Pediatric Hematology Oncology Journal 1 (2016) 56e57
Contents lists available at ScienceDirect
Pediatric Hematology Oncology Journal
journal homepage: https://www.elsevier.com/journals/pediatric-
hematology-oncology-journal/
Successful management of granulocytic sarcoma with concurrent
hemophagocytic lympho histiocytosis in a child
Keywords:
Granulocytic sarcoma
HLH
AML
To the editor:
Granulocytic sarcoma (GS) is rare extra-medullary tumor
composed of immature granulocytic cells has reported incidence
of 3.1% in patients with acute myeloid leukemia (AML) [1]. Malig-
nancy associated hemophagocytic lymphohistiocytosis (HLH) usu-
ally occurs at initial presentation or soon after starting
chemotherapy [2]. The diagnosis is challenging due to masking of
HLH manifestations by the malignancy itself or because the find-
ings of these two processes may be indistinguishable [2,3]. Seven
cases of AML concomitant with HLH in children have been reported
in literature but none with GS [4e6]. Of these only 3 survived (stem
cell transplant-2 and chemotherapy-1). Here we report successful
management of a case of GS with HLH.
A 6-year-old female presented with headache, proptosis of the
right eye and a mass in the right nasal cavity. MRI para-nasal si-
nuses revealed a mass in the right maxillary cavity extending into
the nasal choana. Biopsy of the mass was suggestive of GS. Bone
marrow examination revealed marrow infiltration with blast cells
(34%) consistent with acute myeloid leukemia (AML-M2). On
Flow Cytometry blasts expressed cytoplasmic MPO-66% and
CD34-78% with dim to moderately bright CD117-63% and they
also showed dim to moderately bright CD33-59%, CD13-58%, HLA
DR-80% and CD15-55%.Blasts didn't express CD56. Cerebro-spinal-
fluid was negative for malignant cells. Her leukemia cells were
AML-ETO positive. She was started on treatment as per UK-AML-
XII protocol. After administration of first cycle of chemotherapy
(cytarabine-2 g/m2, daunorubicin-150 mg/m2, etoposide-500 mg/
m2) on day-11 she developed high grade fever which didn't subside
over next 4-weeks. She was pancytopenic (Hb5g/dl, Total leukocyte
count 450/ml and platelet count 8000/ml. Initially it was thought to
be due to febrile neutropenia. All blood cultures were sterile. How-
ever, serum ferritin-2260 ng/ml, triglycerides-268 mg/dl and SGPT-
Peer review under responsibility of Pediatric Hematology Oncology Chapter of In-
dian Academy of Pediatrics.
http://dx.doi.org/10.1016/j.phoj.2016.10.118
2468-1245/© 2016 Pediatric Hematology Oncology Chapter of Indian Academy of Pediatrics. Production and hosting by Elsevier B.V. This is an open access article under the
CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).
244U/L were raised which was attributed to HLH and related inves-
tigations fulfilled the 5 out of 8 criteria to diagnose HLH [7](fever,
pancytopenia, high ferritin, high serum triglycerides, and spleno-
megaly). We didn't perform a bone marrow to look for hemophago-
cytosis as our diagnosis was made with clinical and laboratory
investigations and deranged liver functions also favoured diagnosis
of HLH. All possible causes for HLH such as EBV, CMV and fungal
infection were negative. There was no family history of HLH. She
was started on dexamethasone-10 mg/m2 for 28 days as per HLH-
2004 protocol. She improved symptomatically and her ferritin, tri-
glycerides and SGPT also improved (Fig. 1). Bone marrow at the end
of induction was in complete remission (CR). The 2nd cycle was
modified (cytarabine-1.6 g/m2, daunorubicin-100 mg/m2,etopo-
side-500 mg/m2) and dose was split (50% each) into cycle 2A (day
1e8) and 2B (day 15e22). After 2nd cycle a repeat MRI showed
no residual maxillary mass and her AML-ETO was negative. In
consolidation phase, she was given 4-courses of high dose cytara-
bine (12 g/m2). After consolidation, she was given oral maintenance
chemotherapy for 1-year (etoposide 25 mg/m2/day and 6-
thioguanine 20 mg/m2/day for 3-weeks on and 1-week off/cycle).
Her HLH settled completely and she continues to be in CR at 24-
months from her diagnosis.
Nearly half of the patients develop HLH during treatment [8] as
seen in our patient. Presumably, inflammatory cytokines secreted
by malignant cells play an important role in the pathogenesis [9].
The diagnosis of malignancy associated HLH is usually difficult.
HLH manifestations may be masked or modified by the malignant
process or therapeutic measures, so early diagnosis might be
frequently delayed since the condition might be misinterpreted
as chemotherapy induced myelosupression with sepsis. In our
case initially we thought sepsis as a cause of persistent fever and
all septic work up was negative. It has been suggested that the un-
derlying immunodeficient state due to the malignancy, combined
with chemotherapy, predispose to infections and defects in T-cell
and NK-cell function, which trigger HLH [3]. High ferritin, trigylcer-
ides and SGPT took many months to normalise (Fig. 1) which again
indicated that infection was the unlikely cause of HLH in our case.
During 2nd induction, we reduced dose of daunorubicin and split
the cycle in two parts, which helped patient, recover early from
myelosupression. We didn't reduce dose of etoposide keeping in
mind its proven efficacy in HLH [7]. Maintenance therapy was
added as her ferritin was still high although she was in CR. For
this we chose low dose oral etoposide and 6-thioguanine which
has been used as metronomic chemotherapy with good effect in
AML [10].
 Y. Chopra et al. / Pediatric Hematology Oncology Journal 1 (2016) 56e57 57

Fig. 1. Laboratory parameters of hemophagocytic lympho histiocytosis during treatment of acute myeloid leukemia therapy.

HLH may manifest during antineoplastic treatment. Early diag- myeloblastic leukemia cases concomitant with hemophagocytic lymphohis-
tiocytosis and review of the literature. Ann Clin Lab. Sci 2013;43(1):85e90.
nosis and immediate initiation of adequate treatment are manda-
[6] Jinta M, Arai A, Yamamoto K, Sakashita C, Fukuda T, Miu T, et al. Acute pro-
tory to overcome this severe condition. myelocytic leukemia associated with hemophagocytic syndrome. Rinsho Ket-
sueki 2007;48(4):310e4.
Contributors' credit [7] Henter JI, Horne A, Arico M, Egeler RM, Filipovich AH, Imashuku S, et al. HLH-
2004: diagnostic and therapeutic guidelines for hemophagocytic lymphohis-
tiocytosis. Pediatr Blood Cancer 2007;48(2):124e31.
YRC-wrote the case, MR-review of literature, SPY-discussion. [8] Celkan T, Berrak S, Kazanci E, Ozyurek E, Unal S, Uçar C, et al. Malignancy-
associated hemophagocytic lymphohistiocytosis in pediatric cases: a multi-
center study from Turkey. Turk J Pediatr 2009;51(3):207e13.
Funding [9] Janka G, Elinder G, Imashuku S, Schneider M, Henter JI. Infection and malig-
nancy associated hemophagocytic sydromes: secondary hemophagocytic
Nil. lymphohistiocytosis. Hematol Oncol Clin North Am 1998;12(2):435e44.
[10] Tandon N, Banavali S, Menon H, Gujral S, Kadam PA, Bakshi A. Is there a role
for metronomic induction (and maintenance) therapy in elderly patients with
Conflict of interest acute myeloid leukemia? A literature review. Indian J Cancer 2013;50(2):
154e8.
All authors have nothing to disclose.
Yogiraj Chopra, Mohammed Ramzan, Satya Prakash Yadav*
References Pediatric Hematology Oncology & Bone Marrow Transplant Unit,
Department of Pediatrics, Fortis Memorial Research Institute,
[1] Muss HB, Moloney WC. Chloroma and other myeloblastic tumors. Blood Gurgaon, Haryana, 122001, India
1973;42:721e8.
[2] Janka GE, Schneider EM. Modern management of children with haemophago-
*
cytic lymphohistiocytosis. Br J Haematol 2004;124:4e14. Corresponding author.
[3] O'Brien MM, Lee-Kim Y, George TI, McClain KL, Twist CJ, Jeng M. Precursor B- E-mail address: satya_1026@hotmail.com (S.P. Yadav).
cell acute lymphoblastic leukemia presenting with hemophagocytic lympho-
histiocytosis. Pediatr Blood Cancer 2008;50:381e3.
[4] Lackner H, Urban C, Petra S, Benesch M, Moser A, Schwinger W. Hemophago- 21 August 2016
cytic lymphohistiocytosis as severe adverse event of antineoplastic treatment Available online 24 October 2016
in children. Haematologica 2008;93:291e4.
_
[5] Akyay A, Celkan T, Iskender G, Tukun A, Ogan C, Olcay L. Two acute