Idiopathic CD4+ lymphocytopenia (ICL) is the depletion of CD4+ lymphocytes to <300 cells/mm3 without human immunodeficiency virus infection or other causes of lymphocytopenia. ICL causes fatal infections; its etiology remains unclear and it lacks consensus regarding therapeutic options. We report the first patient with ICL who had a successful clinical course following a cord blood transplant (CBT). A 45-year-old woman was diagnosed with ICL and underwent partial hepatectomy for an abscess caused by the Mycobacterium avium complex. No specific gene alterations were detected through next generation sequencing-based evaluation. Following a reduced-intensity conditioning (RIC) regimen consisting of fludarabine, busulfan, and 4 Gy total body irradiation, a single-unit CBT was performed. Neutrophils were engrafted on day +14. CD4+ lymphocyte counts increased to over 300 cells/mm3 on day +436. After 75 months, she was alive without any sequelae. CBT with an RIC regimen could be a curable treatment option for ICL.

1.
Duncan
RA
,
von Reyn
CF
,
Alliegro
GM
,
Toossi
Z
,
Sugar
AM
,
Levitz
SM
.
Idiopathic CD4+ T-lymphocytopenia: four patients with opportunistic infections and no evidence of HIV infection
.
N Engl J Med
.
1993
;
328
(
6
):
393
8
. .
2.
Ahmad
DS
,
Esmadi
M
,
Steinmann
WC
.
Idiopathic CD4 lymphocytopenia: spectrum of opportunistic infections, malignancies, and autoimmune diseases
.
Avicenna J Med
.
2013
;
3
(
2
):
37
47
. .
3.
Régent
A
,
Autran
B
,
Carcelain
G
,
Cheynier
R
,
Terrier
B
,
Charmeteau-De Muylder
B
,
Idiopathic CD4 lymphocytopenia: clinical and immunologic characteristics and follow-up of 40 patients
.
Medicine (Baltimore)
.
2014
;
93
(
2
):
61
72
. .
4.
Smith
DK
,
Neal
JJ
,
Holmberg
SD
.
Unexplained opportunistic infections and CD4+ T-lymphocytopenia without HIV infection. An investigation of cases in the United States. The Centers for Disease Control Idiopathic CD4+ T-lymphocytopenia Task Force
.
N Engl J Med
.
1993
;
328
:
373
9
.
5.
Vijayakumar
S
,
Viswanathan
S
,
Aghoram
R
.
Idiopathic CD4 lymphocytopenia: current insights
.
Immunotargets Ther
.
2020
;
9
:
79
93
. .
6.
Yarmohammadi
H
,
Cunningham-Rundles
C
.
Idiopathic CD4 lymphocytopenia: pathogenesis, etiologies, clinical presentations and treatment strategies
.
Ann Allergy Asthma Immunol
.
2017
;
119
(
4
):
374
8
. .
7.
Zonios
DI
,
Falloon
J
,
Bennett
JE
,
Shaw
PA
,
Chaitt
D
,
Baseler
MW
,
Idiopathic CD4+ lymphocytopenia: natural history and prognostic factors
.
Blood
.
2008
;
112
(
2
):
287
94
. .
8.
Ho
DD
,
Cao
Y
,
Zhu
T
,
Farthing
C
,
Wang
N
,
Gu
G
,
Idiopathic CD4+ T-lymphocytopenia: immunodeficiency without evidence of HIV infection
.
N Engl J Med
.
1993
;
328
(
6
):
380
5
. .
9.
Bugault
F
,
Benati
D
,
Mouthon
L
,
Landires
I
,
Rohrlich
P
,
Pestre
V
,
Altered responses to homeostatic cytokines in patients with idiopathic CD4 lymphocytopenia
.
PLoS One
.
2013
;
8
(
1
):
e55570
. .
10.
Petersen
EJ
,
Rozenberg-Arska
M
,
Dekker
AW
,
Clevers
HC
,
Verdonck
LF
.
Allogeneic bone marrow transplantation can restore CD4+ T-lymphocyte count and immune function in idiopathic CD4+ T-lymphocytopenia
.
Bone Marrow Transplant
.
1996
;
18
(
4
):
813
5
.
11.
Routes
JM
,
Grossman
WJ
,
Verbsky
J
,
Laessig
RH
,
Hoffman
GL
,
Brokopp
CD
,
Statewide newborn screening for severe T-cell lymphopenia
.
JAMA
.
2009
;
302
(
22
):
2465
70
. .
12.
Cervera
C
,
Fernandez-Aviles
F
,
de la Calle-Martin
O
,
Bosch
X
,
Rovira
M
,
Plana
M
,
Non-myeloablative hematopoietic stem cell transplantation in the treatment of severe idiopathic CD4+ lymphocytopenia
.
Eur J Haematol
.
2011
;
87
(
1
):
87
91
. .
13.
Hamidieh
AA
,
Pourpak
Z
,
Hamdi
A
,
Nabavi
M
,
Ghavamzadeh
A
.
Successful fludarabine-based hematopoietic stem cell transplantation in a pediatric patient with idiopathic CD4+ lymphocytopenia
.
Pediatr Transplant
.
2013
;
17
(
4
):
E109
11
. .
14.
Morio
T
,
Atsuta
Y
,
Tomizawa
D
,
Nagamura-Inoue
T
,
Kato
K
,
Ariga
T
,
Outcome of unrelated umbilical cord blood transplantation in 88 patients with primary immunodeficiency in Japan
.
Br J Haematol
.
2011
;
154
(
3
):
363
72
. .
15.
Lum
SH
,
Bonney
D
,
Cheesman
E
,
Wrignt
NB
,
Hughes
S
,
Wynn
R
.
Successful curative therapy with rituximab and allogeneic haematopoietic stem cell transplantation for MALT lymphoma associated with STK4-mutated CD4+ lymphocytopenia
.
Pediatr Blood Cancer
.
2016
;
63
(
9
):
1657
9
. .
16.
Fujibayashi
T
,
Sugai
S
,
Miyasaka
N
,
Hayashi
Y
,
Tsubota
K
.
Revised Japanese criteria for Sjögren’s syndrome (1999): availability and validity
.
Mod Rheumatol
.
2004
;
14
:
425
34
.
17.
Kobayashi
Y
,
Matsui
H
,
Kanai
A
,
Tsumura
M
,
Okada
S
,
Miki
M
,
Identification of the integrin β3 L718P mutation in a pedigree with autosomal dominant thrombocytopenia with anisocytosis
.
Br J Haematol
.
2013
;
160
(
4
):
521
9
. .
18.
Chenhsu
RY
,
Loong
CC
,
Chou
MH
,
Lin
MF
,
Yang
WC
.
Renal allograft dysfunction associated with rifampin-tacrolimus interaction
.
Ann Pharmacother
.
2000
;
34
(
1
):
27
31
. .
19.
Mori
T
,
Aisa
Y
,
Kato
J
,
Nakamura
Y
,
Shimizu
T
,
Okamoto
S
.
Overcoming the effect of rifampin on the tacrolimus metabolism by itraconazole administration in an allogeneic hematopoietic stem cell transplant recipient
.
Int J Hematol
.
2010
;
91
(
3
):
553
4
. .
20.
Najima
Y
,
Sadato
D
,
Harada
Y
,
Oboki
K
,
Hirama
C
,
Toya
T
,
Prognostic impact of TP53 mutation, monosomal karyotype, and prior myeloid disorder in nonremission acute myeloid leukemia at allo-HSCT
.
Bone Marrow Transplant
.
2021
;
56
(
2
):
334
46
.
21.
Das
G
,
Vohra
H
,
Saha
B
,
Agrewala
JN
,
Mishra
GC
.
Apoptosis of Th1-like cells in experimental tuberculosis (TB)
.
Clin Exp Immunol
.
1999
;
115
(
2
):
324
8
. .
22.
Bignon
A
,
Régent
A
,
Klipfel
L
,
Desnoyer
A
,
de la Grange
P
,
Martinez
V
,
DUSP4-mediated accelerated T-cell senescence in idiopathic CD4 lymphopenia
.
Blood
.
2015
;
125
(
16
):
2507
18
. .
23.
Signorini
S
,
Pirovano
S
,
Fiorentini
S
,
Stellini
R
,
Bianchi
V
,
Albertini
A
,
Restriction of T-cell receptor repertoires in idiopathic CD4+ lymphocytopenia
.
Br J Haematol
.
2000
;
110
(
2
):
434
7
. .
24.
Hequet
O
,
Salles
G
,
Espinousse
D
,
Dumontet
C
,
Bouafia
F
,
Thieblemont
C
,
Multifocal progressive leukoencephalopathy occurring after refractory anemia and multiple infectious disorders consecutive to severe lymphopenia
.
Ann Hematol
.
2002
;
81
(
6
):
340
2
. .
25.
Chan
AY
,
Leiding
JW
,
Liu
X
,
Logan
BR
,
Burroughs
LM
,
Allenspach
EJ
,
Hematopoietic cell transplantation in patients with primary immune regulatory disorders (PIRD): a Primary Immune Deficiency Treatment Consortium (PIDTC) Survey
.
Front Immunol
.
2020
;
11
:
239
. .
26.
Gennery
AR
,
Albert
MH
,
Slatter
MA
,
Lankester
A
.
Hematopoietic stem cell transplantation for primary immunodeficiencies
.
Front Pediatr
.
2019
;
7
:
445
. .
27.
Rao
K
,
Amrolia
PJ
,
Jones
A
,
Cale
CM
,
Naik
P
,
King
D
,
Improved survival after unrelated donor bone marrow transplantation in children with primary immunodeficiency using a reduced-intensity conditioning regimen
.
Blood
.
2005
;
105
(
2
):
879
85
. .
28.
Barker
JN
,
Krepski
TP
,
DeFor
TE
,
Davies
SM
,
Wagner
JE
,
Weisdorf
DJ
.
Searching for unrelated donor hematopoietic stem cells: availability and speed of umbilical cord blood versus bone marrow
.
Biol Blood Marrow Transplant
.
2002
;
8
(
5
):
257
60
. .
29.
Konuma
T
,
Kanda
J
,
Inamoto
Y
,
Hayashi
H
,
Kobayashi
S
,
Uchida
N
,
Improvement of early mortality in single-unit cord blood transplantation for Japanese adults from 1998 to 2017
.
Am J Hematol
.
2020
;
95
(
4
):
343
53
.
30.
Nakasone
H
,
Fuji
S
,
Yakushijin
K
,
Onizuka
M
,
Shinohara
A
,
Ohashi
K
,
Impact of total body irradiation on successful neutrophil engraftment in unrelated bone marrow or cord blood transplantation
.
Am J Hematol
.
2017
;
92
(
2
):
171
8
. .
31.
Terakura
S
,
Kuwatsuka
Y
,
Yamasaki
S
,
Wake
A
,
Kanda
J
,
Inamoto
Y
,
GvHD prophylaxis after single-unit reduced intensity conditioning cord blood transplantation in adults with acute leukemia
.
Bone Marrow Transplant
.
2017
;
52
(
9
):
1261
7
. .
32.
Masouridi-Levrat
S
,
Simonetta
F
,
Chalandon
Y
.
Immunological basis of bone marrow failure after allogeneic hematopoietic stem cell transplantation
.
Front Immunol
.
2016
;
7
:
362
. .
33.
Cudkowicz
G
,
Bennett
M
.
Peculiar immunobiology of bone marrow allografts. I. Graft rejection by irradiated responder mice
.
J Exp Med
.
1971
;
134
(
1
):
83
102
. .
34.
Murphy
WJ
,
Kumar
V
,
Bennett
M
.
Acute rejection of murine bone marrow allografts by natural killer cells and T cells. Differences in kinetics and target antigens recognized
.
J Exp Med
.
1987
;
166
(
5
):
1499
509
. .
35.
Zonios
D
,
Sheikh
V
,
Sereti
I
.
Idiopathic CD4 lymphocytopenia: a case of missing, wandering or ineffective T cells
.
Arthritis Res Ther
.
2012
;
14
(
4
):
222
. .
36.
Sharrack
B
,
Saccardi
R
,
Alexander
T
,
Badoglio
M
,
Burman
J
,
Farge
D
,
Autologous haematopoietic stem cell transplantation and other cellular therapy in multiple sclerosis and immune-mediated neurological diseases: updated guidelines and recommendations from the EBMT Autoimmune Diseases Working Party (ADWP) and the Joint Accreditation Committee of EBMT and ISCT (JACIE)
.
Bone Marrow Transplant
.
2020
;
55
(
2
):
283
306
. .
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.