Ajoy Dias 1, Hassan B. Alkhateeb 1, Nosha Farhadfar 2,. Shahrukh K. Hashmi 1, Aref Al-Kali 3, William J. Hogan 1,. Mrinal S. Patnaik 4, Linda J. ... Rochester, Rochester, MN; 3 200 1st Street SW, Mayo Clinic. Rochester, Rochester, MN; 4 ...
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Abstracts / Biol Blood Marrow Transplant 22 (2016) S19eS481
Figure 2 BIBLIOGRAPHY
464 Inversion (3) in an Allogeneic Stem Cell Transplant Recipient Representative of a Donor Derived Constitutional Abnormality- a Unique Case Report Ajoy Dias 1, Hassan B. Alkhateeb 1, Nosha Farhadfar 2, Shahrukh K. Hashmi 1, Aref Al-Kali 3, William J. Hogan 1, Mrinal S. Patnaik 4, Linda J. Burns 5, Daniel Van Dyke 6, Dietger Niederwieser 7, Mark R. Litzow 1. 1 Division of Hematology, Mayo Clinic, Rochester, MN; 2 Mayo Clinic Rochester, Rochester, MN; 3 200 1st Street SW, Mayo Clinic Rochester, Rochester, MN; 4 Division of Hematology, Mayo Clinic Rochester, Rochester, MN; 5 National Marrow Donor Program/Be The Match, Minneapolis, MN; 6 Mayo Clinic Cytogenetics Laboratory, Mayo Clinic Rochester, Rochester, MN; 7 Division of Haematology & Oncology, University of Leipzig, Leipzig, Germany Introduction: Hematopoietic stem cell transplantation (HSCT) is an important treatment for hematological malignancies. It can be associated with severe complications including relapse and treatment related toxicities. Donor evaluation with chromosome analysis remains controversial. There are reports of the transmission of constitutional karyotypic abnormalities from donor to recipient after HSCT. Here we report the identification of a constitutional inv (3) (p21.3q26.2) chromosomal abnormality transmitted to an adult patient with acute myeloid leukemia (AML) from a matched unrelated donor after allogeneic HSCT. Case Description: A 54 year old white male diagnosed with Polycythemia Vera (JAK2 Kinase mutation positive) in January 2012 was managed with therapeutic phlebotomy and hydroxyurea. In July 2014 he transformed to AML with bone marrow showing 70% blasts and a diploid karyotype. After induction chemotherapy with 7+3 and nilotinib on a clinical trial he had residual disease on day 14 and was reinduced with 7+3, nilotinib and consolidated with high dose cytarabine with nilotinib and attained a CR. Following myeloablative conditioning with busulfan and cyclophosphamide he received stem cells from a German donor in November 2014. In February 2015 his bone marrow biopsy showed no morphologic leukemia and chimerisms were 100% donor DNA. Cytogenetic analysis showed diploid karyotype with each metaphase having a balanced inv (3) (p26q25) abnormality, confirmed on congenital chromosome analysis of peripheral blood. His donor’s bone marrow evaluation demonstrated diploid cytogenetics with inv (3) (p21.3q26.2), each metaphase having an apparently balanced pericentric inversion of chromosome 3.
1 Niederwieser D GC, Hegenbart U: Transmission of donor illness by stem cell transplantation: should screening be different in older donor? Bone Marrow Transplant 34:657-65, 2004 2 Loh J C CD, Grody WW, Chiu MW: A case of mycosis fungoides transmitted from donor to recipient and review of literature of T cell malignancies after transplantation. Clinical Lymphoma, Myeloma and Leukemia 14:e137-140, 2014
Discussion: Reports of transmission of donor malignancy in BMT are extremely rare in the literature1. A few have reported transmission of hematological malignancies after hematopoietic stem cell transplantation2. In addition to malignancies, nonmalignant molecular aberrations are also reported after allogeneic stem cell transplantation. These include balanced translocation rearrangements such as Robertsonian translocations, reciprocal translocations and inversions. One in 175 to 250 phenotypically normal subjects carries a balanced rearrangement. Our case reports the cytogenetic abnormality inv (3) (p21.1q26.2) three months after transplantation. Conclusion: This is the first case report of inv (3) transmitted from the donor. Our main aim is to increase awareness of transmission of common cytogenetic abnormalities. No untoward clinical outcomes have been reported thus far. Please see figure1 listing NMDP reported Cytogenetic abnormalities from 1990-2010.
465 Cytomegalovirus Reactivation after Umbilical Cord Transplantation and Its Impact on Outcomes- a Mayo Clinic Experience Ajoy Dias 1, Hassan B. Alkhateeb 1, Nosha Farhadfar 2, Gustavo Westin 2, Shahrukh K. Hashmi 1, Mark R. Litzow 1, Mrinal S. Patnaik 3, Raymund Razonable 4, William J. Hogan 1. 1 Division of Hematology, Mayo Clinic, Rochester, MN; 2 Mayo Clinic Rochester, Rochester, MN; 3 Division of Hematology, Mayo Clinic Rochester, Rochester, MN; 4 Division of Infectious Disease, Mayo Clinic, Rochester, MN Background: Umbilical cord blood transplantation (UCBT) is an alternative for patients with hematologic diseases who lack a matched related or unrelated donor. One disadvantage is delayed immune reconstitution with anticipated increased
Figure 1 NMDP reported Cytogenetic abnormalities front 1990-2010 of hematological malignancies and non-malignant chromosomal abnormalities. Year
Recipient data
Donor data
Reported CG abnormality/malignancy
Aug-06 Sep-07 Nov-07 Dec-07 Mar-08 Jun-08 Sep-08 Oct-08 Apr-10 Jun-10
Trisomy 8 mosaicism Klinefelter syndrome t( 13;21) Same translocation t(9;12) Donor found to have inv(10) Mantle cell lymphoma Ph+ translocation t(9;22) (q34;q11). t(18;21) (q21;p11.2) t(X;2) Donor found to have same translocation
Trisomy 8 Klinefelter syndrome t(13;21) t(9;12) inv(10) Mantle cell lymphoma t(9;22)(q34;q11) t(18;21) (q21;p11.2) t(X;2) t(13;16) (q14;22)
Sep-10
Trisomy 8 Klinefelter syndrome t(13;21) New translocation t(9;12) New inv(10) on bone marrow biopsy Mantle cell lymphoma - primary diagnosis CML BCR-ABL by FISH; Primary diagnosis: MDS t(18;21) (q21;p11.2) Balanced translocation; t(X;2) New translocation between long arms of chromosomes 13 and 16 at bands ql4 and q22 Female recipient was found to have karyotype XXY
XXY- Klinefelter syndrome
Oct-10
Increased genetic material on chromosome 13 and 15
Marrow and peripheral blood had karyotype XXY Chromosomal abnormalities on 13 and 15
OG abnormality on chromosome 13 and 15
Abstracts / Biol Blood Marrow Transplant 22 (2016) S19eS481
risk of infections including cytomegalovirus (CMV). Our study was aimed: $ To assess incidence of CMV reactivation after UCBT $ To evaluate the effect of CMV reactivation on neutrophil, lymphocyte and platelet engraftment $ To assess the impact of CMV reactivation on outcomes Methods: After IRB approval, adults who underwent HLAmatched UCBT during 2011 and 2014 were queried. All grafts were T-cell replete. Relapse incidence (RI), non-relapse mortality (NRM), and overall survival (OS) were compared according to CMV reactivation status. CMV reactivation was defined as positive CMV PCR test (>137 IU/ml) during the first 100 days post UCBT. Statistical comparisons used c2 test for categorical variables and Wilcoxon test for continuous variables. Kaplan-Meier and log rank test analyzed survival. Cumulative incidence of RI and NRM were analyzed as competing events, using Gray’s test. Results: Forty-three pts who underwent 4/6 HLA matched UCBT were identified. The median age at transplant was 50 (19-64) and 23(53%) were male. 25 (58%) pts had a diagnosis of AML. Median follow up was 360 days (30-1587) at which 22(51%) deaths occurred, 27% were related to relapse. All patients received GVHD prophylaxis with cyclosporine and mycophenolate mofetil. Patient characteristics based on recipient CMV status detailed in Table1. Thirty-three (77%) had CMV reactivation in the whole cohort, with incidence of 61% in CMV seropositive and 1(10%) in CMV seronegative patients (p 0.0056). All were treated with IV ganciclovir or valganciclovir. None developed CMV disease. Median overall survival for CMV negative recipient was NR (1.3-NR), compared to 17.3 months (7.6-NR) in CMV positive recipient (p 0.36). RI and NRM were not statistically different (p 0.36 & 0.61 respectively) (Figure1). Conclusion: CMV reactivation was common after UCBT, especially among CMV seropositive patients. However, it did not impact engraftment, RI, NRM or OS. This could be due to aggressive treatment of CMV infection.
Table 1 Patient Characteristics VARIABLE
CMV POSITTVE (N33)
Male 19(58%) Age 50(19-63) Diagnosis Acute Mveloid Leukemia 22(67%) Acute Lymphocytic 5(15%) Leukemia Mvelodvsplastic 5(15%) Syndrome Other* 1(3%) Conditioning Regimen FCvTBI¼0 27(82%) FCy/ATG TBI¼3 3(9%) CvTBI¼4 3(9%) Days to Engraftment Neutrophils 25(14-76) Platelet 41(24-144) Lvmphocvte 26.5(13-83) CMY Reactivation 20 (61%)
CMV NEGATIVE CN10)
P value
4(40%) 41(20-64)
0.32 0.26
3(30%) 1(10%)
0.05
3(30%) 3(30%) 8(80%) 2(20%)
24.5(17-33) 41(26-97) 24(15-60) 1(10)
0.31
0.63 0.67 0.21 0.0056
KEY: F¼Fludarabine, Cy¼Cyclophosphamide, TBI¼ total body irradiation, ATG¼ Ant Antitymocyte globulin, GVH¼ Graft versus host disease, *1 Multiple myeloma, 1 Chronic lymphatic leukemia, 1 T cell lymphoma, 1 PNH AA
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