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addition of thiotepa to the conditioning regimen significantly improves transplant outcomes in children undergoing cord blood transplantation for non malignant disease lurie children s hospital of chicago s experience

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Tiêu đề Addition of Thiotepa to the Conditioning Regimen Significantly Improves Transplant Outcomes in Children Undergoing Cord Blood Transplantation for Non-Malignant Disease
Tác giả Mehboob Merchant, Reggie E. Duerst, Alfred Rademaker, Morris Kletzel
Trường học Northwestern University Feinberg School of Medicine
Chuyên ngành Hematology/Oncology/Pediatric Transplantation
Thể loại research article
Năm xuất bản 2014
Thành phố Chicago
Định dạng
Số trang 2
Dung lượng 171,45 KB

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361 Addition Of Thiotepa To The Conditioning Regimen Significantly Improves Transplant Outcomes In Children Undergoing Cord Blood Transplantation For Non-Malignant Disease.. 1Mathews’ Cen

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disease prophylaxis was Tacrolimus/Methotrexate in FIC

re-cipients and Tacrolimus/Mycophenolate in RIC rere-cipients

Additionally, all the patients received thymoglobulin 1.5 mg/

Kg on day -3, -2 and -1 All patients received peripheral stem

cells except one patient with mismatch MD who received

bone marrow product

Results: Patient Characteristics are shown in Table 1 All the

patient engrafted except one who received marrow product

All the patients but 3 (8%) achieved 90% or more donor

chimerism by day 100 With Mean follow up of 500 days

(range, 100-1242) the overall survival (OS) was 77% 7 (CI

63-91%) at 1 year and 67% 9 (CI 49-85%) at 2 years

Simi-larly, disease free survival was 66%8 (CI 50-82%) at 1 and 2

years Cumulative incidence of acute GVHD grade II-IV was

55% with grade III-IV 12% Cumulative incidence of chronic

GVHD at 1 year was 43% with extensive chronic GVHD in 17%

The regimen was associated with low treatment related

mortality (TRM) with cumulative incidence of only 5% at one

year, CI 14-21% The cumulative incidence of relapse at one

year was 29%, CI 17-49% On univariate analysis only high risk

CIBMTR status was predictive of poor OS (p¼0.05)

Conclusion: The addition of low dose thymoglobulin to RIC

and FIC regimens with iv Busulfan/Fludarabine prior to MUD

HCT results in low TRM and improved OS for patients with

AML/MDS Relapse rate does not seem to be increased in this

cohort by the addition of low dose thymoglobulin in

com-parison to historical control

361 Addition Of Thiotepa To The Conditioning Regimen

Significantly Improves Transplant Outcomes In Children

Undergoing Cord Blood Transplantation For

Non-Malignant Disease Lurie Children’s Hospital Of Chicago’s

Experience

Mehboob Merchant1, Reggie E Duerst2,3,4, Alfred Rademaker5,

Morris Kletzel1,4,6,7 1Mathews’ Center for Cellular Therapy,

Northwestern Memorial Hospital, Chicago, IL;2Feinberg School

of Medicine, Northwestern University, Chicago, IL;3Ann & Robert H Lurie Children’s Hospital of Chicago, Chicago, IL;

4Robert H Lurie Comprehensive Cancer Center, Northwestern University, Chicago, IL;5Biostatistics Collaboration Center, Northwestern University Feinberg School of Medicine, Chicago, IL;6Pediatrics, Northwestern University Feinberg School of Medicine, Chicago, IL;7Hematology, Oncology, Transplant, Ann

& Robert H Lurie Children’s Hospital of Chicago, Chicago, IL

We retrospectively evaluated all CBT performed for non-malignant conditions to determine if there is any correlation between transplant outcomes & conditioning, including Total body irradiation, Fludarabine, Cyclophosphamide, Etoposide

& Thiotepa

Between 1/1995 & 1/2011, 50 CBT were performed Condi-tioning: TBI + VP16 + Cy (11); TBI + TT VP16 + Cy (4); TT + FLUD Bu  VP16 (6); Bu + Cy (11); Bu + FLUD (15); VP + Cy (2); no conditioning (1) Diagnoses: Immunodeficiency (22),

BM failure (10), Metabolic disease (6), Histiocytic disease (6), Hemoglobinopathy (6)

There were 20 F, 30 M Median age 1.0 yr (0.1e 17.4), wt 9.15

kg (3.0 - 52.0) HLA match: 6/6 (7), 5/6 (13), 4/6 (27), 3/6 (3) Median cell dose/Kg: TNC 0.89ˇ8, MNC 0.77ˇ8, CD34 0.99ˇ6 CBU were processed per Rubenstein et al GvHD prophylaxis: MTX + ATG + CSA (18); MMF + ATG + CSA (13); no MTX/MMF (19); PRED or FK506 (10)

Statistical analyses were done using Fisher’s Exact, Log-Rank, & Column stats Significance was determined at p-value of 0.05 Overall Results: 62% achieved ANC>500 cells/mL at 20 days (11 - 40); 56% had PLT>20,000 at 40 d (14 - 100); & 52% achieved>95% chimerism at 43 d (13 - 169) 13 pts died from day + 100 TRM 30 pts are survivors at this time EFS> 1, 3, 5 yr was 44, 32 & 30%, with OS of 62, 46 & 42% 8 pts are event free

>10 yr Median follow up was 2.0 yr (0.2- 14.6 yr) Acute GVHD grade II - IV was seen in 12, there was no chronic GVHD Conclusion: In this cohort patients who received Thiotepa in addition to other conditioning showed statistically signi fi-cant transplant outcomes There was no TRM 5 yr OS was 100%, EFS 90% Thiotepa recipients had better and rapid

Diagnosis

HLA

Conditioning Regimen

Status at transplant

CIBMTR risk

Cytogenetic risk

CR¼complete remission, PIF¼ primary refractory

Table 1 Group Variables.

Infused TNC/kg 8 1.21 0.37- 3.18 0.85 0.05- 4.27 0.52 Infused MNC/kg 8 1.06 0.31- 2.83 0.73 0.04- 3.84 0.49 Infused CD34/kg 6 0.83 0.10- 8.7 0.99 0.02- 7.6 0.31

HLA Match 3/6, 4/6, 5/6, 6/6

0, 5,

5, 0

0, 50, 50, 0 3, 22,

8,7

8, 55, 20, 17 0.20

Table 2 Group Outcomes.

(40)

P-value

Abstracts / Biol Blood Marrow Transplant 20 (2014) S211eS256 S234

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chimerism, and the engraftment percent were statistically

significant No other statistical significance was seen

be-tween the two groups with respect to age, HLA match, cell

dose, aGVHD, or TBI or other conditioning In conclusion,

addition of Thiotepa to conditioning regimen dramatically

changes transplant outcomes of pediatric non malignancy

patients undergoing cord blood transplantation

362 Increased Transplant Related Mortality and Poor Donor

Cell Chimerism in African American Children Undergoing

Umbilical Cord Blood Transplantation Institutional

Experience at Lurie Children’s Hospital of Chicago

Mehboob Merchant1, Reggie E Duerst2,3,4, Alfred Rademaker5,

Morris Kletzel1,3,6,7 1Mathews’ Center for Cellular Therapy,

Northwestern Memorial Hospital, Chicago, IL;2Ann & Robert

H Lurie Children’s Hospital of Chicago, Chicago, IL;3Robert H

Lurie Comprehensive Cancer Center, Northwestern University,

Chicago, IL;4Feinberg School of Medicine, Northwestern

University, Chicago, IL;5Biostatistics Collaboration Center,

Northwestern University Feinberg School of Medicine, Chicago,

IL;6Pediatrics, Northwestern University Feinberg School of

Medicine, Chicago, IL;7Hematology, Oncology, Transplant, Ann

& Robert H Lurie Children’s Hospital of Chicago, Chicago, IL

We retrospectively evaluated all CBT to see if there is a cor-relation between patient ethnicity & transplant outcomes Between 1/1995 & 1/2011 we performed 145 CBT for the treatment of malignant (95), non-malignant (50) conditions Conditioning regimen: TBI + VP16 + Cy (79); TBI + TT + VP16 +

Cy (16); Bu Cy  FLUD (31); Cy  TT or VP16 (12); other combinations (20)

Malignancies: ALL (47), AML (29), other (19); Pt status: PR (7), CR1 (39), CR2 (42), CR3 (7)

Non-malignancies: Immunodeficiency (22); BM failure (10); Metabolic (6); Histiocytic (6); Hemoglobinopathy (6) Cohort was 65 F, 80 M; median age 3.8 yr (0.1 - 20.6), wt 15.5

kg (3.0 - 73.0)

Ethnicity: Caucasian (52), Hispanic (44), African American (31), Asian (13), Mid Eastern (5)

HLA match: 6/6 (15), 5/6 (38), 4/6 (83), 3/6 (9)

Median cell dose/Kg: 0.64ˇ8 TNC, 0.56ˇ8 MNC & 0.70ˇ6 CD34 GvHD prophylaxis: MTX + ATG + CSA/FK506 PRED (92); MMF + ATG + CSA (16); CSA/FK506 + ATG PRED (37) Statistical analyses were done using Fisher’s Exact and log-rank tests, column stats, and T- test Significance was deter-mined at p-value of 0.05

Overall Outcomes: ANC>500 cells/mL was achieved in 70.3%

of pts at 23 days (1 - 60); 66.2% achieved PLT count of

>20,000 at 42 days (14 - 100); and 64.8% achieved >95%

Figure K-M.

Table 1

Group Variables.

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