Juvenile Myelomonocytic Leukemia Associated with Neurofibromatosis and Complicated by Hemophagocytic Syndrome

Authors: E. Bubanská 1;  L. Plank 2;  P. Szépe 2;  P. Mesár 1;  P. Bician 1
Authors‘ workplace: Klinika pediatrickej onkológie a hematológie SZU pri DFNsP, Banská Bystrica prednostka h. doc. MUDr. E. Bubanská, PhD. 1;  Ústav patologickej anatómie a Konzultačné centrum bioptickej diagnostiky JLF UK a MFN, Martin prednosta prof. MUDr. L. Plank, CSc. 2
Published in: Čes-slov Pediat 2008; 63 (1): 24-32.
Category: Case Report


Juvenile Myelomonocytic Leukemia (JMML) is a disease from the spectrum of myelodysplastic/myeloproliferative diseases and it is also included in the category of malignant diseases presently classified in histiocytic diseases. Hemophagocytic syndromes classified in histiocytic diseases are included into the diseases of variable biologic behavior. The association of myelomonocytic leukemia (JMML) with neurofibromatosis type 1 (NF 1) has been known. The objective of this contribution is to demonstrate, in the present case of a patient with JMML and NF 1, complicated by a simultaneous secondary hemophagocytic syndrome – VAHS or MAHS (Virus associated hemophagocytic syndrome, or Malignancy associated hemophagocytic syndrome), the problems in differential diagnosis as well as in the therapy of combinations of these two serious histiocytic diseases.

The case and results:
The disease became manifest in a two and three quarter year old boy with a clinical picture of a febrile state with bronchopneumonia and hepatosplenomegaly, icterus, the blood count with leukocytosis, thrombocytopenia and anemia, the differential blood could being characterized by a marked leukocytosis with marked monocytosis and the finding of younger developmental forms of granulocytes and blasts. The simultaneously present hypoproteinemia, hypofibrinogenemia and global coagulopathy, the presence of active virus infection (Herpes simples and Coxsackie B1) as well as multiplication of macrophages in bone marrow and the signs of hemophagocytosis resulted in the diagnosis of a simultaneous VAHS. In spite of the therapy aimed at influencing malignity as well as hemophagocytic syndrome the course of the disease was rapid and fatal.

JMML without successful allogenic transplantation is fatal in almost 100% of cases. VAHS, if not therapeutically influenced, may also result in death of the patient. In the situation of a lacking donor and rapid course of the two simultaneous complications, the child could not be saved.

Key words:
juvenile myelomonocytic leukemia, neurofibromatosis type 1, secondary hemophagocytic syndrome – VAHS (Virus associated hemophagocytic syndrome)


1. Hasle H, Niemeyer CM, Chessells JM, et al. A pediatric approach to the WHO classification of myelodysplastic and myeloproliferative diseases. Leukemia 2003;17(2): 277–282.

2. Mayer J, Starý J. Leukemie. 1. vyd. Praha: Grada Publ., 2002: 236–237.

3. Niemeyer CM, Arico M, Basso G, et al. Chronic myelomonocytic leukemia in childhood: a retrospective analysis of 110 cases. European Working Group on Myelodysplastic Syndromes in Childhood (EWOG – MDS). Blood 1997;89(10): 3534–3543.

4. Chang AE, Ganz PA, Haydes DF, et al. (eds.). Oncology: an evidence-based approach. 1st ed. New York: Springer, 2006: 517–519.

5. Janka G, Imashuku S, Elinder G, et al. Infection- and malignancy-associated hemophagocytic syndromes. Secondary hemophagocytic lymphohistiocytosis. Hematol. Oncol. Clin. North Am. 1998;12(2): 435–444.

6. Janka GE, Schneider EM. Modern management of children with haemophagocytic lymphohistiocytosis. Br. J. Haematol. 2004;124(1): 4–14.

7. Sugita K, Kurumada H, Eguchi M, et al. Human herpesvirus 6 infection associated with hemophagocytic syndrome. Acta Haematol. 1995;93(2–4): 108–109.

8. Favara BE, Feller AC, Pauli M, et al. Contemporary classification of histiocytic disorders. The WHO Committee On Histiocytic/Reticulum Cell Proliferations. Reclassification Working Group of The Histiocyte Society. Med. Pediatr. Oncol. 1997; 29(3): 157–166.

9. Henter JI, Arico M, Egeler RM, et al. HLH-94: a treatment protocol for hemophagocytic lymphohistiocytosis. HLH Study Group of the Histiocyte Society. Med. Pediatr. Oncol. 1997;28(5): 342–347.

10. Side LE, Emanuel PD, Taylor B, et al. Mutations of the NF1 gene in children with juvenile myelomonocytic leukemia without clinical evidence of neurofibromatosis, type 1. Blood 1998;92(1): 267–272.

11. Shannon KM, O’Connell P, Martin GA, et al. Loss of the normal NF1 allele from the bone marrow of children with typ 1 neurofibromatosis and malignant myeloid disorders. N. Engl. J. Med. 1994;330(9): 597–601.

12. Shin HT, Harris MB, Orlow SJ. Juvenile myelomonocytic leukemia presenting with features of hemophagocytic lymphohistiocytosis in association with neurofibromatosis and juvenile xantogranulomas. J. Pediatr. Hematol. Oncol. 2004;26(9): 591–595.

13. Pinkel D. Differentiating juvenile myelomonocytic leukemia from infectious disease. Blood 1998;91(1): 365–367.

14. Craig FE, Clare CN, Sklar JL, et al. T-cell lymphoma and the virus-associated hemophagocytic syndrome. Am. J. Clin. Pathol. 1992;97(2): 189–194.

15. Klein A, Corazza F, Demulder A, et al. Recurrent viral associated hemophagocytic syndrome in a child with Langerhans cell histiocytosis. J. Pediatr. Hematol. Oncol. 1999;21(6): 554–556.

16. Starý J, Housková J, Špíšek R, et al. Hemofagocytující lymfohistiocytóza – diagnostické a léčebné dilema. Čes.-slov. Pediat. 2004;59(2): 70–82.

17. Filipovich AH. Hemophagocytic lymphohistiocytosis: a lethal disorder of immune regulation. J. Pediatr. 1997;130(3): 337–338.

18. Ravelli A. Macrophage activation syndrome. Curr. Opin. Rheumatol., 14, 2002;14(5): 548–552.

19. Kashiwagi Y, Kawashima H, Sato S, et al. Virological and immunological characteristics of fatal virus-associated haemophagocytic syndrome (VAHS). Microbiol. Immunol. 2007;51(1): 53–62.

20. Starý J, Hrodek O, Housková J. Histiocytární syndromy v dětském věku. Čs. Pediat. 1990,45(10): 577–581.

Neonatology Paediatrics General practitioner for children and adolescents
Forgotten password

Don‘t have an account?  Create new account

Forgotten password

Enter the email address that you registered with. We will send you instructions on how to set a new password.


Don‘t have an account?  Create new account