |||||
| Powles R, 199827 | 201 AML pts. BM only. MA only. MRD only | d27,28,29,30 timepoints and ALC 100, 200, 300 cutoffs assessed | At 1 yr: | |||||
| 200@d29 | 25% vs. 65% (0.003) | 2.9 (0.9–9.1) |
*:
Where percentages are given for OS, RFS, NRM, RI, and GVHD incidences, the first and second percentages indicate the survival/incidence in low and high absolute lymphocyte count groups, respectively
aGVHD: acute graft-versus-host disease, ALC: Absolute lymphocyte count, ALL: Acute lymphoid leukemia, AML: Acute myeloid leukemia, ATG: Anti-thymocyte globulin, BM: Bone marrow, b/o: based on, cGVHD: chronic graft-versus-host disease, CR: Complete remission, d: day, haplo: Haploidentical donor, HR: Hazard ratio, m: month, MA: Myeloablative, MDS: Myelodysplastic syndrome, MRD: Matched-related donor, MUD: Matched unrelated donor, NRM: Non-relapse mortality, NS: Not significant, OS: Overall survival PB: Peripheral blood, pts: patients, RFS: Relapse-free survival, RI: Relapse incidence, RIC: Reduced intensity conditioning, sig: significant, TBI: Total body irradiation, TCAB: T cell add-back, TCD: T cell depleted, UCB: Umbilical cord blood, UV: Univariate, yr: year