International Journal of Myeloma 8(3): 11–15, 2018
©Japanese Society of Myeloma

CASE REPORT

Successful autologous peripheral blood stem cell harvest and­transplantation after splenectomy in a patient with multiple­myeloma with hereditary spherocytosis
Daisuke FURUYA1,4, Rikio SUZUKI1,4, Jun AMAKI1, Daisuke OGIYA1, Hiromichi MURAYAMA1,2,­Hidetsugu KAWAI1, Akifumi ICHIKI1,3, Sawako SHIRAIWA1, Shohei KAWAKAMI1, Kaito HARADA1,
Yoshiaki OGAWA1, Hiroshi KAWADA1 and Kiyoshi ANDO1
Hereditary spherocytosis (HS) is the most common inherited red cell membrane disorder worldwide. We herein
report a 58-year-old male HS patient with mild splenomegaly who developed symptomatic multiple myeloma (MM).
Autologous stem cell transplantation (ASCT) was considered to be adopted against MM, although there was a
possibility of splenic rupture following stem cell mobilization. Therefore, splenectomy was performed prior to stem
cell harvest, and he was able to safely mobilize sufficient CD34+ cells with G-CSF and plerixafor and undergo ASCT.
This case suggests that stem cell mobilization after splenectomy is safe and effective in HS patients complicatedwith malignancies.
Key words: multiple myeloma, hereditary spherocytosis, splenectomy, autologous peripheral blood stem cell harvest

Introduction

Consolidation with melphalan-based HDT followed by ASCT
is still the standard treatment option for transplant-eligible

Multiple myeloma (MM) is characterized by clonal prolifera-

patients with MM, leading to higher complete response rates

tion of abnormal plasma cells in the bone marrow (BM) micro-

and increased progression-free survival and overall survival

environment, monoclonal protein in the blood and/or urine,

compared with conventional chemotherapy regimens [2].

bone lesions, and immunodeficiency [1]. In recent years, theImportantly, the emergence of novel agent-based therapy

introduction of high-dose chemotherapy (HDT) and autol­

combined with ASCT has revolutionized MM therapy [2].

ogous stem cell transplantation (ASCT) and novel therapies­Mobilized peripheral blood (PB) is the most common source

including bortezomib (BTZ), thalidomide, and lenalidomideof hematopoietic stem cells (HSCs) for ASCT. Recombinant

have prolonged survival of patients with MM [1]. However,

granulocyte colony stimulating factor (G-CSF) is the most

relapses are common, and further novel therapies arecommon representative mobilization agent and is adminis­

needed.

tered either alone or in conjunction with chemotherapy [3].
On the other hand, control of complications induced by G-­
CSF is an important issue. Tigue et al. reported that G-CSF-

Received: June 17, 2018, accepted: September 14, 2018
1
Department of Hematology/Oncology, Tokai University School of
Medicine, Isehara, Kanagawa, Japan2
Department of Hematology, Ebina General Hospital, Ebina,
Kanagawa, Japan3
Department of Hematology, Ozawa Hospital, Odawara, Kanagawa,Japan
4
These authors contributed equally to this work
Corresponding author: Kiyoshi ANDO
Department of Hematology/Oncology, Tokai University School of
Medicine, 143 Shimokasuya, Isehara, Kanagawa, Japan
E-mail: andok@keyaki.cc.u-tokai.ac.jp

associated adverse events include bone pain, splenic rupture,allergic reactions, flares of underlying autoimmune disorders,lung injury, and vascular events [4]. Among them, splenic
rupture can be a s­erious and sometimes life-threatening
complication [4].
Hereditary spherocytosis (HS) is a group of inherited red cell
membrane disorders that is heterogeneous regarding clinicalseverity, protein defects, and mode of inheritance [5]. The typical clinical features are hemolysis with anemia, jaundice, reticulocytosis, gallstones, splenomegaly, and spherocytes on a PB
smear [6]. The prevalence of palpable splenomegaly varies
from about 50% in young children to 75–95% in older children

International Journal of Myeloma

vol. 8 no. 3 (2018)11

FURUYA et al.

and adults. Typically, the spleen is moderately enlarged, but ittion tests (aspartate aminotransferase 866 U/L, alanine amino-

can be massive, because the spleen is the site of sequestrationtransferase 496 U/L, total bilirubin 6.3 mg/dl, direct bilirubin

and phagocytosis of undeformable HS red blood cells [6].

3.1 mg/dL, NH3 155 μg/dL); renal dysfunction (BUN 79 mg/dL,

Importantly, splenectomy cures almost all patients with HS,

creatinine 4.97 mg/dL); hyperproteinemia (11.7 g/dL); elevatedeliminating anemia and hyperbilirubinemia and reducing the

LDH level (1356 U/L); hypoalbuminemia (2.1 g/dL); elevatedreticulocyte count to nearly normal. However, risks and bene-

C-reactive protein level (11.3 mg/dL); high beta-2-microglobulin

fits should be assessed carefully before splenectomy is done

level (11.1 mg/L); elevated IgG level (7425 mg/dL); abnormal[6]. Interestingly, HS has been only rarely described in associa-

serum free light chain ratio (0.01: kappa 8.8 mg/dL, lambda

tion with neoplasms such as hematological malignancies

1650 mg/L); and high uric acid level (26.2 mg/dL) (Table 1A).

including several cases of MM [7, 8].

A monoclonal IgG lambda peak was identified in serum

Here we present the first case of an HS patient with symp-

immunoelectrophoresis. Mild proteinuria was observed, andtomatic MM who underwent successful autologous PB stem

the Bence Jones protein urine test was positive. BM aspirate

cell harvest and transplantation procedures after splenectomy.

smears revealed marked proliferation of plasma cells (Fig. 1B).
Flow cytometric analysis showed that the plasma cells were

Case Report

positive for CD38, CD138, CD56, and monoclonal lambda lightchain markers (Table 1B). Fluorescent in situ hybridization

The patient is a 58-year-old man with a past medical history

analysis showed aberrant IgH-FGFR3 signals (17.0%) andof unspecified hemolytic anemia, and his mother, son, andD13S319 signals (6.0%) (Table 1B). Computed tomographydaughter also have been identified as having unspecified

revealed splenomegaly (spleen size: 16.0 × 9.5 cm) (Fig. 1C),

hemolytic anemia. He noticed a sore throat, fever, and inter-gallstones, heterogeneous skull density, and pneumonia.

mittent disturbance of consciousness, and was admitted toMagnetic resonance cholangiopancreatography revealed­

our hospital in October 2016. All laboratory findings arecholecystitis. In addition, no plasmacytoma was detected.
­­summarized in Table 1. Severe anemia (hemoglobin 3.6 g/dL),

Taken together, he was diagnosed with symptomatic MM

thrombocytopenia (platelet count 6.8 × 104/μL), spherocytosis,

IgG lambda type stage III, based on the revised internationaland erythrocyte rouleaux formation were observed in the PB

staging system.

(Table 1A; Fig. 1A). He also presented with altered liver func-

The patient was initially treated with BTZ/dexamethasone

Table 1A. Laboratory data including CBC, chemistry, and serology

Table 1B. Laboratory data including myelogram, flow
­cyto­metry analysis, G-banding, and FISH analysis

CBC

Serology

NCC

5.6 × 104/μL

Flow cytometry analysis CD38 gating<15/μL

CD19

0.3%

CD20

0.2%

Chemistry

WBC
Seg
Stab

7500/μL

TP

11.7 g/dL

IgG

7425 mg/dL

MgK

73.5%

Alb

2.1 g/dL

IgA

4 mg/dL

Myelogram

4 mg/dL

Blast

0.0%

CD49e

0.8%

Prom

0.9%

CD56

73.9%

Mye

14.1%

CD138

94.6%

Meta

2.4%

κ

0.1%

Stab

3.7%

λ

97.7%

Seg

10.2%

Eo

1.6%

G-banding

Ba

0.0%

46, XY [20]

Mo

3.8%

Macrophage

0.1%

FISH analysis

Lybl

0.0%

IgH-FGFR3 (+)

Lybl

0.0%

D13S319 (+)

Plasma

40.6%
0.0%

4.0%

T-Bil

6.3 mg/dL

IgM

Lym

7.5%

D-Bil

3.1 mg/dL

FLCκ

8.8 mg/L

Mo

13.0%

AST

866 U/L

FLCλ1650 mg/L

Eo

0%

ALT

496 U/L

κ/λ

0.01

Ba

0%

ALP

73 U/L
SPEP

IgG-λ type

4

RBC

130 × 10 /μL

LDH1356 U/L

Hb

3.6 g/dL

AMY

45 U/L

Ht

12.2%

NH3

155 μg/dL

Coombs test

MCV

93.8 fLUA

26.2 mg/dL

direct

(–)

MCH

27.7 pgGlu

245 mg/dL

indirect

(–)

MCHC

29.5%

BUN

79 mg/dL

Ret

48‰

Cre

4.97 mg/dL

PLT

6.8 × 104/μL

Na

128 mEq/L

K

5.0 mEq/L

Pro-E

Cl

91 mEq/L

Baso-E

0.8%

Ca

6.6 mg/dL

Poly-E

17.8%

β2-MG

11.07 mg/L

Ortho-E

0.2%

CRP

11.26 mg/dL

M/E

1.8

12

International Journal of Myeloma

Haptoglobin <10 mg/dL

vol. 8 no. 3 (2018)

PBSCT after splenectomy in MM with HS

Figure 1. Peripheral and bone marrow smear at diagnosis, preoperative abdominal computed tomography, and excised macroscopic spleen
specimen. A. Peripheral blood smear at diagnosis. Red arrows indicate spherocytes; blue arrows indicate red blood cell rouleaux formation. B.
Bone marrow smear at diagnosis shows a marked proliferation of atypical plasma cells. C. Computed tomography shows mild splenomegaly.
D. The excised macroscopic spleen specimen reveals splenomegaly.

Figure 2. Clinical course. Bd, bortezomib/dexamethasone; CyBorD, cyclophosphamide/bortezomib/dexamethasone; PBSCH, peripheral blood
stem cell harvest; HDT-ASCT, high-dose therapy and autologous stem cell transplantation; Hb, hemoglobin level; T-Bil, total bilirubin level.

as an induction regimen in October 2016. His clinical course

additional induction regimen in December 2016 and January

is shown in Figure 2. Subsequently, he received two cycles

2017. After completion of two courses of CyBorD treatment,of cyclophosphamide/BTZ/dexamethasone (CyBorD) as ansplenomegaly was thought to be a risk factor for splenicInternational Journal of Myeloma

vol. 8 no. 3 (2018)13

FURUYA et al.

rupture in the mobilization process using G-CSF; thus,­

ture. Spontaneous rupture of the spleen is an uncommon­laparoscopic splenectomy and cholecystectomy were done

complication in patients with MM and immunoglobulin lightin January 2017 (excised spleen size: 18.2 × 12.5 × 7.2 cm)

chain systemic (AL) amyloidosis [10]. Moreover, Lessi et al.

(Fig. 1D). After one additional cycle of CyBorD treatment,

reported a case of spontaneous splenic rupture following stemhe obtained a partial response before the first mobilization.

cell mobilization with G-CSF and plerixafor in AL amyloidosis

Thereafter, first mobilization was performed using G-CSF[10]. Therefore, G-CSF mobilization in a patient with MM and2alone (400 μg/m /day, s.c.) for 4 days. However, he did not

HS involves a significant risk of splenic rupture. Although ourmobilize sufficient CD34+ cells for transplantation (7.52 cells/μL

case showed splenomegaly, we decided to conduct splenec-in 2 days), and harvest could not be done. Subsequently,

tomy before the mobilization process, because the possible

we conducted a s­econd mobilization using G-CSF (400cause of this splenomegaly may have been due to both2μg/m /day, s.c.) for 6 days and plerixafor (0.24 mg/kg/day,­amyloidosis and HS. We believe that splenectomy was thes.c.) for 2 days. Finally, he mobilized sufficient CD34+ cells

best way to avoid splenic rupture in this case.

6

for transplantation (66.14 cells/μL; 2.414 × 10 cells/kg in 2

Next, many isolated mutations have been identified in thedays). Thereafter, he received HDT (melphalan 200 mg/m2)

genes encoding membrane proteins including ankyrin, band 3,

supported by ASCT in April 2017. As a result, he attained aβ spectrin, α spectrin, and protein 4.2. Whether these muta-

stringent complete response as of May 2017. He is now

tions influence HSC potential or mobilization efficiency isreceiving maintenance therapy with lenalidomide and con­unknown. Although we did not analyze the presence of thesetinues to have a stringent complete response.

mutations in our patient, some mutations may influence HSCs
or the BM microenvironment, resulting in poor mobilization

Discussion

efficiency. Further case reports and studies are warranted tounveil the detailed mechanisms associated with HSC mobiliza-

We experienced a very rare case of MM with HS. We

tion insufficiency in MM with HS.

reviewed the literature on monoclonal gammopathy of

In conclusion, the clinical manifestations of HS include­undetermined significance or MM and HS, and found two­splenomegaly, which is thought to be a risk factor for splenic

reports. First, Schafer et al. reported two cases of monoclonalrupture in the mobilization process using G-CSF. Although

gammopathy in patients with HS, and proposed a possible

the mobilization efficiency of PB stem cells following splenec-

pathogenetic relationship in which chronic reticuloendo­

tomy is unknown, ASCT after using G-CSF in combination

thelial stimulation due to extravascular hemolysis may foster

with plerixafor after splenectomy may be safe and effective.

neoplastic transformation of immunocytes in patients withHS, ultimately leading to the development of monoclonal

Authorship

gammopathy [8]. Next, Hattori et al. reported a 71-year-old
Japanese male with Bence Jones-type MM associated with

D.F. and R.S. analyzed the clinical status of the patient,

HS [7]. However, neither splenectomy nor ASCT was per­­analyzed the data, and prepared the manuscript; J.A., D.O.,

formed in this case. To the best of our knowledge, this is the

H.M., A.I., S.S., S.K., K.H., H.K., and Y.O. analyzed the data; K.A.

first case of MM with HS with s­ uccessful autologous PB stem

­analyzed the clinical status of the patient, analyzed the data,cell harvest and transplantation after splenectomy.

and prepared the manuscript.

Temporary splenic enlargement can occur during G-CSF
administration both in healthy donors and in patients with

Conflicts of Interest

hematological malignancies [9]. In addition, splenic enlargement, administration of G-CSF, and hematopoietic stem cell

The authors declare no competing financial interests.

transplantation are considered risk factors for splenic rupture[10]. Reported estimates of the incidence of splenic rupture

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