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ctt-journal > Paina et al. (Abstract)

Paina et al. (Abstract)

Cellular Therapy and Transplantation (CTT), Vol. 3, No. 12
doi: 10.3205/ctt-2011-No12-abstract60

© The Authors. This abstract is provided under the following license: Creative Commons Attribution 3.0 Unported

Abstract accepted for "5th Raisa Gorbacheva Memorial Meeting Hematopoietic Stem Cell Transplantation in Children and Adults", Saint Petersburg, Russia, September 18–20, 2011

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Use of haploidentical stem-cell transplantation with KIR mismatch as salvage therapy for poor-risk acute leukemia

Olesya V. Paina, Elena V. Babenko, Alla A. Golovacheva, Alexander L. Alyanskiy, Elena V. Semenova, Natalia V. Stancheva, Igor A. Lisukov, Ludmila S. Zubarovskaya, Boris V. Afanasyev

R.M. Gorbacheva Memorial Institute of Children Hematology and Transplantation, St. Petersburg Pavlov State Medical University, St. Petersburg, Russia

Correspondence: Olesya V. Paina, R.M. Gorbacheva Memorial Institute of Children Hematology and Transplantation, St. Petersburg Pavlov State Medical University, 6/8, Tolstoy str., St. Petersburg, 197022, Russia, E-mail: paina@spam is badmail.ru

Abstract

Introduction: Haploidentical hematopoietic stem cell transplantation (haplo-HSCT) has made tremendous progress over the past 20 years and has become a feasible option for leukemia patients without HLA-matched related or unrelated donors. The early complications including severe acute graft-versus-host disease (aGVHD), graft failure, delayed engraftment and in addition, disease recurrence, have limited the usage of this approach. NK-cell alloreactivity is determined by the presence in the donor of NK cells expressing inhibitory killer cell Ig-like receptors (KIRs) that recognize HLA class I allotypes present in the donor but lacking in the recipient. This phenomenon can improve event-free survival (EFS) after haplo-HSCT, especially in AML patients.   

Aim: To compare the efficacy of KIR-ligand mismatched and matched haplo-HSCT in patients with very high risk of acute lymphoblastic or myeloid leukemia.

Methods: Twenty-one children and adolescents with hematological malignancies were included in the study. Details on patient and donor characteristics are reported in Table 1. The median number of infused CD34+ cells was 8.9×106 (range 3.9–25.8) per kg b.w. Children with evidence of donor engraftment who survived more than 14 days and more than 90 days from transplantation were evaluated for occurrence of aGVHD and chronic GVHD, respectively, according to established criteria.

Table 1. Patient, donor, and graft characteristics

Case

Sex

Age at Tx

Diagnosis

Disease status at Tx

Donor

No of CD34+ cells infused (x106/kg)

No of CD3+ cells infused (x107/kg)

KIR-ligand-mismatched (GvH dir.)

aGvHD

chGvHD

Outcome

1

M

4

ALL

Relapse

Father

14

n.e

Yes

Grade II

Limited

Alive (+542 days)

2

F

6

ALL

Resistant

Mother

7.5

n.e

Yes

Grade II

Extensive

Alive (+575 days)

3

F

7

ALL

CR 1

Father

12.2

n.e

No

No

Limited

Alive (+513 days, relapse)

4

F

2

ALL

Resistant

Mother

25.8

n.e

Yes

Grade I

n.e.

Dead (+30 days, relapse)

5

M

19

ALL

Resistant

Father

6.4

3.2

Yes

No

n.e.

Dead (+17 days, rejection)

6

F

1

ALL

Relapse

Mother

12.9

n.e

Yes

Grade II

Extensive

Alive (+465 days)

7

M

5

ALL

Relapse

Mother

7.4

11

Yes

Grade III

Extensive

Alive (+420 days)

8

F

19

ALL

Relapse

Father

6.7

n.e

Yes

n.e.

n.e.

Dead (+7days, relapse)

9

F

2

ALL

Relapse

Father

20

5

No

No

n.e.

Dead (+33days, relapse)

10

F

16

ALL

Resistant

Mother

5.1

n.e

No

Grade IV

n.e.

Dead (+128days, aGvHD)

11

F

15

AML

Resistant

Brother

4

n.e

No

n.e.

n.e.

Dead (+30 days, rejection)

12

F

18

AML

Resistant

Mother

10

n.e

No

Grade IV

n.e.

Dead (+21 days, aGvHD)

13

F

8

ALL

Resistant

Father

14

1.2

No

n.e.

n.e.

Dead (+31 days, relapse)

14

F

8

ALL

Relapse

Mother

4.8

2.4

No

n.e.

n.e.

Dead (+73 days, relapse)

15

M

9

ALL

Resistant

Mother

4.5

n.e

Yes

n.e.

n.e.

Dead (+121 days, aGvHD)

16

M

17

AML

Resistant

Mother

6.1

4.31

No

No

n.e.

Dead (+158 days, relapse)

17

M

30

AML

Resistant

Mother

7

1.8

Yes

Grade II

Limited

Alive (+304)

18

F

22

AML

Relapse

Mother

3.9

3.41

No

n.e.

n.e.

Dead (+69 days, rejection)

19

M

27

AML

CR 2or>

Sister

1.83

11.9

No

No

n.e.

Alive (+217 days, relapse)

20

M

9

ALL

CR 2or>

Father

4.5

n.e

No

Grade IV

n.e.

Dead (+58 days, aGvHD)

21

M

12

ALL

Resistant

Father

8.24

5.5

Yes

n.e.

n.e.

Dead (+62 days, relapse)

F, female; M, male; Tx, transplantation; ALL, acute lymphoblastic leukemia; AML, acute myeloid leukemia; CR, complete remission; GVHD, graft-versus-host disease; n.e, not evaluable

Cell Ther Transplant. Vol. 3, No. 12. doi:10.3205/ctt-2011-No12-abstract60-table1


Results:
One-year overall survival (OS) and EFS were higher in patients after KIR-ligand mismatched haplo-HSCT compared with KIR-ligand matched haplo-HSCT: 50% and 50% vs. 27% and 18% respectively. NK-alloreactivity increases OS in very high risk ALL patients to 44.4% vs. 16.7%; EFS was 33.3% vs 0%. aGVHD developed in 9 pts (43%), but it was not the main reason of mortality (III–IV stage in 4 pts, 19%).

Conclusions: Haplo-HSCT is effective as salvage therapy for patients with very high-risk acute leukemia. The main reason for treatment failure after haplo-HSCT remains relapse, which requires continuing therapy by immunotherapy with/without chemotherapy.

Figure 1. OS after haplo-HSCT in acute leukemia patients; Figure 2. OS after haplo-HSCT in ALL patients

Keywords: haploidentical HSCT, KIR-ligand mismatched

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