Impact of conditioning regimen on peripheral blood hematopoietic cell transplant

doi:10.5306/wjco.v10.i2.86

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Feb 24, 2019 (publication date) through May 14, 2024

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World Journal of Clinical Oncology

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Baishideng Publishing Group Inc, 7041 Koll Center Parkway, Suite 160, Pleasanton, CA 94566, USA

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World J Clin Oncol. Feb 24, 2019; 10(2): 86-97
Published online Feb 24, 2019. doi: 10.5306/wjco.v10.i2.86

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
Variable	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).

Citation: Burns M, Singh AK, Hoefer CC, Zhang Y, Wallace PK, Chen GL, Platek A, Winslow TB, Iovoli AJ, Choi C, Ross M, McCarthy PL, Hahn T. Impact of conditioning regimen on peripheral blood hematopoietic cell transplant. World J Clin Oncol 2019; 10(2): 86-97
URL: https://www.wjgnet.com/2218-4333/full/v10/i2/86.htm
DOI: https://dx.doi.org/10.5306/wjco.v10.i2.86