LETTER TO THE EDITOR
A retrospective comparison of conventional intensity conditioning and
reduced-intensity conditioning for allogeneic hematopoietic cell
transplantation in myelofibrosis
Bone Marrow Transplantation (2009) 44, 317–320;
doi:10.1038/bmt.2009.10; published online 23 February 2009
Allogeneic hematopoietic cell transplantation (alloHCT) is
the only curative treatment modality for patients with
myelofibrosis (MF). Earlier studies using myeloablative
regimens have shown that approximately 35–45% of
patients achieve long-term cure from MF.1–3 The curative
potential of alloHCT is related to a combination of the
reduction or eradication of the malignant clone by the
conditioning regimen and a graft-versus-MF effect. A
major barrier to alloHCT using conventional intensity
conditioning (CIC) regimens is the high TRM observed in
30–45% of patients, which restricts the use of the procedure
to a limited number of young and fit patients. In the last
decade, several studies have demonstrated the feasibility of
non-myeloablative or reduced-intensity transplantation,
collectively called reduced-intensity conditioning (RIC)
regimens, in the management of MF.4–7 However, com-
parative data on the outcomes of CIC regimens to RIC
regimens in patients with MF are scanty.7 Owing to the low
transplant activity for MF, it is difficult to conduct such
studies. Even the large centers do only a few of these
transplants every year. The majority of patients with MF
are in the older age group and physicians may be hesitant
to refer these patients to the transplant centers. It is not
known whether patients undergoing RIC have a similar
benefit from the transplant procedure as patients under-
going CIC. There is a concern that resolution of fibrosis
may not be complete and there may be an increased risk of
relapse in patients with MF with RIC when compared with
CIC as seen in some of the hematological malignancies.
We analyzed the impact of conditioning intensity on
the outcomes of alloHCT in MF. This multicenter retro-
spective study included 46 consecutive patients treated at
three Canadian and four European transplant centers
between January 1998 and December 2005. The diagnosis
of MF was made on the basis of criteria published by
Barosi et al.8 Data on surviving patients were updated as of
October 2007. This report includes 11 patients reported in
earlier studies with extended follow-up.6,7 The indication
for alloHCT was intermediate- or high-risk disease
(according to the Dupriez Score) in 39 (85%) patients,
whereas seven patients underwent transplant for low-risk
disease because of constitutional symptoms (n¼ 5) or
recurrent thrombosis (n¼ 2). Twenty-three patients re-
ceived CIC and 23 received RIC. Of the 23 patients
receiving CIC regimens, 22 received high-dose CY
(120mg/m2) in combination with fractionated TBI (1000–
1200 cGY). One patient received CY 120mg/m2 with BU
(p.o. 16mg/kg). Of the 23 patients receiving RIC, 17
patients received fludarabine (120–180mg/m2) in combina-
tion with 8–10mg/kg p.o. BU (n¼ 14), 6.4mg/kg i.v.
BU (n¼ 2) or 140mg/m2 melphalan (n¼ 1). Six patients
received minimal conditioning with fludarabine (90mg/m2)
and low-dose TBI (200 cGY). GVHD prophylaxis in the
two cohorts is summarized in Table 1. A significantly
higher proportion of patient in the RIC cohort received
serotherapy with anti-thymocyte globulin or alemtuzumab.
Engraftment, graft failure, severity of acute and chronic
GVHD were defined according to previously published
standard criteria.9 PFS and overall survival were calculated
from the transplant date by using the Kaplan–Meier
method. The cumulative incidences were estimated for
graft failure (primary and secondary), acute GVHD and
chronic GVHD, whereas death from any cause was treated
as a competing risk.
Baseline characteristics and transplant-related outcomes
of the patients undergoing CIC and RIC are summarized in
Tables 1 and 2, respectively. No significant differences were
found in the cumulative incidences of graft failure in the
two study cohorts. Patients in whom the results of pre-
BMT and a minimum of two post-BMT biopsies were
available were considered evaluable for the assessment of
regression of fibrosis. These data were available on 24
patients (CIC cohort, 14 (61%); RIC cohort, 10 (43%)) and
no significant differences were observed in time to
resolution of fibrosis. The groups did not differ in the
cumulative incidence of relapse/progression. At a median
follow-up of 50 (20–89) months for survivors, there was a
trend toward better PFS or overall survival of patients
transplanted with RIC regimens (Table 2).
The results of this study suggest that both types of
conditioning regimens have curative potential in patients
with MF. Patients receiving RIC were significantly older
and tended to have longer disease duration and poorer
performance status. In spite of these differences, a similar
survival was observed for both study cohorts. One of the
concerns using an RIC approach is the higher rate of
disease relapse. This study did not reveal any significant
difference in relapse/progression among recipients of CIC
or RIC. An earlier study from the myeloproliferative
disease research consortium using the RIC approach
reported a relapse rate of 14% in 21 patients with MF.4
Another multicenter study from Germany did not observe
any cases of relapse in 21 patients with MF treated with
RIC.6 Similar data were obtained in a recent Swedish study
Bone Marrow Transplantation (2009) 44, 317–320
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Table 1 Baseline patient, donor, disease and transplant-related characteristics
Characteristics CIC (%) N¼ 23 RIC (%) N¼ 23 P-value
Median age at BMT (years) (range) 47 (31–60) 54 (38–74) 0.003
Age at BMT 0.003
o50 years 16 (70) 6 (26)
X50 years 7 (30) 17 (74)
Proportion of male patients 18 (78) 16 (70) 0.50
PS at BMT 0.09
o80 2 (9) 3 (13)
X80 21 (91) 16 (70)
Missing 0 4 (17)
Myelofibrosis 0.52
Primary 15 (65) 17 (74)
Secondary 8 (35) 6 (26)
PTMF 8 5
PPMF 0 1
Dupriez score 0.35
Low (0) 02 (9) 5 (22)
Intermediate (1) 14 (61) 14 (61)
High (2) 7 (30) 04 (17)
Spleen at BMT 0.42
Splenectomy 2 (9) 3 (13)
Not palpable 2 (9) 5 (22)
Enlarged 18 (82) 15 (65)
Time Dx. to BMT 0.05
o1 year 16 (70) 8 (35)
1–3 years 5 (21) 8 (35)
43 years 2 (9) 7 (30)
Source of stem cells 0.0002
BM 14 (61) 2 (9)
PB 9 (39) 21 (91)
Donor 0.77
MSD/MFD 13 (56) 12 (52)
AD 10 (44) 11 (48)
MMFD/MUD/MMUD 2/7/1 0/11/0
CMV status (R/D)
Pos/pos or neg 11 (48) 11 (48) 1.0
Neg/pos 5 (22) 5 (22)
Neg/neg 7 (30) 7 (30)
ABO mismatch 0.55
No 15 (65) 13 (57)
Yes 8 (35) 10 (43)
Major/minor/bidirectional 3/5/0 3/6/1
Conditioning regimens —
CY+TBI 22 (96) —
Bu+CY 1 (4) —
Flu+Bu — 16 (70)
Flu+Me — 1 (4)
Flu+TBI 200 — 6 (26)
GVHD prophylaxis 0.01
CsA+MTX 21 (91) 12 (52)
CsA+MMF 1 (4) 8 (36)
CsA alone 1 (4) 3 (13)
Serotherapy 0.001
No 22 (96) 7 (30)
Yes 1 (4) 16 (70)
ATG/alemtuzumab 1/0 14/2
Abbreviations: AD¼ alternative donor; ATG¼ anti-thymocyte globulin; CIC¼ conventional intensity conditioning; D¼ donor; Dx¼ diagnosis;
Flu¼ fludarabine; Mel¼melphalan; MFD¼matched family donor; MMF¼mycophenolate mofetil; MMFD¼mismatched family donor;
MMUD¼mismatched unrelated donor; MSD¼matched sibling donor; MUD¼matched unrelated donor; PPMF¼post-polycythemic myelofibrosis;
PS¼ performance status; PTMF¼post-thrombocythemic myelofibrosis; R¼ recipient; RIC¼ reduced-intensity conditioning.
Letter to the Editor
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Bone Marrow Transplantation