leukocytosis, eosinophilia and/or basophilia, imma-

ture myeloid precursors in blood, splenomegaly,

fibrosis or huge megakaryocytes. Although some

patients with thrombocytosis and ringed sideroblasts

have been classified as having essential thrombo-

cythemia or prefibrotic chronic idipathic myelo-

fibrosis in previous reports [10], in our opinion,

these 11 cases should be not classified within any of

these entities because ringed sideroblasts are not

found in classic MPD.

In summary, all 11 patients presented features of

both MDS and MPD and would be better classified

as MDS/MPD rather than as RARS. Of importance,

none of these 11 patients satisfies the criteria of

CMML, aCML or JCML, which comprise MDS/

MPD characterized by the predominance of neutro-

philic or monocytic effective proliferation, but

usually with a normal or decreased platelet count.

By contrast, these 17 patients are characterized by

megakaryocytic proliferation and thombocytosis with

leukocyte counts that are normal or only mildly

increased. In our opinion, these patients may

constitute one subgroup within the MDS/MPD U;

MDS/MPD with thombocytosis.

Tomas Pintado

Cros. Departamento de Hematologıa y Hemoterapia

Hospital General Universitario Gregorio Maranon

Dr Esquerdo 46, Madrid 28007, Spain

E-mail: ISABELALFAAN@telefonica.net

References

1. Greenberg PL. Myelodysplastic syndrome. In: Hoffman R,

Benz EJ Jr, Shattil SJ, Furie B, Cohen HJ, Silberstein LE,

McGlave P, editors. Hematology: Basic Principles and

Practice, 3rd edn. Edinburgh: Churchill Livingstone; 2000.

pp. 1106 – 1129.

2. Bennett JM, Catovsky D, Daniel T, Flandrin G, Galton DA,

Gralnick HR, et al. FAB Cooperative Group: proposal for the

classification of the myelodysplastic syndromes. Br J Haematol

1982;51:189 – 199.

3. Harris NL, Jaffe ES, Diebold J, Flandrin G, Muller-Hermelink

HK, Vardiman J, et al. World Health Organization of

neoplastic diseases of the hematopoietic and lymphoid tissues:

report of the clinical advisory committee meeting. Airlie

House, Virginia, November 1997. J Clin Oncol 1999;17:

3835 – 3849.

4. Neuwirtova R, Mocikova K, Musilova J, Jelinek J, Havlicek F,

Michalova K, et al. Mixed myeloysplastic and myeloprolifera-

tive syndromes. Leuk Res 1996;20:717 – 726.

5. Vardiman JW. Myelodysplastic/myeloproliferative diseases:

Introduction. In: Jaffe ES, Harris NL, Stein H, Vardiman

JW, editors. World Health Organization Classification of

Tumours: Pathology and Genetics of Tumours of Haemato-

poietic and Lmphoid Tissues. Lyon: IARC Press; 2001.

pp. 47 – 48.

6. Bain B, Vardiman JW, Imbert M, Pierre R. Myelodysplastic/

myeloproliferative disease, unclassifiable. In: Jaffe ES, Harris

NL, Stein H, Vardiman JW, editors. World Health Organiza-

tion Classification of Tumours: Pathology and Genetics of

Tumours of Haematopoietic and Lymphoid Tissues. Lyon:

IARC Press; 2001. pp. 58 – 59.

7. Kushner JP, Lee GR, Wintrobe MM, Cartwright GE.

Idiopathic refractory sideroblastic anemia. Clinical and

laboratory investigation of 17 patients and review of the

literature. Medicine 1971;30:139 – 159.

8. Cabello AI, Collado RM, Ruiz A, Martınez J, Navarro I,

Ferrer R, et al. A retrospective analysis of the myelodysplastic

syndromes with thrombocytosis: reclassification of the cases by

WHO proposals. Leuk Res 2005;29:365 – 370.

9. Perez Sanchez I, Perez Corral A, Menarguez Palanca J,

Mayayo Crespo M, Escudero Soto A, Pintado Cros T.

Sideroblastic anaemia with reactive trombocytosis versus

myelodysplastic/myeloproliferative disease. Leuk Lymphoma

2003;44:557 – 559.

10. Schmitt-Graeff A, Thiele J, Zuk I, Michael Kvasnicka H.

Essential thrombocythemia with ringed sideroblasts: a hetero-

geneus spectrum of diseases, but not a distinct entity.

Haematologica 2002;87:392 – 399.

DOI: 10.1080/10428190500404894

Successful use of short-course high-dose methylprednisolone in a childwith acute myeloblastic leukemia (FAB M2) and myeloid tumor

EMEL OZYUREK1, BULENT ALIOGLU2, MEHMET COSKUN3, & NAMIK OZBEK4

1Department of Pediatric Hematology, 2Department of Pediatric Hematology, 3Department of Radiology, and 4Department

of Pediatric Hematology, Baskent University Faculty of Medicine, Ankara, Turkey

(Accepted 22 April 2005)

Extramedullary leukemia (EML) is defined as

leukemic infiltration of organs other than the liver,

spleen, and lymph nodes. This neoplasm most often

arises in bone, the orbit, the central nervous system,

the gingivae, and the skin [1 – 4]. Patients with EML

frequently undergo medical therapy, radiation

treatment, surgical decompression, or any combina-

tion of these interventions. Short-course (4 – 7 days)

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high-dose methylprednisolone (HDMP; 20 – 30 mg/

kg per day) has been successful for treating both

acute myeloid leukemia (AML) and EML in

children. The literature notes dramatic, rapid resolu-

tion of extramedullary infiltration with this therapy

[3,4 – 6].

A 15-year-old adolescent boy was admitted to our

hospital with a 1-month history of fever, night sweats,

pruritus, weight loss, hearing loss, and ear, abdom-

inal and back pain. His family history and past

medical history were unremarkable. The patient

preferred to remain in supine position due to severe

pain in his lumbar and abdominal regions. He was

able to walk with support. Ophthalmologic examina-

tion revealed exophthalmos, restricted lower and

upper gaze, optic disc edema, and subconjunctival

and intraretinal hemorrhage. It was not possible to

do complete motor and sensory neural examinations

because of the severity of the pain. The Achilles’

reflexes were absent bilaterally. There was no urinary

retention, and anal sphincter tone was normal.

General musculoskeletal system assessment revealed

marked local tenderness over the spinous processes

of the lumbar vertebrae. The patient’s liver was

palpable 2 cm below the costal margin, but the spleen

was not palpable. Other system examinations were

normal.

The initial complete blood count showed hemo-

globin 6.7 g/dl, white blood cell count 3.26 109/l

(36% blasts on peripheral smear), and platelet count

186 109/l. All biochemical test results were normal.

Bone marrow examination revealed 50% myelo-

blasts, and based on this the patient was diagnosed

with French – American – British (FAB) AML-M2.

The findings on cytogenetic analysis of the bone

marrow were 46,XY with translocation (8;21)

(q22;q22). Abdominal computed tomography (CT)

revealed a 66 36 1.5-cm solid lesion in the

presacral region. The scan also showed multiple

soft-tissue lesions of maximum 1.5-cm diameter

within the lumbar (L4-5) and sacral regions of the

spinal canal. Orbital magnetic resonance imaging

(MRI) showed solid lesions in the superior portions

of both orbits (right, 56 1.26 3.6 cm transverse

[T]6 cranio-caudal [CC]6 anterior-posterior [AP];

left, 56 1.86 3.6 cm T6CC6AP) and a solid

lesion measuring 26 1.4 cm at the junction of the

zygomatic and squamous processes of the right

temporal bone (Figure 1a). Audiometric testing

indicated sensorineural hearing loss, and MRI of

the internal acoustic canal was normal.

Initially, we administered intravenous meperidine

hydrochloride to control the pain that was caused by

the cord compression. Before induction therapy, the

patient received a single intravenous dose of methyl-

prednisolone 30 mg/kg per day for 3 days. This

resulted in significant improvement in his abdominal

pain, ear pain, back pain, and ophthalmologic

findings, as reflected by reduced need for meperidine

hydrochloride. Following HDMP treatment, the

patient was switched to the AML-BFM 93 treatment

protocol [7]. Resolution of a major portion of the

extramedullary masses was seen on CT of the lumbar

vertebrae, taken 3 days after initiation of therapy and

there was a significant decrease in the presacral

masses (2.56 1 cm). Sizes of multiple soft tissue

lesions within the lumbar and sacral regions of

the spinal canal were also observed to have declined.

A decrease in the size of the solid lesions of

both superior orbita [right, 2.86 0.66 2.2 cm

Figure 1. Orbital magnetic resonance imaging of solid lesions in the superior portions of both orbits (a) before treatment and (b) after

therapy.

924 Letters to the Editor

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(T6CC6AP); left, 2.86 0.66 1.8 cm (T6CC6AP)] and a solid lesion at the junction of

zygomatic and squamous processes of the right

temporal bone (1.46 1.1 cm) were detected on

orbital MRIs taken 3 days after initiation of therapy

(Figure 1b). At day 5 of HDMP and day 2 of the

AML-BFM 93 treatment protocol there were no

blasts in the peripheral blood. Spinal lesions dis-

appeared totally 21 days after the completion of

HDMP treatment. Ten months after diagnosis the

patient is in complete remission and continues to

receive maintenance therapy.

In a previous study, a wide range of EML incidence

has been reported in childhood AML. Although there

is a frequent association between EML and FAB

AML-M4 and AML-M5 subtypes, it has also been

reported in AML-M2 t(8;21) (q22;q22) as in our

patient [1 – 4]. Most commonly EML is described as

a single involvement site, but it has been also

reported in multiple sites as in the present case. In

addition, only a small fraction of these tumors

involve the spinal cord [1,8,9].

Chemotherapy, radiation therapy, surgical decom-

pression, or any combination of these interventions

is frequently used in patients with EML. Since

complete remission with aggressive chemotherapy is

observed in most cases, routine irradiation of EML

sites is not necessary [1]. Surgery is generally reserved

for cases with acute spinal cord compression or

neurological symptoms [8,9]. Although our patient

had neurological findings due to spinal cord compres-

sion, short-course HDMP was chosen to decrease the

size of masses because of successful responses to

HDMP reported in patients with EML [3,4 – 6].

Following the administration of short-course HDMP

a dramatic decrease in peripheral blasts and a remark-

able reduction in the size of EML was detected.

Hicsonmez et al. [4] described two children with

AML-M2 who presented with ocular and mandibu-

lar EML and who were successfully treated with

HDMP. Recent studies have demonstrated that

HDMP can induce terminal differentiation and

apoptosis of myeloid cells in children with different

subtypes of AML in vivo and in vitro [5,10,11]. They

also demonstrated that addition of HDMP to

cytotoxic chemotherapy increased the remission rate

and prolonged the duration of remission in children

with AML, and also improved the outcome of these

children who presented with extramedullary infiltra-

tion. Recently, glucocorticoid induced apoptosis has

been shown to occur in a dose-dependent manner in

AML cell lines with a t(8;21) [5].

In general, HDMP administration was effective

and well tolerated without significant side effects in

our patient. We conclude that as a single agent

HDMP treatment followed by classic chemotherapy

protocols is an alternative way to treat AML patients

with EML.

Bulent Alioglu, MD

Baskent University

6. Cad. 72/3 Bahcelievler

06490, Ankara, Turkey

Tel: 90 312 2130776. Fax: 90 312 2157597

E-mail: bulenta@baskent-ank.edu.tr

References

1. Dusenbery KE, Howell WB, Arthur DC, Alonzo T, Lee JW,

Kobrinsky N, et al. Extramedullary leukemia in children with

newly diagnosed acute myeloid leukemia. A report from the

Children’s Cancer Group. J Pediatr Hematol Oncol 2003;

25:760 – 768.

2. Bisschop MM, Revesz T, Bierings M, van Weerden JF,

van Wering ER, Hahlen K, et al. Extramedullary infiltrates at

diagnosis have no prognostic significance in children with

acute myeloid leukaemia. Leukemia 2001;15:46 – 49.

3. Hicsonmez G, Cetin M, Tuncer AM, Yenicesu _I, Aslan D,

Ozyurek E, et al. Children with acute myeloblastic leukemia

presenting with extramedullary infiltration: the effects of high-

dose steroid treatment. Leuk Res 2004;28:25 – 34.

4. Hicsonmez G, Cetin M, Aslan D, Ozyurek E. The role of

short course of high-dose methylprednisolone in children with

acute myeloblastic leukemia (FAB M2) presented with

myeloid tumor. Ped Hematol Oncol 2003;20:373 – 379.

5. Hicsonmez G, Tuncer M, Toksoy HB, Yenicesu _I, Cetin M.

Differentiation of leukemic cells induced by short-course high-

dose methylprednisolone in children with different subtypes of

acute myeloblastic leukemia. Leuk Lymphoma 1999;33:573 –

580.

6. Shimohakada Y, Shinohara K, Fukuda N. Remission of acute

myeloblastic leukemia after severe pneumonia treated with

high-dose methylprednisolone. Int J Hematol 2001;74:173 –

177.

7. Creutzig U, Ritter J, Zimmermann M, Reinhardt D,

Hermann J, Berthold F, et al. Improved treatment results in

high-risk pediatric acute myeloid leukemia patients after

intensification with high-dose cytarabine and mitoxantrone:

Results of study acute myeloid leukemia-Berlin-Frankfurt-

Munster 93. J Clin Oncol 2001;19:2705 – 2713.

8. Landis DM, Aboulafia DM. Granulocytic sarcoma: An

unusual complication of aleukemic myeloid leukemia causing

spinal cord compression. A case report and literature review.

Leuk Lymphoma 2003;44:1753 – 1760.

9. Mostafavi H, Lennarson P, Traynelis VC. Granulocytic

sarcoma of the spine. Neurosurgery 2000;46:78 – 84.

10. Miyoshi H, Ohki M, Nakagawa T, Honma Y. Glucocorticoids

induce apoptosis in acute leukemia cell lines with a

t(8;21) chromosome translocation. Leuk Res 1997;21:

45 – 50.

11. Ozbek N, Erdemli E, Hicsonmez G, Okur H, Tekelioglu M.

Effects of methylprednisolone on human myeloid leukemic

cells in vitro. Am J Hematol 1999;60:255 – 259.

DOI: 10.1080/10428190600813259

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