Abstract
Initial treatment with the monoclonal anti-CD52 antibody alemtuzumab induces responses in the majority of patients with T-cell prolymphocytic leukemia (T-PLL). In eligible patients, allogeneic hematopoietic stem cell transplantation (allo-HSCT) is an option to consolidate hematological remissions. Here, we report our experience with 10 patients who received allo-HSCT against T-PLL. Notably, 3 patients with complete remission at transplantation and durable full-donor chimerism relapsed at months 12, 59, and 84 after transplantation, respectively. This relapse was associated with rapid progressive leukemia in 1 patient and extralymphatic lymphoma growth in the other 2. Despite CD52 positivity at relapse, alemtuzumab retreatment, donor lymphocyte infusions, and/or chemotherapy including salvage therapy, allo-HSCT yielded a transient partial response, only. Alemtuzumab induction and consolidative allo-HSCT enabled prolonged disease-free survival in these patients but failed to procure cure.
References
1.
Matutes
E
, Brito-Babapulle
V
, Swansbury
J
, Ellis
J
, Morilla
R
, Dearden
C
, et al. Clinical and laboratory features of 78 cases of T-prolymphocytic leukemia
. Blood
. 1991
Dec
;78
(12
):3269
–74
.
[PubMed]
0006-49712.
3.
Soulier
J
, Pierron
G
, Vecchione
D
, Garand
R
, Brizard
F
, Sigaux
F
, et al. A complex pattern of recurrent chromosomal losses and gains in T-cell prolymphocytic leukemia
. Genes Chromosomes Cancer
. 2001
Jul
;31
(3
):248
–54
.
[PubMed]
1045-22574.
Stoppa-Lyonnet
D
, Soulier
J
, Laugé
A
, Dastot
H
, Garand
R
, Sigaux
F
, et al. Inactivation of the ATM gene in T-cell prolymphocytic leukemias
. Blood
. 1998
May
;91
(10
):3920
–6
.
[PubMed]
0006-49715.
Yamaguchi
M
, Yamamoto
K
, Miki
T
, Mizutani
S
, Miura
O
: T-cell prolymphocytic leukemia with der(11)t(1;11)(q21;q23) and ATM deficiency. 2003
.6.
Maljaei
SH
, Brito-Babapulle
V
, Hiorns
LR
, Catovsky
D
. Abnormalities of chromosomes 8, 11, 14, and X in T-prolymphocytic leukemia studied by fluorescence in situ hybridization
. Cancer Genet Cytogenet
. 1998
Jun
;103
(2
):110
–6
.
[PubMed]
0165-46087.
Bergmann
AK
, Schneppenheim
S
, Seifert
M
, Betts
MJ
, Haake
A
, Lopez
C
, et al. Recurrent mutation of JAK3 in T-cell prolymphocytic leukemia
. Genes Chromosomes Cancer
. 2014
Apr
;53
(4
):309
–16
.
[PubMed]
1045-22578.
Stengel
A
, Kern
W
, Zenger
M
, Perglerová
K
, Schnittger
S
, Haferlach
T
, et al. Genetic characterization of T-PLL reveals two major biologic subgroups and JAK3 mutations as prognostic marker
. Genes Chromosomes Cancer
. 2016
Jan
;55
(1
):82
–94
.
[PubMed]
1045-22579.
López
C
, Bergmann
AK
, Paul
U
, Murga Penas
EM
, Nagel
I
, Betts
MJ
, et al. Genes encoding members of the JAK-STAT pathway or epigenetic regulators are recurrently mutated in T-cell prolymphocytic leukaemia
. Br J Haematol
. 2016
Apr
;173
(2
):265
–73
.
[PubMed]
0007-104810.
Staber
PB
, Herling
M
, Bellido
M
, Jacobsen
ED
, Davids
MS
, Kadia
TM
, et al. Consensus criteria for diagnosis, staging, and treatment response assessment of T-cell prolymphocytic leukemia
. Blood
. 2019
Oct
;134
(14
):1132
–43
.
[PubMed]
0006-497111.
Dearden
CE
, Matutes
E
, Cazin
B
, Tjønnfjord
GE
, Parreira
A
, Nomdedeu
B
, et al. High remission rate in T-cell prolymphocytic leukemia with CAMPATH-1H
. Blood
. 2001
Sep
;98
(6
):1721
–6
.
[PubMed]
0006-497112.
Keating
MJ
, Cazin
B
, Coutré
S
, Birhiray
R
, Kovacsovics
T
, Langer
W
, et al. Campath-1H treatment of T-cell prolymphocytic leukemia in patients for whom at least one prior chemotherapy regimen has failed
. J Clin Oncol
. 2002
Jan
;20
(1
):205
–13
.
[PubMed]
0732-183X13.
Dearden
CE
, Khot
A
, Else
M
, Hamblin
M
, Grand
E
, Roy
A
, et al. Alemtuzumab therapy in T-cell prolymphocytic leukemia: comparing efficacy in a series treated intravenously and a study piloting the subcutaneous route
. Blood
. 2011
Nov
;118
(22
):5799
–802
.
[PubMed]
0006-497114.
Sellner
L
, Brüggemann
M
, Schlitt
M
, Knecht
H
, Herrmann
D
, Reigl
T
, et al. GvL effects in T-prolymphocytic leukemia: evidence from MRD kinetics and TCR repertoire analyses
. Bone Marrow Transplant
. 2017
Apr
;52
(4
):544
–51
.
[PubMed]
0268-336915.
Guillaume
T
, Beguin
Y
, Tabrizi
R
, Nguyen
S
, Blaise
D
, Deconinck
E
, et al. Allogeneic hematopoietic stem cell transplantation for T-prolymphocytic leukemia: a report from the French society for stem cell transplantation (SFGM-TC)
. Eur J Haematol
. 2015
Mar
;94
(3
):265
–9
.
[PubMed]
0902-444116.
Wiktor-Jedrzejczak
W
, Dearden
C
, de Wreede
L
, van Biezen
A
, Brinch
L
, Leblond
V
, et al.; EBMT Chronic Leukemia Working Party
. Hematopoietic stem cell transplantation in T-prolymphocytic leukemia: a retrospective study from the European Group for Blood and Marrow Transplantation and the Royal Marsden Consortium
. Leukemia
. 2012
May
;26
(5
):972
–6
.
[PubMed]
0887-692417.
Jain
P
, Aoki
E
, Keating
M
, Wierda
WG
, O’Brien
S
, Gonzalez
GN
, et al. Characteristics, outcomes, prognostic factors and treatment of patients with T-cell prolymphocytic leukemia (T-PLL)
. Ann Oncol
. 2017
Jul
;28
(7
):1554
–9
.
[PubMed]
0923-753418.
Wiktor-Jedrzejczak
W
, Drozd-Sokolowska
J
, Eikema
DJ
, Hoek
J
, Potter
M
, Wulf
G
, et al. EBMT prospective observational study on allogeneic hematopoietic stem cell transplantation in T-prolymphocytic leukemia (T-PLL)
. Bone Marrow Transplant
. 2019
Sep
;54
(9
):1391
–8
.
[PubMed]
0268-336919.
Andersson
EI
, Pützer
S
, Yadav
B
, Dufva
O
, Khan
S
, He
L
, et al. Discovery of novel drug sensitivities in T-PLL by high-throughput ex vivo drug testing and mutation profiling
. Leukemia
. 2018
Mar
;32
(3
):774
–87
.
[PubMed]
0887-692420.
Schrader
A
, Crispatzu
G
, Oberbeck
S
, Mayer
P
, Pützer
S
, von Jan
J
, et al. Actionable perturbations of damage responses by TCL1/ATM and epigenetic lesions form the basis of T-PLL
. Nat Commun
. 2018
Feb
;9
(1
):697
.
[PubMed]
2041-172321.
Boidol
B
, Kornauth
C
, van der Kouwe
E
, Prutsch
N
, Kazianka
L
, Gültekin
S
, Hoermann
G
, Mayerhoefer
ME
, Hopfinger
G
, Hauswirth
A
, Panny
M
, Aretin
M-B
, Hilgarth
B
, Sperr
WR
, Valent
P
, Simonitsch-Klupp
I
, Moriggl
R
, Merkel
O
, Kenner
L
, Jäger
U
, Kubicek
S
, Staber
PB
: First in human response of BCL-2 inhibitor venetoclax in T-cell prolymphocytic leukemia. Blood 2017
:blood-2017-2005-785683.22.
Wei
M
, Koshy
N
, van Besien
K
, Inghirami
G
, Horwitz
SM
. Refractory T-Cell Prolymphocytic Leukemia with JAK3 Mutation: In Vitro and Clinical Synergy of Tofacitinib and Ruxolitinib
. Blood
. 2015
;126
(23
):5486
–5486
. 0006-497123.
Pu
JJ
, Poulose
J
, Zhu
J
, Malysz
J
, Fanburg-Smith
J
, Bayerl
M
. Ruxolitinib Maintenance Post Myelofibrosis Allogeneic Stem Cell Transplant
. Biol Blood Marrow Transplant
. 2019
;25
(3
):S123
. 1083-8791© 2020 S. Karger AG, Basel
2020
Copyright / Drug Dosage / Disclaimer
Copyright: All rights reserved. No part of this publication may be translated into other languages, reproduced or utilized in any form or by any means, electronic or mechanical, including photocopying, recording, microcopying, or by any information storage and retrieval system, without permission in writing from the publisher.
Drug Dosage: The authors and the publisher have exerted every effort to ensure that drug selection and dosage set forth in this text are in accord with current recommendations and practice at the time of publication. However, in view of ongoing research, changes in government regulations, and the constant flow of information relating to drug therapy and drug reactions, the reader is urged to check the package insert for each drug for any changes in indications and dosage and for added warnings and precautions. This is particularly important when the recommended agent is a new and/or infrequently employed drug.
Disclaimer: The statements, opinions and data contained in this publication are solely those of the individual authors and contributors and not of the publishers and the editor(s). The appearance of advertisements or/and product references in the publication is not a warranty, endorsement, or approval of the products or services advertised or of their effectiveness, quality or safety. The publisher and the editor(s) disclaim responsibility for any injury to persons or property resulting from any ideas, methods, instructions or products referred to in the content or advertisements.
You do not currently have access to this content.
