Impact of conditioning regimen on peripheral blood hematopoietic cell transplant

Table 1 Conditioning regimen descriptions

Conditioning regimen	Number of patients	Protocol
Myeloablative without TBI (MA-noTBI)	38	Bu 12.8 mg/kg intravenous total dose and Cy 120 mg/kg total dose
Myeloablative with TBI (MA + TBI)	51	Cy 120 mg/kg total dose and TBI 1000-1350 cGy
Reduced intensity conditioning without TBI (RIC-noTBI)	118	Flu 125 mg/m2 total dose and Mel 140 mg/m2 total dose
Reduced intensity conditioning with TBI (RIC + TBI)	40	Flu 160 mg/m2 total dose, Mel 50-75 mg/m2 total dose, and TBI 400 cGy

Bu: Busulfan; Cy: Cyclophosphamide; Flu: Fludarabine; MA: Myeloablative; Mel: Melphalan; TBI: Total body irradiation.

Table 2 Patient characteristics for each of four conditioning regimen groups, n (%)

	MA-noTBI (n = 38)	MA+TBI (n = 51)	RIC-noTBI (n = 118)	RIC+TBI (n = 40)	P
Age at BMT					< 0.0001
Median-years (range)	47 (26-58)	36 (19-51)	54 (23-73)	61 (23-71)
< 40	6 (16)	29 (57)	22 (19)	3 (8)
≥ 40	32 (84)	22 (43)	96 (81)	37 (93)
Gender					NS
Female	21 (55)	19 (37)	45 (38)	22 (55)
Male	17 (45)	32 (63)	73 (62)	18 (45)
Diagnosis					< 0.0001
ALL	0	20 (39)	7 (6)	6 (15)
AML	11 (29)	28 (55)	58 (49)	14 (35)
CML	7 (18)	1 (2)	3 (3)	1 (3)
MDS/MPD	11 (29)	1 (2)	23 (19)	10 (25)
NHL/CLL/PLL	8 (21)	1 (2)	25 (21)	8 (20)
Other	1 (3)	0	2 (2)	1 (3)
Karnofsky Performance Status					0.03
≤ 70	8 (21)	8 (16)	35 (30)	13 (33)
80	13 (34)	15 (29)	51 (43)	14 (35)
≥ 90	17 (45)	28 (55)	32 (27)	13 (33)
BMT Regimen					< 0.0001
BuCy	36 (95)	0	0	0
CyTBI	0	47 (92)	0	0
FluCy	0	0	12 (10)	0
FluMel	0	0	102 (86)	0
FluMelTBI	0	0	0	40 (100)
Other	2 (5)	4 (8)	4 (3)	0
Sex Match					NS
Matched	24 (63)	30 (59)	70 (59)	27 (68)
Mismatched	14 (37)	21 (41)	48 (41)	13 (33)
Donor					< 0.0001
HLA Matched Related	33 (87)	31 (61)	54 (46)	17 (43)
HLA Matched Unrelated	5 (13)	20 (39)	64 (54)	23 (58)
GvHD Prophylaxis					< 0.0001
TacMtx	18 (47)	35 (69)	33 (28)	0
TacMMF	4 (11)	2 (4)	18 (15)	0
TacmMtxMMF	15 (39)	7 (14)	64 (54)	40 (100)
Single Agent	1 (3)	7 (14)	3 (3)	0
CMV Status					NS
R+D+	6 (16)	8 (16)	28 (24)	9 (23)
R+D-	14 (37)	12 (24)	35 (30)	12 (30)
R-D+	0	8 (16)	18 (15)	4 (10)
R-D-	18 (47)	23 (45)	37 (31)	15 (38)
BMI kg/m2					NS
Normal (< 30)	15 (39)	25 (49)	34 (29)	13 (33)
Overweight (25-< 30)	12 (32)	14 (27)	40 (34)	15 (38)
Obese (≥ 30-< 35)	7 (18)	7 (14)	28 (24)	7 (18)
Morbid (≥ 35)	4 (11)	5 (10)	16 (14)	5 (13)

MA: Myeloablative; TBI: Total body irradiation; RIC: Reduced intensity conditioning; ALL: Acute lymphoid leukemia; AML: Acute myeloid leukemia; CML: Chronic myeloid leukemia; MDS: Myelodysplastic syndrome; MPD: Myeloproliferative disorder; NHL: Non-Hodgkin lymphoma; CLL: Chronic lymphocytic leukemia; PLL: Prolymphocytic leukemia; Bu: Busulfan; Cy: Cyclophosphamide; Flu: Fludarabine; Mel: Melphalan; Tac: Tacrolimus; Mtx: Methotrexate; mMt: Micro dose methotrexate; MMF: Mycophenylate mofetil ; R: Recipient; D: Donor; BMI: Body mass index; NS: Not significant (P > 0.05).

Table 3 Time to neutrophil and platelet engraftment by CD34+ dose for each conditioning regimen group

	Conditioning group
	MA-noTBI (n = 38)	MA + TBI (n = 51)	RIC-noTBI (n = 118)	RIC + TBI (n = 40)
	Median days to engraftment (range)
Absolute neutrophil count > 500/mm3
CD34+ dose > 4 × 106/kg	14 (10-22)	14 (9-28)	14 (3-36)	15 (10-22)
CD34+ dose < 4 × 106/kg	14.5 (12-19)	19 (13-28)	15 (10-21)	18 (16-24)
P	NS	NS	NS	0.01
Platelet count > 20000/mm3
CD34+ dose > 4 × 106/kg	17 (3-171)	20 (13-81)	17 (3-1515)	17 (10-866)
CD34+ dose < 4 × 106/kg	19.5 (15-32)	34 (20-228)	22 (14-275)	18 (11-20)
P	NS	0.001	0.01	NS

MA: Myeloablative; TBI: Total body irradiation; RIC: Reduced intensity conditioning; NS: Not significant (P > 0.05).

Table 4 Multivariable analysis shows no association of cell doses with overall survival or progression free survival, except for total nucleated cell dose in the reduced intensity conditioning + total body irradiation group

Variable	Overall survival1					Progression free survival2
	All patients (n = 247)	MA-noTBI (n = 38)	MA + TBI (n = 51)	RIC-noTBI (n = 118)	RIC + TBI (n = 40)	All patients (n = 247)	MA-noTBI (n = 38)	MA + TBI (n = 51)	RIC-noTBI (n = 118)	RIC + TBI (n = 40)
CD3+ cell dose
< Median HR	1	1	1	1	1	1	1	1	1	1
> Median HR	1.1	1.0	0.5	1.3	0.8	1.0	1.1	0.4	1.4	0.6
95%CI	0.8-1.5	0.4-2.6	0.2-1.1	0.8-2.1	0.3-2.2	0.7-1.4	0.4-2.6	0.2-1.0	0.8-2.2	0.2-1.7
P	NS	NS	NS	NS	NS	NS	NS	0.05	NS	NS
CD4+ cell dose
< Median HR	1	1	1	1	1	1	1	1	1	1
> Median HR	1.2	1.1	0.6	1.2	2.0	1.1	1.1	0.5	0.3	1.5
95%CI	0.8-1.7	0.4-2.6	0.2-1.3	0.8-1.0	0.7-6.0	0.8-1.6	0.5-2.6	0.2-1.2	0.8-2.1	0.5-4.3
P	NS	NS	NS	NS	NS	NS	NS	NS	NS	NS
CD8+ cell dose
< Median HR	1	1	1	1	1	1	1	1	1	1
> Median HR	1.2	1.5	1.0	1.3	0.5	1.1	1.1	0.9	1.2	0.7
95%CI	0.8-1.6	0.5-4.2	0.4-2.3	0.8-2.1	0.2-1.8	0.8-1.5	0.5-2.8	0.4-2.0	0.8-2.0	0.2-2.0
P	NS	NS	NS	NS	NS	NS	NS	NS	NS	NS
TNC dose
< Median HR	1	1	1	1	1	1	1	1	1	1
> Median HR	0.8	1.0	0.7	0.9	0.2	0.8	1.1	0.7	1.1	0.2
95%CI	0.6-1.2	0.4-2.4	0.3-1.9	0.5-1.5	0.1-0.8	0.6-1.2	0.4-2.5	0.3-1.6	0.6-1.8	0.1-0.8
P	NS	NS	NS	NS	0.02	NS	NS	NS	NS	0.02
CD34+ cell dose
< 4 × 106/kg HR	1	1	1	1	1	1	1	1	1	1
4-8 × 106/kg HR	1.0	0.5	1.3	1.1	0.6	0.8	0.7	1.2	1.0	0.6
95%CI	0.6-1.5	0.2-1.4	0.4-4.4	0.6-1.9	0.1-2.3	0.6-1.4	0.2-2.1	0.4-4.0	0.6-1.8	0.2-2.6
P	NS	NS	NS	NS	NS	NS	NS	NS	NS	NS
> 8 × 106/kg HR	1.0	1.3	0.7	1.1	0.5	0.9	1.5	0.6	1.1	0.5
95%CI	0.6-1.5	0.4-4.0	0.2-2.3	0.5-2.0	0.1-2.4	0.6-1.4	0.5-4.6	0.2-2.0	0.6-2.0	0.1-2.6
P	NS	NS	NS	NS	NS	NS	NS	NS	NS	NS

¹Adjusted for age, KPS and BMI;

²Adjusted for KPS and BMI. KPS: Karnofsky performance score; BMI: Body mass index; HR: Hazard ratio; 95%CI: 95% confidence interval; MA: Myeloablative; TBI: Total body irradiation; RIC: Reduced intensity conditioning; NS: Not significant (P > 0.05).

Table 5 Summary of correlations between cell doses demonstrating low correlation between total nucleated cell dose and CD8+ and CD34+ cell doses and moderate correlation with CD3+ and CD4+ cell doses

	CD3+ dose	CD4+ dose	CD8+ dose	CD34+ dose
CD4+ dose
R	0.91
R2	0.83
P	< 0.0001
CD8+ dose
R	0.81	0.55
R2	0.66	0.30
P	< 0.0001	< 0.0001
CD34+ dose
R	0.20	0.21	0.11
R2	0.04	0.04	0.01
P	0.0012	0.0009	NS
Total nucleated cell dose
R	0.71	0.64	0.56	0.38
R2	0.50	0.41	0.31	0.14
P	< 0.0001	< 0.0001	< 0.0001	< 0.0001

R: Pearson product moment correlation coefficient, R > 0.8 indicates highly correlated cell doses, R < 0.4 indicates low correlation between cell doses, R²: The square of the Pearson correlation, R²: 0.83 indicates 83% of the variance in one cell dose (e.g., CD3+) is determined by the other (e.g., CD4+); NS: Not significant (P > 0.05).