Leukemia & Lymphoma, 2014; Early Online: 1–6
© 2014 Informa UK, Ltd.
ISSN: 1042-8194 print / 1029-2403 online
DOI: 10.3109/10428194.2014.889827
Correspondence: Yujin Kobayashi, MD, PhD, Department of Hematology and Rheumatology, Nihon University School of Medicine, 30-1 Oyaguchi-Kamicho,
Itabashi-ku, Tokyo 173-8610, Japan. Tel: + 81-3-3972-8111, ext. 2402. Fax: + 81-3-3972-2893. E-mail: eumagene@gmail.com
Received 24 October 2013; revised 18 January 2014; accepted 25 January 2014
ORIGINAL ARTICLE: CLINICAL
Safety and efficacy of high-dose cyclophosphamide, etoposide and
ranimustine regimen followed by autologous peripheral blood stem cell
transplant for patients with diffuse large B-cell lymphoma
Yujin Kobayashi
1
, Yoshihiro Hatta
1
, Masahiko Sugitani
2
, Atsuko Hojo
1
, Masaru Nakagawa
1
, Machiko Kusuda
1
,
Yoshihito Uchino
1
, Hiromichi Takahashi
1
, Satomi Kiso
1
, Yukio Hirabayashi
1
, Mai Yagi
1
, Hitomi Kodaira
1
,
Daisuke Kurita
1
, Katsuhiro Miura
1
, Noriyoshi Iriyama
1
, Sumiko Kobayashi
1
, Yoshimasa Kura
3
, Akira Horikoshi
1
,
Umihiko Sawada
3
, Jin Takeuchi
1
& Masami Takei
1
1
Department of Hematology and Rheumatology and
2
Department of Pathology, Nihon University School of Medicine, Tokyo,
Japan and
3
Department of Hematology and Oncology, Kasukabe Municipal Hospital, Saitama, Japan
Introduction
Relapsed or refractory difuse large B-cell lymphoma
(DLBCL) can be a candidate for high-dose chemotherapy
(HDT) followed by autologous peripheral blood stem cell
transplant (PBSCT) in patients with chemotherapy-sensitive
disease [1,2]. he eicacy of upfront PBSCT for high-risk
DLBCL has also been reported in terms of progression-free
survival (PFS) [3]. Although several regimens containing
the nitrosourea carmustine (BCNU), such as carmustine,
etoposide, cytarabine and melphalan (BEAM) and cyclo-
phosphamide, carmustine and etoposide (CBV), have
been widely used for HDT in lymphoma, an optimal condi-
tioning regimen in terms of toxicity and eicacy has not been
determined [4].
We designed a new conditioning regimen using high-
dose cyclophosphamide, etoposide and ranimustine
(MCNU; CEM regimen) for autologous PBSCT. We report
the safety and eicacy of the CEM regimen for relapsed or
high-risk DLBCL or DLBCL associated with follicular
lymphoma (FL/DLBCL).
Patients and methods
Patients
Patients who underwent autologous PBSCT following
the CEM regimen between March 1999 and June 2011
at Nihon University Itabashi Hospital for the treatment
of relapsed or high-risk, histologically proven de novo
DLBCL or FL/DLBCL were identiied from our trans-
plant database. heir demographic and transplant data
records were collected by chart review. High-risk DLBCL
was deined as partial response (PR) or no response to
initial treatment, or high-intermediate/high risk disease
according to the international prognostic index (IPI) at
initial diagnosis [5]. Age-adjusted IPI was used for patients
under 60 years. Clinical staging was performed by com-
puted tomography scanning of the neck, thorax, abdomen
and pelvis, bone marrow (BM) biopsy, gallium scanning
or positron emission tomography, cerebrospinal luid
examination and other tools such as magnetic resonance
imaging if indicated.
Abstract
We retrospectively evaluated the safety and eicacy of high-
dose chemotherapy consisting of cyclophosphamide, etoposide
and ranimustine (CEM) with autologous peripheral blood stem
cell transplant (PBSCT) in 55 adult patients with relapsed or
high-risk de novo difuse large B-cell lymphoma (DLBCL) or
DLBCL associated with follicular lymphoma. This included 36
patients in the upfront setting in their irst complete remission.
The median follow-up of 42 patients surviving at the time of
the analysis was 52 months (range 1–159). Relapse or disease
progression after PBSCT was a frequent cause of death, but no
therapy-related mortality associated with PBSCT was observed.
The 5-year overall survival and progression-free survival were
70.6% (95% conidence interval [CI], 54.0–82.1) and 57.0% (95%
CI, 39.5–71.2), respectively. Chronic renal impairment, therapy-
related myelodysplastic syndrome and prostate cancer were
the major late complications. The CEM regimen is a tolerable,
efective conditioning regimen for autologous PBSCT for DLBCL,
with no therapy-related mortality observed.
Keywords: Difuse large B-cell lymphoma, follicular lymphoma,
autologous peripheral blood stem cell transplant, CEM
regimen, high-dose chemotherapy, conditioning
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