J Hematol

Journal of Hematology, ISSN 1927-1212 print, 1927-1220 online, Open Access

Article copyright, the authors; Journal compilation copyright, J Hematol and Elmer Press Inc

Journal website https://www.thejh.org

Original Article

Volume 12, Number 1, February 2023, pages 16-26

Clofarabine in Pediatric Acute Relapsed or Refractory Leukemia: Where Do We Stand on the Bridge to Hematopoietic Stem Cell Transplantation?

Figure 1. OS by leukemia subtypes. ALL: acute lymphoblastic leukemia; AML: acute myeloid leukemia; OS: overall survival.

Figure 2. OS by HSCT and non-HSCT groups. OS: overall survival; HSCT: hematopoietic stem cell transplantation.

Figure 3. OS by HSCT and non-HSCT groups in ALL patients. OS: overall survival; HSCT: hematopoietic stem cell transplantation; ALL: acute lymphoblastic leukemia.

Figure 4. OS by HSCT and non-HSCT groups in AML patients. OS: overall survival; HSCT: hematopoietic stem cell transplantation; AML: acute myeloid leukemia.

**Table 1.** Patient and Underlying Disease Characteristics (N = 43)
	ALL (30, 69.8%)	AML (13, 30.2%)	Total	P value
Values are presented as median (range) for continuous and numbers (percentage) for discrete data. ALL: acute lymphoblastic leukemia; AML: acute myeloid leukemia; BM: bone marrow; WBC: white blood cell; Hb: hemoglobin.
Median age at diagnosis, years, (range)	5.1 (0.4 - 13.0)	6.0 (1.1 - 11.7)	5.4 (0.4 - 13.0)	0.979
Gender n (%)				0.460
Female	7 (23.3%)	5 (38.5%)	12 (27.9%)
Male	23 (76.7%)	8 (61.5%)	31 (72.1%)
Leukemia subtypes, n (%)
B-cell	25 (83.3%)	-
T-cell	4 (13.3%)	-
Biphenotypic	1 (3.3%)	-
M0	-	None
M1	-	None
M2	-	None
M3	-	None
M4	-	None
M5	-	1 (7.7%)
M6	-	None
M7	-	2 (15.4%)
Unknown	-	10 (76.9%)
Cytogenetics
Favorable	14 (46.7%)	-
Unfavorable	13 (43.3%)	-
Unknown	3 (10.0%)	-
Low risk	-	1 (7.7%)
Intermediate risk	-	2 (15.4%)
High risk	-	10 (76.9%)
Risk group				< 0.001
Low	None	1 (7.7%)	1 (2.3%)
Intermediate	None	2 (15.4%)	2 (4.7%)
Standard	15 (50.0%)	None	15 (34.9%)
High	15 (50.0%)	9 (69.2%)	24 (55.8%)
Very high	None	1 (7.7%)	1 (2.3%)
CNS disease				0.841
CNS-1	22 (73.3%)	11 (84.6%)	33 (76.7%)
CNS-2	6 (20.0%)	1 (7.7%)	7 (16.3%)
CNS-3	2 (6.7%)	1 (7.7%)	3 (7.0%)
Hematological profile, median (range)
Pre-treatment WBC	32.6 (1.5 - 440.0)	11.6 (0.9 - 226.0)	-
Post-treatment WBC	2.6 (0.1 - 20.8)	4.9 (0.1 - 6.6)	-
Pre-treatment platelets	44.0 (0.6 - 279.0)	66.0 (0.7 - 252.0)	-
Post-treatment platelets	38.5 (6.0 - 482.0)	27.0 (6.0 - 220.0)	-
Pre-treatment Hb	86.5 (49.0 - 123.0)	93.0 (70.0 - 120.0)	-
Post-treatment Hb	87.0 (69.0 - 124.0)	85.0 (74.0 - 109.0)	-
Clofarabine indications				0.503
Refractory disease	14 (46.7%)	4 (30.8%)	18 (41.9%)
Relapse	16 (53.3%)	9 (69.2%)	25 (58.1%)
BM	8 (50.0%)	8 (88.9%)
CNS	1 (6.2%)	1 (11.1%)
Extramedullary	1 (6.2%)	None
BM + CNS	5 (31.2%)	None
BM + testicular	1 (6.2%)	None
Relapse I	5 (31.2%)	3 (33.3%)	8 (32.0%)
Relapse II	11 (68.8%)	6 (66.7%)	17 (68.0%)
Median time to cycle 1 of clofarabine months, (range)	15.8 (1.1 - 77.8)	11.2 (1.1 - 36.0)	13.4 (1.1 - 77.8)	0.428
Minimum residual disease (+)
Day 14	10 of 25 (40.0%)	-
Day 28	15 of 30 (50.0%)	-
Post-consolidation	5 of 11 (45.5%)	-
Post-induction I	-	11 of 12 (91.7%)
Post-induction II	-	5 of 10 (50.0%)
Post-intensification I	-	3 of 7 (42.9%)
Number of clofarabine cycles (per case)				1.000
One cycle	19 (63.3%)	8 (61.5%)	27 (62.8%)
Two cycles	11 (36.7%)	5 (38.5%)	16 (37.2%)

Table 1. Patient and Underlying Disease Characteristics (N = 43)

ALL (30, 69.8%)

AML (13, 30.2%)

Total

P value

Values are presented as median (range) for continuous and numbers (percentage) for discrete data. ALL: acute lymphoblastic leukemia; AML: acute myeloid leukemia; BM: bone marrow; WBC: white blood cell; Hb: hemoglobin.

Median age at diagnosis, years, (range)

5.1 (0.4 - 13.0)

6.0 (1.1 - 11.7)

5.4 (0.4 - 13.0)

0.979

Gender n (%)

0.460

Female

7 (23.3%)

5 (38.5%)

12 (27.9%)

Male

23 (76.7%)

8 (61.5%)

31 (72.1%)

Leukemia subtypes, n (%)

B-cell

25 (83.3%)

T-cell

4 (13.3%)

Biphenotypic

1 (3.3%)

None

1 (7.7%)

None

2 (15.4%)

Unknown

10 (76.9%)

Cytogenetics

Favorable

14 (46.7%)

Unfavorable

13 (43.3%)

Unknown

3 (10.0%)

Low risk

1 (7.7%)

Intermediate risk

2 (15.4%)

High risk

10 (76.9%)

Risk group

< 0.001

Low

None

1 (7.7%)

1 (2.3%)

Intermediate

None

2 (15.4%)

2 (4.7%)

Standard

15 (50.0%)

None

15 (34.9%)

High

15 (50.0%)

9 (69.2%)

24 (55.8%)

Very high

None

1 (7.7%)

1 (2.3%)

CNS disease

0.841

CNS-1

22 (73.3%)

11 (84.6%)

33 (76.7%)

CNS-2

6 (20.0%)

1 (7.7%)

7 (16.3%)

CNS-3

2 (6.7%)

1 (7.7%)

3 (7.0%)

Hematological profile, median (range)

Pre-treatment WBC

32.6 (1.5 - 440.0)

11.6 (0.9 - 226.0)

Post-treatment WBC

2.6 (0.1 - 20.8)

4.9 (0.1 - 6.6)

Pre-treatment platelets

44.0 (0.6 - 279.0)

66.0 (0.7 - 252.0)

Post-treatment platelets

38.5 (6.0 - 482.0)

27.0 (6.0 - 220.0)

Pre-treatment Hb

86.5 (49.0 - 123.0)

93.0 (70.0 - 120.0)

Post-treatment Hb

87.0 (69.0 - 124.0)

85.0 (74.0 - 109.0)

Clofarabine indications

0.503

Refractory disease

14 (46.7%)

4 (30.8%)

18 (41.9%)

Relapse

16 (53.3%)

9 (69.2%)

25 (58.1%)

8 (50.0%)

8 (88.9%)

CNS

1 (6.2%)

1 (11.1%)

Extramedullary

1 (6.2%)

None

BM + CNS

5 (31.2%)

None

BM + testicular

1 (6.2%)

None

Relapse I

5 (31.2%)

3 (33.3%)

8 (32.0%)

Relapse II

11 (68.8%)

6 (66.7%)

17 (68.0%)

Median time to cycle 1 of clofarabine months, (range)

15.8 (1.1 - 77.8)

11.2 (1.1 - 36.0)

13.4 (1.1 - 77.8)

0.428

Minimum residual disease (+)

Day 14

10 of 25 (40.0%)

Day 28

15 of 30 (50.0%)

Post-consolidation

5 of 11 (45.5%)

Post-induction I

11 of 12 (91.7%)

Post-induction II

5 of 10 (50.0%)

Post-intensification I

3 of 7 (42.9%)

Number of clofarabine cycles (per case)

1.000

One cycle

19 (63.3%)

8 (61.5%)

27 (62.8%)

Two cycles

11 (36.7%)

5 (38.5%)

16 (37.2%)

**Table 2.** Treatment Response, Outcome and Clofarabine Regimen Related Toxicity
	ALL (30, 69.8%)	AML (13, 30.2%)	Total	P value
Values are presented as median (range) for continuous and numbers (percentage) for discrete data. ^aBone marrow was not done for three cases post cycle 1. ^bMantel-Haenszel. ALL: acute lymphoblastic leukemia; AML: acute myeloid leukemia; HSCT: hematopoietic stem cell transplantation; BM: bone marrow; WBC: white blood cell; CR: complete response; HCT: hematopoietic cell transplantation.
Post-clofarabine bone marrow response^a				0.498
Positive	17 (58.6%)	5 (45.5%)	22 (55.0%)
Negative	12 (41.4%)	6 (54.5%)
After cycle 1 (negative BM)	13 of 29 (44.8%)	6 of 11 (54.5%)	19 of 40 (47.5%)
After cycle 2 (negative BM)	5 of 11 (45.4%)	4 of 5 (80.0%)	9 of 16 (56.3%)
Overall response to clofarabine treatment				0.747
Failure	18 (60.0%)	7 (53.8%)	25 (58.1%)
CR	12 (40.0%)	6 (46.2%)	18 (41.9%)
Hematopoietic recovery	13 (68.4%)	6 (31.6%)	19 (44.2%)	1.000
Incomplete	7 (53.8%)	3 (50.0%)	10 (52.6%)
Complete	6 (46.2%)	3 (50.0%)	9 (47.4%)
Treatment (clofarabine) failure by
Treatment cycles				0.262^b
One cycle only	12 (63.2%)	6 (75.0%)	18 (66.7%)
Two cycles	6 (54.5%)	1 (20.0%)	7 (43.8%)
Pre-treatment disease status				0.557^b
Relapse	10 (62.5%)	3 (33.3%)	13 (52.0%)
Refractory disease	8 (57.1%)	4 (100.0%)	12 (66.7%)
Initial risk assignment				0.060/1.000
Low	-	1 (100.0%)	1 (100.0%)
Intermediate	-	1 (50.0%)	1 (50.0%)
Standard	6 (40.0%)	-	6 (40.0%)
High	12 (80.0%)	4 (44.4%)	16 (66.7%)
Very high	-	1 (100.0%)	1 (100.0%)
Cytology (n = 23)				0.440/1.000
Favorable	7 (50.0%)		7 (50.0%)
Unfavorable	9 (69.2%)		9 (69.2%)
Low risk	-	1 (100.0%)	1 (100.0%)
Intermediate risk	-	1 (50.0%)	1 (50.0%)
High risk	-	5 (50.0%)	5 (50.0%)
CNS disease				0.565/0.192
CNS-1	12 (54.5%)	7 (63.6%)	19 (57.6%)
CNS-2	4 (66.7%)	None	4 (57.1%)
CNS-3	2 (100.0%)	None	2 (66.7%)
Site of relapse prior to clofarabine				0.502/0.333
BM	6 (75.0%)	2 (25.0%)	8 (50.0%)
CNS	None	1 (100.0%)	1 (50.0%)
Extramedullary	1 (100.0%)	None	1 (100.0%)
BM + CNS	2 (40.0%)	None	2 (40.0%)
BM + testicular	1 (100.0%)	None	1 (100.0%)
Risk assignment before relapse				0.500/NA
High	8 (57.1%)	3 (33.3%)	11 (47.8%)
Very high	2 (100.0%)	None	2 (100.0%)
Number of relapses				1.000/1.000
Relapse I	3 (60.0%)	1 (33.3%)	4 (50.0%)
Relapse II	7 (63.6%)	2 (33.3%)	9 (52.9%)
Stem cell transplantation				0.332
Negative	19 (63.3%)	6 (46.2%)	25 (58.1%)
Positive	11 (36.7%)	7 (53.8%)	18 (41.9%)
Post-clofarabine CR				1.000
HSCT (-)	2 (16.7%)	None	2 (11.1%)
HSCT (+)	10 (83.3%)	6 (100.0%)	16 (88.9%)
Post-clofarabine treatment failure				0.529
HSCT (-)	17 (73.9%)	6 (85.7%)	23 (92.0%)
HSCT (+)	1 (5.6%)	1 (14.3%)	2 (8.0%)
Median time to HCT from cycle 1, months, (range)	2.7 (1.2 - 6.4)	2.6 (1.4 - 5.3)	2.7 (1.2 - 6.4)	0.930
Survival status				1.000
Alive	6 (20.0%)	2 (15.4%)	8 (18.6%)
Expired	24 (80.0%)	11 (84.6%)	35 (81.4%)
Post-clofarabine CR				0.363
Alive	5 (41.7%)	1 (16.7%)	6 (33.3%)
Expired	7 (58.3%)	5 (83.3%)	12 (66.7%)
Post-clofarabine treatment failure				0.490
Alive	1 (5.6%)	1 (14.3%)	2 (8.0%)
Expired	17 (94.4%)	6 (85.7%)	23 (92.0%)
Overall survival (5 year)	40.9±9.3%	15.4±10.0%	32.7±7.3%	0.492
HSCT (-), n = 25, events = 23	28.7±10.7%	0.0±0.0%	21.4±8.4%
HSCT (+), n = 18, events = 12	62.3±15.0%	28.6±17.1%	48.1±12.1%
	(P = 0.140)	(P = 0.009)	(P = 0.024)

Table 2. Treatment Response, Outcome and Clofarabine Regimen Related Toxicity

ALL (30, 69.8%)

AML (13, 30.2%)

Total

P value

Values are presented as median (range) for continuous and numbers (percentage) for discrete data. ^aBone marrow was not done for three cases post cycle 1. ^bMantel-Haenszel. ALL: acute lymphoblastic leukemia; AML: acute myeloid leukemia; HSCT: hematopoietic stem cell transplantation; BM: bone marrow; WBC: white blood cell; CR: complete response; HCT: hematopoietic cell transplantation.

Post-clofarabine bone marrow response^a

0.498

Positive

17 (58.6%)

5 (45.5%)

22 (55.0%)

Negative

12 (41.4%)

6 (54.5%)

After cycle 1 (negative BM)

13 of 29 (44.8%)

6 of 11 (54.5%)

19 of 40 (47.5%)

After cycle 2 (negative BM)

5 of 11 (45.4%)

4 of 5 (80.0%)

9 of 16 (56.3%)

Overall response to clofarabine treatment

0.747

Failure

18 (60.0%)

7 (53.8%)

25 (58.1%)

12 (40.0%)

6 (46.2%)

18 (41.9%)

Hematopoietic recovery

13 (68.4%)

6 (31.6%)

19 (44.2%)

1.000

Incomplete

7 (53.8%)

3 (50.0%)

10 (52.6%)

Complete

6 (46.2%)

3 (50.0%)

9 (47.4%)

Treatment (clofarabine) failure by

Treatment cycles

0.262^b

One cycle only

12 (63.2%)

6 (75.0%)

18 (66.7%)

Two cycles

6 (54.5%)

1 (20.0%)

7 (43.8%)

Pre-treatment disease status

0.557^b

Relapse

10 (62.5%)

3 (33.3%)

13 (52.0%)

Refractory disease

8 (57.1%)

4 (100.0%)

12 (66.7%)

Initial risk assignment

0.060/1.000

Low

1 (100.0%)

Intermediate

1 (50.0%)

Standard

6 (40.0%)

High

12 (80.0%)

4 (44.4%)

16 (66.7%)

Very high

1 (100.0%)

Cytology (n = 23)

0.440/1.000

Favorable

7 (50.0%)

Unfavorable

9 (69.2%)

Low risk

1 (100.0%)

Intermediate risk

1 (50.0%)

High risk

5 (50.0%)

CNS disease

0.565/0.192

CNS-1

12 (54.5%)

7 (63.6%)

19 (57.6%)

CNS-2

4 (66.7%)

None

4 (57.1%)

CNS-3

2 (100.0%)

None

2 (66.7%)

Site of relapse prior to clofarabine

0.502/0.333

6 (75.0%)

2 (25.0%)

8 (50.0%)

CNS

None

1 (100.0%)

1 (50.0%)

Extramedullary

1 (100.0%)

None

1 (100.0%)

BM + CNS

2 (40.0%)

None

2 (40.0%)

BM + testicular

1 (100.0%)

None

1 (100.0%)

Risk assignment before relapse

0.500/NA

High

8 (57.1%)

3 (33.3%)

11 (47.8%)

Very high

2 (100.0%)

None

2 (100.0%)

Number of relapses

1.000/1.000

Relapse I

3 (60.0%)

1 (33.3%)

4 (50.0%)

Relapse II

7 (63.6%)

2 (33.3%)

9 (52.9%)

Stem cell transplantation

0.332

Negative

19 (63.3%)

6 (46.2%)

25 (58.1%)

Positive

11 (36.7%)

7 (53.8%)

18 (41.9%)

Post-clofarabine CR

1.000

HSCT (-)

2 (16.7%)

None

2 (11.1%)

HSCT (+)

10 (83.3%)

6 (100.0%)

16 (88.9%)

Post-clofarabine treatment failure

0.529

HSCT (-)

17 (73.9%)

6 (85.7%)

23 (92.0%)

HSCT (+)

1 (5.6%)

1 (14.3%)

2 (8.0%)

Median time to HCT from cycle 1, months, (range)

2.7 (1.2 - 6.4)

2.6 (1.4 - 5.3)

2.7 (1.2 - 6.4)

0.930

Survival status

1.000

Alive

6 (20.0%)

2 (15.4%)

8 (18.6%)

Expired

24 (80.0%)

11 (84.6%)

35 (81.4%)

Post-clofarabine CR

0.363

Alive

5 (41.7%)

1 (16.7%)

6 (33.3%)

Expired

7 (58.3%)

5 (83.3%)

12 (66.7%)

Post-clofarabine treatment failure

0.490

Alive

1 (5.6%)

1 (14.3%)

2 (8.0%)

Expired

17 (94.4%)

6 (85.7%)

23 (92.0%)

Overall survival (5 year)

40.9±9.3%

15.4±10.0%

32.7±7.3%

0.492

HSCT (-), n = 25, events = 23

28.7±10.7%

0.0±0.0%

21.4±8.4%

HSCT (+), n = 18, events = 12

62.3±15.0%

28.6±17.1%

48.1±12.1%

(P = 0.140)

(P = 0.009)

(P = 0.024)

**Table 3.** Clofarabine Regimen-Related Toxicity
	ALL (30, 69.8%)	AML (13, 30.2%)	Total (43, 100%)
Values are presented as numbers (percentage). Grading is as per CTCAE 5.0. Resolution of hepatic toxicity was seen in 20 cases while three patients succumbed to their disease. ALL: acute lymphoblastic leukemia; AML: acute myeloid leukemia; CTCAE: Common Terminology Criteria for Adverse Events; ICU: intensive care unit; NOS: not otherwise specified.
Observed toxicity	26 (86.7%)	13 (100.0%)	39 (90.7%)
Mucosal infection	7 (23.3%)	5 (38.5%)	12 (27.9%)
Grade 1	-	-	-
Grade 2	-	1 (7.7%)	1 (2.3%)
Grade 3	5 (16.7%)	-	5 (11.6%)
Grade 4	2 (6.7%)	4 (30.8%)	6 (14.0%)
Hepatobiliary disorders	16 (53.3%)	7 (53.8%)	23 (53.5%)
Hepatic failure	3 (10.0%)	-	3 (7.0%)
Sinusoidal obstruction syndrome (grade 2)	1 (3.3%)	-	1 (2.3%)
Hyperbilirubinemia	5 (16.7%)	2 (15.4%)	7 (16.3%)
Grade 1	1 (3.3%)	1 (7.7%)	2 (4.7%)
Grade 2	-	1 (7.7%)	1 (2.3%)
Grade 3	4 (13.3%)	-	4 (9.3%)
Grade 4	-	-	-
Transaminitis	16 (53.3%)	7 (53.8%)	23 (53.5%)
Grade 1	2 (6.7%)	1 (7.7%)	3 (7.0%)
Grade 2	4 (13.3%)	-	4 (9.3%)
Grade 3	6 (20.0%)	6 (46.2%)	12 (27.9%)
Grade 4	4 (13.3%)	-	4 (9.3%)
Febrile neutropenia	24 (80.0%)	12 (92.3%)	36 (83.7%)
Encephalopathy (grade 2)	-	1 (100%)	1 (2.3%)
Renal and urinary disorders
Acute kidney injury (grade 2)	-	2 (15.4%)	2 (4.7%)
Infections and infestations
Bacterial infections	17 (56.7%)	8 (61.5%)	25 (58.1%)
Viral infections	5 (16.7%)	1 (7.7%)	6 (14.0%)
Fungal infections	8 (26.7%)	4 (30.8%)	12 (27.9%)
Sepsis (NOS)	9 (30.0%)	4 (30.8%)	13 (30.2%)
ICU admissions	13 (43.3%)	6 (46.2%)	19 (44.2%)

Table 3. Clofarabine Regimen-Related Toxicity

ALL (30, 69.8%)

AML (13, 30.2%)

Total (43, 100%)

Values are presented as numbers (percentage). Grading is as per CTCAE 5.0. Resolution of hepatic toxicity was seen in 20 cases while three patients succumbed to their disease. ALL: acute lymphoblastic leukemia; AML: acute myeloid leukemia; CTCAE: Common Terminology Criteria for Adverse Events; ICU: intensive care unit; NOS: not otherwise specified.

Observed toxicity

26 (86.7%)

13 (100.0%)

39 (90.7%)

Mucosal infection

7 (23.3%)

5 (38.5%)

12 (27.9%)

Grade 1

Grade 2

1 (7.7%)

1 (2.3%)

Grade 3

5 (16.7%)

5 (11.6%)

Grade 4

2 (6.7%)

4 (30.8%)

6 (14.0%)

Hepatobiliary disorders

16 (53.3%)

7 (53.8%)

23 (53.5%)

Hepatic failure

3 (10.0%)

3 (7.0%)

Sinusoidal obstruction syndrome (grade 2)

1 (3.3%)

1 (2.3%)

Hyperbilirubinemia

5 (16.7%)

2 (15.4%)

7 (16.3%)

Grade 1

1 (3.3%)

1 (7.7%)

2 (4.7%)

Grade 2

1 (7.7%)

1 (2.3%)

Grade 3

4 (13.3%)

4 (9.3%)

Grade 4

Transaminitis

16 (53.3%)

7 (53.8%)

23 (53.5%)

Grade 1

2 (6.7%)

1 (7.7%)

3 (7.0%)

Grade 2

4 (13.3%)

4 (9.3%)

Grade 3

6 (20.0%)

6 (46.2%)

12 (27.9%)

Grade 4

4 (13.3%)

4 (9.3%)

Febrile neutropenia

24 (80.0%)

12 (92.3%)

36 (83.7%)

Encephalopathy (grade 2)

1 (100%)

1 (2.3%)

Renal and urinary disorders

Acute kidney injury (grade 2)

2 (15.4%)

2 (4.7%)

Infections and infestations

Bacterial infections

17 (56.7%)

8 (61.5%)

25 (58.1%)

Viral infections

5 (16.7%)

1 (7.7%)

6 (14.0%)

Fungal infections

8 (26.7%)

4 (30.8%)

12 (27.9%)

Sepsis (NOS)

9 (30.0%)

4 (30.8%)

13 (30.2%)

ICU admissions

13 (43.3%)

6 (46.2%)

19 (44.2%)

**Table 4.** Hematopoietic Stem Cell Transplant-Related Parameters and Outcome
	ALL (30, 69.8%)	AML (13, 30.2%)	Total (43,100%)
Values are presented as numbers (percentage). TBI: total body irradiation; Flu: fludarabine; Bu: Busulfan; Cy: cyclophosphamide; MTX: methotrexate; ATG: antithymocyte globulin; CSA: cyclosporine; MMF: mycophenolate mofetil; ALL: acute lymphoblastic leukemia; AML: acute myeloid leukemia; GVHD: graft-versus-host disease; ANC: absolute neutrophil count.
Transplanted	11 (36.7%)	7 (53.8%)	18 (41.9%)
Time to transplant from clofarabine cycle 1	2.7 (1.2 - 6.4)	2.6 (1.4 - 5.3)	2.7 (1.2 - 6.4)
Donor type
Matched related	9 (81.9%)	6 (85.7%)	15 (83.3%)
Haploidentical	2 (18.2%)	1 (14.3%)	3 (16.7%)
GVHD prophylaxis
CSA, MTX ± ATG	7 (63.6%)	5 (71.4%)	12
CSA, MMF ± Cy	2 (18.2%)	1 (14.3%)	3
MMF, Cy	1 (9.1%)	1 (14.3%)	2
MTX	1 (9.1%)	-	1
Conditioning regimen
Bu, Cy	-	2 (28.6%)	2
Bu, Cy, VP-16	1 (9.1%)	-	1
Cy, ATG, TBI	1 (9.1%)	-	None
Cy, TBI	6 (54.5%)	3 (42.9%)	9
Flu, Cy, TBI	1 (9.1%)	-	1
Flu, TBI	1 (9.1%)	1 (14.3%)	2
Thiotepa, Flu, TBI	1 (9.1%)	1 (14.3%)	2
Time to ANC engraftment, days, median (range)	16 (13 - 38), n = 11	19 (13 - 26), n = 5	17 (13 - 38), n = 16
Time to ANC engraftment, days, median (range)	23 (14 - 96), n = 9	22 (20 - 26), n = 5	22.5 (14 - 96), n = 14
Acute GVHD (+)	3 of 11 (27.3%)	2 of 7 (28.6%)	5 of 18 (27.8%)
Skin	3	1	4
Liver	1	-	1
Gut	1	1	2
Transplant related toxicity (within day + 100)
Mucositis	5 (45.5%)	1 (14.3%)	6 (33.3%)
Interstitial pneumonia	1 (9.1%)	1 (14.3%)	2 (11.1%)
Infections
Bacterial	3 (27.3%)	3 (42.9%)	6 (33.3%)
Viral	7 (63.6%)	1 (14.3%)	8 (44.4%)
Fungal	-	-	None
Seizures	-	-	None
Veno-occlusive disease	1 (9.1%)	-	1 (5.6%)
Hemorrhagic cystitis	3 (27.3%)	-	3 (16.7%)

Table 4. Hematopoietic Stem Cell Transplant-Related Parameters and Outcome

ALL (30, 69.8%)

AML (13, 30.2%)

Total (43,100%)

Values are presented as numbers (percentage). TBI: total body irradiation; Flu: fludarabine; Bu: Busulfan; Cy: cyclophosphamide; MTX: methotrexate; ATG: antithymocyte globulin; CSA: cyclosporine; MMF: mycophenolate mofetil; ALL: acute lymphoblastic leukemia; AML: acute myeloid leukemia; GVHD: graft-versus-host disease; ANC: absolute neutrophil count.

Transplanted

11 (36.7%)

7 (53.8%)

18 (41.9%)

Time to transplant from clofarabine cycle 1

2.7 (1.2 - 6.4)

2.6 (1.4 - 5.3)

2.7 (1.2 - 6.4)

Donor type

Matched related

9 (81.9%)

6 (85.7%)

15 (83.3%)

Haploidentical

2 (18.2%)

1 (14.3%)

3 (16.7%)

GVHD prophylaxis

CSA, MTX ± ATG

7 (63.6%)

5 (71.4%)

CSA, MMF ± Cy

2 (18.2%)

1 (14.3%)

MMF, Cy

1 (9.1%)

1 (14.3%)

MTX

1 (9.1%)

Conditioning regimen

Bu, Cy

2 (28.6%)

Bu, Cy, VP-16

1 (9.1%)

Cy, ATG, TBI

1 (9.1%)

None

Cy, TBI

6 (54.5%)

3 (42.9%)

Flu, Cy, TBI

1 (9.1%)

Flu, TBI

1 (9.1%)

1 (14.3%)

Thiotepa, Flu, TBI

1 (9.1%)

1 (14.3%)

Time to ANC engraftment, days, median (range)

16 (13 - 38), n = 11

19 (13 - 26), n = 5

17 (13 - 38), n = 16

Time to ANC engraftment, days, median (range)

23 (14 - 96), n = 9

22 (20 - 26), n = 5

22.5 (14 - 96), n = 14

Acute GVHD (+)

3 of 11 (27.3%)

2 of 7 (28.6%)

5 of 18 (27.8%)

Skin

Liver

Gut

Transplant related toxicity (within day + 100)

Mucositis

5 (45.5%)

1 (14.3%)

6 (33.3%)

Interstitial pneumonia

1 (9.1%)

1 (14.3%)

2 (11.1%)

Infections

Bacterial

3 (27.3%)

3 (42.9%)

6 (33.3%)

Viral

7 (63.6%)

1 (14.3%)

8 (44.4%)

Fungal

None

Seizures

None

Veno-occlusive disease

1 (9.1%)

1 (5.6%)

Hemorrhagic cystitis

3 (27.3%)

3 (16.7%)