LETTER TO THE EDITOR

Frequent extramedullary recurrence of isolated myeloidsarcoma in the long-term follow-up

Yinjun Lou & Wenbin Qian & Haitao Meng & Yin Tong &

Jie Jin

Received: 3 September 2011 /Accepted: 6 December 2011 /Published online: 23 February 2012# Springer-Verlag 2012

Dear Editor,Myeloid sarcoma (MS) is a rare disease that presents as anextramedullary tumor composed of immature myeloid cells[1]. MS most commonly occurs concomitantly or followingof acute myeloid leukemia (AML), myeloproliferative dis-eases, or myelodysplastic syndromes [2]. Occasionally, iso-lated MS may occur as an isolated tumor without evidenceof leukemia [3, 4]. Because of its uncommon and variedclinical presentations, isolated MS has been described onlyin limited case reports [5, 6]. The prognosis and optimaltreatment of isolated MS are not fully understood. Forfurther clarification of its clinicopathological characteristics,therapeutic regimens, recurrence, and the follow-up non-leukemic period, here we retrospectively report a series of12 patients.

We conducted a retrospective study in patients (≥13 years)who were admitted to our Department of Hematology. Wesearched for isolated MS frommedical database from January2004 toMay 2011. Routine histologic and immunohistochem-ical studies were reviewed at our hospital to confirm thediagnosis. Bone marrow aspiration has been performed toexclude the possibility of leukemia. Their medical recordswere analyzed. The follow-up information was obtained bycontacting the physicians, the patients, or their family mem-bers. The clinical response of complete remission (CR), partialremission (PR), or treatment failure was defined as describedby a previous publication [6]. The cases were analyzed forage, sex, clinical presentation, treatment regimens, andfollow-up outcomes. In addition, to compare the frequency

and age distribution of the disease, also all de novo AMLpatients (≥13 years) were searched.

In total, 12 cases with isolated MS were identified in thestudy. A summary of patient demographics and character-istics of each case appeared in Table 1. Four patients weremales and eight were females. The median age of the 12patients was 39.8 with a range of 19–62 years. The com-monest sites of MS presentation in our male cases were thelymph node and soft tissues (4/4). Surprisingly, the repro-ductive organs (7/8) were the most common involved sitesin our female patients (breast, three cases; vagina, two cases;and cervix, two cases). The total number of de novo AML inthis time interval was 1,408. The age of the AML patientsranged from 13 to 85 years, with a median age of 44.2 years,and 784 patients were male and 624 patients were female.Isolated MS occurred in 0.85% (12/1,408) of patients withAML in our center. The incidence of isolated MS in ourdata was lower (0.85%) than that of a previous report(1.4%) [6].

For the treatment of our cases, local tumor excisionwas performed in five cases. Patient 5 got PR after onecycle of DA (daunorubicin+cytarabine) induction thera-py but refused further therapy and was lost to follow-up. All the other cases were administered with systemchemotherapy after the diagnoses. Patient 1 was givenseven cycles of cyclophosphamide, doxorubicin, vincris-tine, and prednisone therapy because of misdiagnosingas lymphoma. All other ten cases were given AML-typetherapy, usually DA-based induction chemotherapy. Sub-sequently, five to seven additional cycles of consolida-tion therapy was continued. Patient 4 was given onecycle of high-dose cytarabine intensive therapy. Finally,in the initial therapy period, ten patients achieved CR(83.3%), and two patients showed PR (17.7%); no treat-ment failure was observed.

Y. Lou :W. Qian :H. Meng :Y. Tong : J. Jin (*)Department of Hematology, Institute of Hematology, The FirstAffiliated Hospital of Zhejiang University, School of Medicine,79# Qingchun Road,Hangzhou, Zhejiang Province, People’s Republic of China 310003e-mail: zjuhematology@163.com

Ann Hematol (2012) 91:1317–1319DOI 10.1007/s00277-011-1386-x

Tab

le1

Sum

maryof

patient

characteristicsandrespon

seto

therapy

No.

Age/sex

Site(s)

Immunohistochem

istry

Initial

treatm

ent/response

Rem

ission

duratio

n(m

onths)/relapse

site(s)

Recurrent

treatm

ent/

respon

seTim

eto

leukem

ia(m

onths)

Follow-up

(months)/outcome

153

/FVagina

CD43+,CD45RO+,MPO+,

CD34+/−,CD3−

,CD20−,

CD15−

Surgery

andchem

otherapy/

CR

62/right

orbit

Chemotherapy/PR

–71

/PR(lostto

follo

w)

219

/FRight

breast

MPO+,CD43+,CD20−,CD3−

,CD79a−

,CD

117−

,CD34−

Surgery

andchem

otherapy/

CR

––

–>36

/CR

332

/MLym

phno

de,softtissue

MPO+,CD43+,CD117+

,CD34−,CD10−,CD3−

,TdT

−,

CD20−,CD79

a−,CD45

RO−,

Ki6770

%

Chemotherapy/CR

25/ly

mph

node,soft

tissue

Chemotherapy/PR

–>36

/PR

437

/FRight

breast,lymph

node

MPO+,LCA+,CD34−,CD117−

,CD15−,CD20−,CD3−

,TdT

−Surgery

andchem

otherapy/

CR

6/leftbreast,lymph

node

Chemotherapy/failure

910/dead

562

/MLym

phno

deandskin

MPO+,CD45+,CD7+

,CD2−

,CD3−

,CD20−,CD79α−

,CgA

−Chemotherapy

(one

cycle,

then

refusedto

continue)/PR

––

–3/PR(lostto

follo

w)

642

/MLym

phno

de,soft

tissue

MPO+,CD117+

,CD45+,CD3−

,CD20−TdT

−,CD34−

Chemotherapy/CR

12/ly

mph

node,soft

tissue

Chemotherapy/PR

–18

/dead

739

/FVagina

MPO+,CD43+,CD117+

,CK−,

CD138−

,CD34−,DES−,HMB−,CD15−

Chemotherapy/CR

15/vagina

Chemotherapy

and

radiation/failu

re24

32/dead

835

/FLeftbreast

MPO+,CD34+,CD117+

,CD10−,

CD15−,CD30−,Syn−,CgA

−,

CD38−,CD13

8−,EBV−

Surgery

andchem

otherapy/

CR

95/right

breast

Surgicaland

chem

otherapy

/CR

–>98

/CR

941

/FCervix

MPO+,CD43+,CD117+

,CD20−,

CD3−

Chemotherapy/CR

––

–>12

/CR

1031

/FCervix

MPO+,LCA+,CD45RO+,CD20−,

CD79a−

,TdT

−,CD5−

,CD10−,

CD3−

,Ki-67

+90

%

Chemotherapy/CR

––

–>20

/CR

1157

/FLym

phno

deMPO+,CD117+

,CD43+,CD34

+,

CD3−

,CD20−,CD10−,CD15−,

TdT

−

Chemotherapy/PR

––

–>12

/PR

1233

/MSofttissue

CD117+

,CD43+,CD34+,MPO−,

CD3−

,CD20−,CD79a−

Surgery

andchem

otherapy/

CR

19/softtissue

Chemotherapy/PR

–>23

/PR

1318 Ann Hematol (2012) 91:1317–1319

However, extramedullary MS relapse developed in sevenout of nine CR patients (77.8%) in the follow-up. (Patient 5was lost). The mean duration of first CR until relapse was33.4 months, with range from 6 to 62 months. The MSrecurrence was also confirmed by hispathology and immu-nochemistry. Bone marrow was reevaluated to exclude thepossibility of overt leukemia. Interestingly, two patientswith MS originally from the breast had a relapse at the otherside of the breast. Four patients had a relapse on the primaryMS sites. Patient 1 relapsed at a remote site (from vagina toorbit). The treatment for relapsed MS was very challenging.Patient 7 was given radiation therapy and chemotherapy.Patient 8 had surgical removal and received chemotherapy.The remaining five patients were administered chemothera-py. Usually, more intensive combination chemotherapy in-cluding anthracyclines (idarubicin, mitoxantrone, andaclarubicin), cytarabine, etoposide, homoharringtonine, etc.were given. The treatment response for recurrent MS wasmoderate; only one patient achieved CR again. Five patientsgot PR. Patient 6 got PR but died of complication of che-motherapy. Two patients (patients 4 and 7) were refractoryto chemotherapy, and both progressed to AML. Both of theovert leukemia patients were failure to salvage chemothera-py and died of complications.

Clinical follow-up was available for ten patients. Patient1 and patient 5 were lost to follow-up. At last follow-up,seven patients were known to be still alive. Two patients(patients 4 and 7) had died of complication of leukemia(FAB classification M2) at 10 and 32 months, respectively.Patient 6 died of complication of chemotherapy. Survival ofthe seven patients alive at last follow-up was between 12and 98 months, with three patients being still in first and onepatient in second CR. The median follow-up of survivingpatients was 33.8 months.

Generally, patients with isolated MS may subsequentlydevelop AML within 1 year (range, 5–12 months), and theirprognosis is poor [2, 6, 7]. The nonleukemic period in thisstudy was longer than previous reports [3, 7, 8]. The treat-ment results suggested that our standard AML-type chemo-therapy prolonged the nonleukemic period in a subset ofpatients. However, routine chemotherapy could maintain thedisease, but it is inadequate. The study indicates a high rateof extramedullary recurrence of MS in the follow-up non-leukemic period before progression to leukemia. To ourknowledge, there are no reports about the extramedullaryrelapse rate of MS. Interestingly, four patients relapsed at

their initial site of manifestation. It would be rational tocombine radiation therapy as a consolidation treatment forisolated MS [9]. The long-term outcomes were still undesir-able due to the frequent recurrence and then refractory tochemotherapy. Therefore, stem cell transplantation or clini-cal trials need be considered for some patients to achievestable remission and cure the disease [10].

Acknowledgments This work was supported by the National Natu-ral Science Foundation of China (no. 30700972). We thank the pathol-ogists in our hospital for their work on the pathology andimmunohistochemistry.

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