scholarly journals B-cell acute lymphoblastic leukemia as a secondary malignancy following diffuse large B-cell lymphoma

2019 ◽  
Vol 11 (2) ◽  
Author(s):  
Daria Gaut ◽  
Anthony Bejjani ◽  
Joshua Sasine ◽  
Gary Schiller

Secondary acute lymphoblastic leukemia (ALL) is a rare disease that has not been well characterized compared with secondary myelodysplastic syndrome or secondary acute myeloid leukemia. We present a report of two patients who developed ALL following complete remission of diffuse large B-cell lymphoma (DLBCL). The first case is more consistent with a therapy-related ALL as a PCR analysis of bone marrow aspirate revealed a distinct clone and the mixed-lineage leukemia gene rearrangement, commonly associated with exposure to topoisomerase II inhibitors. The second case is more consistent with clonal evolution given positive MYC and BCL2 fusion signals in the original diagnosis of DLBCL and the secondary ALL.

Author(s):  
Karen Thudium Mueller ◽  
Stephan A. Grupp ◽  
Shannon L. Maude ◽  
John E Levine ◽  
Michael A Pulsipher ◽  
...  

Tisagenlecleucel is indicated for pediatric and young adult patients with relapsed/refractory (r/r) B-cell acute lymphoblastic leukemia (B-ALL) and adult patients with r/r diffuse large B-cell lymphoma (DLBCL). The tisagenlecleucel chimeric antigen receptor (CAR) contains a murine single-chain variable fragment domain; hence, we examined the effects of humoral and cellular immune responses to tisagenlecleucel on clinical outcomes using 2 validated assays. Data were pooled from ELIANA (NCT02435849) and ENSIGN (NCT02228096) trials in r/r B-ALL (N=143) and the JULIET trial (NCT02445248) in r/r DLBCL (N=115). Humoral responses were determined by flow cytometric measurement of anti-murine CAR19 (mCAR19) antibodies in serum. Cellular responses were determined using T-cell production of interferon gamma in response to 2 different pools of mCAR19 peptides. Pretreatment anti-mCAR19 antibodies were detected in 81% of patients with r/r B-ALL and 94% of patients with r/r DLBCL. Posttreatment anti-mCAR19 antibodies were higher than patient-specific baseline in 42% of r/r B-ALL and 9% of r/r DLBCL patients. Pretreatment and posttreatment anti-mCAR19 antibodies did not affect tisagenlecleucel cellular kinetics including Cmax and persistence (r2<0.05), clinical response (day 28 response, duration of response, event-free survival), or safety. T-cell responses were consistent over time, with net responses <1% at baseline and posttreatment time points in the majority of patients with no effect on transgene expansion and persistence or outcomes. Presence of baseline and/or posttreatment anti-mCAR19 antibodies or T-cell responses did not alter the activity of tisagenlecleucel in patients with r/r B-ALL or r/r DLBCL.


2007 ◽  
Vol 48 (2) ◽  
pp. 230-232
Author(s):  
Itaru Kato ◽  
Atsushi Manabe ◽  
Chiaki Aoyama ◽  
Takahiro Kamiya ◽  
Tsuyoshi Morimoto ◽  
...  

2019 ◽  
Vol 39 (6) ◽  
pp. 592-595 ◽  
Author(s):  
David Buchbinder ◽  
Ivan Kirov ◽  
Jeffrey Danielson ◽  
Nirali N. Shah ◽  
Alexandra F. Freeman ◽  
...  

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