• The survival benefit of allo-HCT was investigated in 1114 CMML patients with time-dependent analyses and multistate models.

  • Performing allo-HCT before transformation decreases life expectancy in lower-risk patients but may be considered in higher-risk patients.

To determine the survival benefit of allogeneic hematopoietic cell transplantation (allo-HCT) in chronic myelomonocytic leukemias (CMML), we assembled a retrospective cohort of CMML patients 18-70 years old diagnosed between 2000 and 2014 from an international CMML dataset (n = 730) and the EBMT registry (n = 384). The prognostic impact of allo-HCT was analyzed through univariable and multivariable time-dependent models and with a multistate model, accounting for age, sex, CMML prognostic scoring system (low or intermediate-1 grouped as lower-risk, intermediate-2 or high as higher-risk) at diagnosis, and AML transformation. In univariable analysis, lower-risk CMMLs had a 5-year overall survival (OS) of 20% with allo-HCT vs 42% without allo-HCT (P < .001). In higher-risk patients, 5-year OS was 27% with allo-HCT vs 15% without allo-HCT (P = .13). With multistate models, performing allo-HCT before AML transformation reduced OS in patients with lower-risk CMML, and a survival benefit was predicted for men with higher-risk CMML. In a multivariable analysis of lower-risk patients, performing allo-HCT before transformation to AML significantly increased the risk of death within 2 years of transplantation (hazard ratio [HR], 3.19; P < .001), with no significant change in long-term survival beyond this time point (HR, 0.98; P = .92). In higher-risk patients, allo-HCT significantly increased the risk of death in the first 2 years after transplant (HR 1.46; P = .01) but not beyond (HR, 0.60; P = .09). Performing allo-HCT before AML transformation decreases life expectancy in lower-risk patients but may be considered in higher-risk patients.

1.
Srour
SA
,
Devesa
SS
,
Morton
LM
, et al
.
Incidence and patient survival of myeloproliferative neoplasms and myelodysplastic/myeloproliferative neoplasms in the United States, 2001-12
.
Br J Haematol.
2016
;
174
(
3
):
382
-
396
.
2.
Itzykson
R
,
Kosmider
O
,
Renneville
A
, et al
.
Prognostic score including gene mutations in chronic myelomonocytic leukemia
.
J Clin Oncol.
2013
;
31
(
19
):
2428
-
2436
.
3.
Elena
C
,
Gallì
A
,
Such
E
, et al
.
Integrating clinical features and genetic lesions in the risk assessment of patients with chronic myelomonocytic leukemia
.
Blood.
2016
;
128
(
10
):
1408
-
1417
.
4.
Patnaik
MM
,
Padron
E
,
LaBorde
RR
, et al
.
Mayo prognostic model for WHO-defined chronic myelomonocytic leukemia: ASXL1 and spliceosome component mutations and outcomes
[published correction appears in Leukemia. 2013;27(10):2112].
Leukemia.
2013
;
27
(
7
):
1504
-
1510
.
5.
Padron
E
,
Garcia-Manero
G
,
Patnaik
MM
, et al
.
An international data set for CMML validates prognostic scoring systems and demonstrates a need for novel prognostication strategies
.
Blood Cancer J.
2015
;
5
(
7
):
e333
.
6.
Kerbauy
DMB
,
Chyou
F
,
Gooley
T
, et al
.
Allogeneic hematopoietic cell transplantation for chronic myelomonocytic leukemia
.
Biol Blood Marrow Transplant.
2005
;
11
(
9
):
713
-
720
.
7.
Eissa
H
,
Gooley
TA
,
Sorror
ML
, et al
.
Allogeneic hematopoietic cell transplantation for chronic myelomonocytic leukemia: relapse-free survival is determined by karyotype and comorbidities
.
Biol Blood Marrow Transplant.
2011
;
17
(
6
):
908
-
915
.
8.
Park
S
,
Labopin
M
,
Yakoub-Agha
I
, et al
.
Allogeneic stem cell transplantation for chronic myelomonocytic leukemia: a report from the Societe Francaise de Greffe de Moelle et de Therapie Cellulaire
.
Eur J Haematol.
2013
;
90
(
5
):
355
-
364
.
9.
Symeonidis
A
,
van Biezen
A
,
de Wreede
L
, et al;
Chronic Malignancies Working Party of the European Group for Blood and Marrow Transplantation
.
Achievement of complete remission predicts outcome of allogeneic haematopoietic stem cell transplantation in patients with chronic myelomonocytic leukaemia. A study of the Chronic Malignancies Working Party of the European Group for Blood and Marrow Transplantation
.
Br J Haematol.
2015
;
171
(
2
):
239
-
246
.
10.
Kongtim
P
,
Popat
U
,
Jimenez
A
, et al
.
Treatment with hypomethylating agents before allogeneic stem cell transplant improves progression-free survival for patients with chronic myelomonocytic leukemia
.
Biol Blood Marrow Transplant.
2016
;
22
(
1
):
47
-
53
.
11.
Itonaga
H
,
Aoki
K
,
Aoki
J
, et al
.
Prognostic impact of donor source on allogeneic hematopoietic stem cell transplantation outcomes in adults with chronic myelomonocytic leukemia: a nationwide retrospective analysis in Japan
.
Biol Blood Marrow Transplant.
2018
;
24
(
4
):
840
-
848
.
12.
Woo
J
,
Choi
DR
,
Storer
BE
, et al
.
Impact of clinical, cytogenetic, and molecular profiles on long-term survival after transplantation in patients with chronic myelomonocytic leukemia
.
Haematologica.
2020
;
105
(
3
):
652
-
660
.
13.
Cutler
CS
,
Lee
SJ
,
Greenberg
P
, et al
.
A decision analysis of allogeneic bone marrow transplantation for the myelodysplastic syndromes: delayed transplantation for low-risk myelodysplasia is associated with improved outcome
.
Blood.
2004
;
104
(
2
):
579
-
585
.
14.
Koreth
J
,
Pidala
J
,
Perez
WS
, et al
.
Role of reduced-intensity conditioning allogeneic hematopoietic stem-cell transplantation in older patients with de novo myelodysplastic syndromes: an international collaborative decision analysis
.
J Clin Oncol.
2013
;
31
(
21
):
2662
-
2670
.
15.
Kröger
N
,
Sockel
K
,
Wolschke
C
, et al
.
Comparison between 5-azacytidine treatment and allogeneic stem-cell transplantation in elderly patients with advanced MDS according to donor availability (VidazaAllo Study)
.
J Clin Oncol.
2021
;
39
(
30
):
3318
-
3327
.
16.
Nakamura
R
,
Saber
W
,
Martens
MJ
, et al
.
Biologic assignment trial of reduced-intensity hematopoietic cell transplantation based on donor availability in patients 50-75 years of age with advanced myelodysplastic syndrome
.
J Clin Oncol.
2021
;
39
(
30
):
3328
-
3339
.
17.
Robin
M
,
Porcher
R
,
Adès
L
, et al
.
HLA-matched allogeneic stem cell transplantation improves outcome of higher risk myelodysplastic syndrome a prospective study on behalf of SFGM-TC and GFM
.
Leukemia.
2015
;
29
(
7
):
1496
-
1501
.
18.
Itzykson
R
,
Santini
V
,
Chaffaut
C
, et al
.
Decitabine versus hydroxyurea for advanced proliferative CMML: results of the Emsco Randomized Phase 3 Dacota Trial
.
Blood.
2020
;
136
(
Supplement 1
):
53
-
54
.
19.
Pleyer
L
,
Leisch
M
,
Kourakli
A
, et al
.
Outcomes of patients with chronic myelomonocytic leukaemia treated with non-curative therapies: a retrospective cohort study
.
Lancet Haematol.
2021
;
8
(
2
):
e135
-
e148
.
20.
Patnaik
MM
,
Wassie
EA
,
Padron
E
, et al
.
Chronic myelomonocytic leukemia in younger patients: molecular and cytogenetic predictors of survival and treatment outcome
[published correction appears in Blood Cancer J. 2015;5(1):e270].
Blood Cancer J.
2015
;
5
(
2
):
e280
.
21.
Vardiman
JW
,
Thiele
J
,
Arber
DA
, et al
.
The 2008 revision of the World Health Organization (WHO) classification of myeloid neoplasms and acute leukemia: rationale and important changes
.
Blood.
2009
;
114
(
5
):
937
-
951
.
22.
Such
E
,
Germing
U
,
Malcovati
L
, et al
.
Development and validation of a prognostic scoring system for patients with chronic myelomonocytic leukemia
.
Blood.
2013
;
121
(
15
):
3005
-
3015
.
23.
Such
E
,
Cervera
J
,
Costa
D
, et al
.
Cytogenetic risk stratification in chronic myelomonocytic leukemia
.
Haematologica.
2011
;
96
(
3
):
375
-
383
.
24.
Saraceni
F
,
Labopin
M
,
Gorin
NC
, et al;
Acute Leukemia Working Party (ALWP) of the European society for Blood and Marrow Transplantation (EBMT)
.
Matched and mismatched unrelated donor compared to autologous stem cell transplantation for acute myeloid leukemia in first complete remission: a retrospective, propensity score-weighted analysis from the ALWP of the EBMT
.
J Hematol Oncol.
2016
;
9
(
1
):
79
.
25.
Bacigalupo
A
,
Ballen
K
,
Rizzo
D
, et al
.
Defining the intensity of conditioning regimens: working definitions
.
Biol Blood Marrow Transplant.
2009
;
15
(
12
):
1628
-
1633
.
26.
de Wreede
LC
,
Fiocco
M
,
Putter
H
.
The mstate package for estimation and prediction in non- and semi-parametric multi-state and competing risks models
.
Comput Methods Programs Biomed.
2010
;
99
(
3
):
261
-
274
.
27.
de Wreede
LC
,
Fiocco
M
,
Putter
H
.
mstate: an R package for the analysis of competing risks and multi-state models
.
J Stat Softw.
2011
;
38
(
7
):
1
-
30
.
28.
Logan
BR
.
Review of multistate models in hematopoietic cell transplantation studies
.
Biol Blood Marrow Transplant.
2013
;
19
(
1 Suppl
):
S84
-
S87
.
29.
van Houwelingen
H
,
Putter
H
.
Dynamic Prediction in Clinical Survival Analysis.
1st ed.
Boca Raton, Florida
:
CRC Press
;
2012
.
30.
Shuster
JJ
.
Median follow-up in clinical trials
.
J Clin Oncol.
1991
;
9
(
1
):
191
-
192
.
31.
Simon
R
,
Makuch
RW
.
A non-parametric graphical representation of the relationship between survival and the occurrence of an event: application to responder versus non-responder bias
.
Stat Med.
1984
;
3
(
1
):
35
-
44
.
32.
Mantel
N
,
Byar
DP
.
Evaluation of response-time data involving transient states: an illustration using heart-transplant data
.
J Am Stat Assoc.
1974
;
69
(
345
):
81
-
86
.
33.
Gagelmann
N
,
Bogdanov
R
,
Stolzel
F
, et al
.
Long-term survival benefit after allogeneic hematopoietic cell transplantation for chronic myelomonocytic leukemia
Transplant Cell Ther. 
2021
;
27
(
1
):
95.e1
-
95.e4
.
34.
Pophali
P
,
Matin
A
,
Mangaonkar
AA
, et al
.
Prognostic impact and timing considerations for allogeneic hematopoietic stem cell transplantation in chronic myelomonocytic leukemia
.
Blood Cancer J.
2020
;
10
(
11
):
121
.
35.
Eefting
M
,
de Wreede
LC
,
Halkes
CJ
, et al
.
Multi-state analysis illustrates treatment success after stem cell transplantation for acute myeloid leukemia followed by donor lymphocyte infusion
.
Haematologica.
2016
;
101
(
4
):
506
-
514
.
36.
Alessandrino
EP
,
Porta
MG
,
Malcovati
L
, et al;
Gruppo Italiano Trapianto di Midollo Osseo (GITMO)
.
Optimal timing of allogeneic hematopoietic stem cell transplantation in patients with myelodysplastic syndrome
.
Am J Hematol.
2013
;
88
(
7
):
581
-
588
.
37.
Della Porta
MG
,
Jackson
CH
,
Alessandrino
EP
, et al
.
Decision analysis of allogeneic hematopoietic stem cell transplantation for patients with myelodysplastic syndrome stratified according to the revised International Prognostic Scoring System
.
Leukemia.
2017
;
31
(
11
):
2449
-
2457
.
38.
Brand
R
,
Putter
H
,
van Biezen
A
, et al
.
Comparison of allogeneic stem cell transplantation and non-transplant approaches in elderly patients with advanced myelodysplastic syndrome: optimal statistical approaches and a critical appraisal of clinical results using non-randomized data
.
PLoS One.
2013
;
8
(
10
):
e74368
.
39.
Patnaik
MM
,
Pierola
AA
,
Vallapureddy
R
, et al
.
Blast phase chronic myelomonocytic leukemia: Mayo-MDACC collaborative study of 171 cases
.
Leukemia.
2018
;
32
(
11
):
2512
-
2518
.
40.
Ruggiu
M
,
Cassinat
B
,
Kiladjian
JJ
, et al
.
Should transplantation still be considered for Ph1-negative myeloproliferative neoplasms in transformation?
Biol Blood Marrow Transplant.
2020
;
26
(
6
):
1160
-
1170
.
41.
Kröger
N
,
Eikema
DJ
,
Köster
L
, et al;
Chronic Malignancies Working Party of the European Society for Blood Marrow Transplantation
.
Impact of primary disease on outcome after allogeneic stem cell transplantation for transformed secondary acute leukaemia
.
Br J Haematol.
2019
;
185
(
4
):
725
-
732
.
42.
Aul
C
,
Gattermann
N
,
Heyll
A
,
Germing
U
,
Derigs
G
,
Schneider
W
.
Primary myelodysplastic syndromes: analysis of prognostic factors in 235 patients and proposals for an improved scoring system
.
Leukemia.
1992
;
6
(
1
):
52
-
59
.
43.
Greenberg
P
,
Cox
C
,
LeBeau
MM
, et al
.
International scoring system for evaluating prognosis in myelodysplastic syndromes
.
Blood.
1997
;
89
(
6
):
2079
-
2088
.
44.
Onida
F
,
Kantarjian
HM
,
Smith
TL
, et al
.
Prognostic factors and scoring systems in chronic myelomonocytic leukemia: a retrospective analysis of 213 patients
.
Blood.
2002
;
99
(
3
):
840
-
849
.
45.
Kantarjian
H
,
O’Brien
S
,
Ravandi
F
, et al
.
Proposal for a new risk model in myelodysplastic syndrome that accounts for events not considered in the original International Prognostic Scoring System
.
Cancer.
2008
;
113
(
6
):
1351
-
1361
.
46.
Greenberg
PL
,
Tuechler
H
,
Schanz
J
, et al
.
Revised international prognostic scoring system for myelodysplastic syndromes
.
Blood.
2012
;
120
(
12
):
2454
-
2465
.
47.
Yoshizato
T
,
Nannya
Y
,
Atsuta
Y
, et al
.
Genetic abnormalities in myelodysplasia and secondary acute myeloid leukemia: impact on outcome of stem cell transplantation
.
Blood.
2017
;
129
(
17
):
2347
-
2358
.
48.
Carré
M
,
Porcher
R
,
Finke
J
, et al
.
Role of age and hematopoietic cell transplantation-specific comorbidity index in myelodysplastic patients undergoing an allotransplant: a retrospective study from the Chronic Malignancies Working Party of the European Group for Blood and Marrow Transplantation
.
Biol Blood Marrow Transplant.
2020
;
26
(
3
):
451
-
457
.
49.
Gagelmann
N
,
Badbaran
A
,
Beelen
DW
, et al
.
A prognostic score including mutation profile and clinical features for patients with CMML undergoing stem cell transplantation
.
Blood Adv.
2021
;
5
(
6
):
1760
-
1769
.
50.
Togami
K
,
Chung
SS
,
Madan
V
, et al
.
Sex-biased ZRSR2 mutations in myeloid malignancies impair plasmacytoid dendritic cell activation and apoptosis
.
Cancer Discov.
2022
;
12
(
2
):
522
-
541
.
51.
DeZern
AE
,
Zeidan
AM
,
Barnard
J
, et al;
Evans MDS Clinical Research Consortium
.
Differential response to hypomethylating agents based on sex: a report on behalf of the MDS Clinical Research Consortium (MDS CRC)
.
Leuk Lymphoma.
2017
;
58
(
6
):
1325
-
1331
.
52.
Yahng
SA
,
Jeon
YW
,
Yoon
JH
, et al
.
Dynamic prognostic value of the revised international prognostic scoring system following pretransplant hypomethylating treatment in myelodysplastic syndrome
.
Bone Marrow Transplant.
2017
;
52
(
4
):
522
-
531
.
53.
Malcovati
L
,
Germing
U
,
Kuendgen
A
, et al
.
Time-dependent prognostic scoring system for predicting survival and leukemic evolution in myelodysplastic syndromes
.
J Clin Oncol.
2007
;
25
(
23
):
3503
-
3510
.
54.
Platzbecker
U
,
Schetelig
J
,
Finke
J
, et al;
Groupe Francophone des Myelodysplasies
.
Allogeneic hematopoietic cell transplantation in patients age 60-70 years with de novo high-risk myelodysplastic syndrome or secondary acute myelogenous leukemia: comparison with patients lacking donors who received azacitidine
.
Biol Blood Marrow Transplant.
2012
;
18
(
9
):
1415
-
1421
.
55.
Zeiser
R
,
von Bubnoff
N
,
Butler
J
, et al;
REACH2 Trial Group
.
Ruxolitinib for glucocorticoid-refractory acute graft-versus-host disease
.
N Engl J Med.
2020
;
382
(
19
):
1800
-
1810
.
56.
Marty
FM
,
Ljungman
P
,
Chemaly
RF
, et al
.
Letermovir prophylaxis for cytomegalovirus in hematopoietic-cell transplantation
.
N Engl J Med.
2017
;
377
(
25
):
2433
-
2444
.
57.
Holtan
SG
,
DeFor
TE
,
Lazaryan
A
, et al
.
Composite end point of graft-versus-host disease-free, relapse-free survival after allogeneic hematopoietic cell transplantation
.
Blood.
2015
;
125
(
8
):
1333
-
1338
.
58.
Itzykson
R
,
Fenaux
P
,
Bowen
D
, et al
.
Diagnosis and treatment of chronic myelomonocytic leukemias in adults: recommendations from the European Hematology Association and the European LeukemiaNet
.
HemaSphere.
2018
;
2
(
6
):
e150
.
You do not currently have access to this content.

Sign in via your Institution