SEARCH

SEARCH BY CITATION

Keywords:

  • leukaemia;
  • leishmaniosis;
  • Kala Azar;
  • chemosensitivity

A 3-year-old boy was treated for acute lymphoblastic leukaemia (ALL) according to the UK Medical Research Council trial (XI) (Hill et al, 2004). At diagnosis, his family returned to the UK after living in Albania and Greece for several years. Remission induction was uncomplicated, but dose reduction of maintenance chemotherapy was required due to persistent neutropenia. Maintenance was recommenced, but was delayed after intensification blocks and tolerated only at reduced doses for short periods (Fig 1A). After the third intensification, upon clinical examination for persistent febrile neutropenia, splenomegaly was noted for the first time, but no infective agent or other cause was identified. Surprisingly, a scheduled surveillance bone marrow examination at week 79 (Fig  1A, red arrow), showed extensive intracellular Leishmania donovani amastigotes (Fig 1B). Visceral leishmaniasis (VL), Kala Azar, was diagnosed and the boy received a 4-week course of liposomal amphotericin B (LATCB). The spleen returned to a normal size and persistent fever settled. Maintenance chemotherapy was recommenced and tolerated well for the entire remaining treatment period, which was extended to 120 weeks to compensate for the previously compromised treatment. He remains well 7 years later.

image

Figure 1.  (A) Maintenance chemotherapy tolerance of the patient with visceral leishmaniasis before the diagnosis (red arrow) and after treatment with liposomal amphotericin B (LATCB, red line). (B) Evidence of extensive Leishmania donovani amastigotes (arrow) in a surveillance bone marrow at 79 weeks of leukaemia treatment (image taken with ×100 lens).

Download figure to PowerPoint

In this case, VL presented classically following a travel history to an endemic area, despite treatment for ALL with persistent fever, splenomegaly and pancytopenia causing poor chemo-tolerance (Fenech, 1997). Although we considered Leishmaniasis, the absence of amastigotes on repeat bone marrow smears for leukaemia surveillance was thought to be sufficient to exclude VL. Re-examination did not show amastigotes on any earlier bone marrow smear. Current literature indicates that bone marrow microscopy is not always diagnostic in VL during leukaemia treatment and immunosuppression (Grech et al, 2000; Sirvent-von Buelzingsloewen et al, 2004). Now we also include molecular microbiological assays in case investigations, when the history and clinical findings are suggestive of VL.

This case demonstrates the profound effect of persistent infection on chemo-tolerance, which could compromise effective therapy and prognosis of the malignancy. Therefore, persistent unusual infections should be considered as treatable causes of poor chemo-tolerance, even after a long period of immunosuppressive treatment (79 weeks in our patient). Although chemotherapy might have had an effect on amastigotes, and empirical short courses of LATCB for febrile neutropenia may have led to partial control and delay of the diagnosis, immunosuppression did not result in overwhelming VL. In view of increasing individual travel activity, we are concerned about the impact of unusual parasitic infection on haemato-oncological practice. Given the difficulties in reaching a diagnosis in our patient, the problem of opportunistic VL in cancer patients might be more common than previously thought.

Acknowledgements

  1. Top of page
  2. Acknowledgements
  3. References

We are grateful to the family for allowing us to publish this case. SM is a CRUK Clinician Scientist.

References

  1. Top of page
  2. Acknowledgements
  3. References
  • Fenech, F.F. (1997) Leishmaniasis in Malta and the Mediterranean basin. Annals of Tropical Medicine and Parasitology, 91, 747753.
  • Grech, V., Vella, C. & Lenicker, H. (2000) Absence of bone marrow amastigotes in a child with kala-azar and acute lymphoblastic leukaemia. Annals of Tropical Paediatrics, 20, 237238.
  • Hill, F.G., Richards, S., Gibson, B., Hann, I., Lilleyman, J., Kinsey, S., Mitchell, C., Harrison, C.J., Eden, O.B. & The UK Medical Research Council Working Party on Childhood Leukaemia (2004) Successful treatment without cranial radiotherapy of children receiving intensified chemotherapy for acute lymphoblastic leukaemia: results of the risk-stratified randomized central nervous system treatment trial MRC UKALL XI (ISRC TN 16757172). British Journal of Haematology, 124, 3346.
  • Sirvent-von Buelzingsloewen, A., Marty, P., Rosenthal, E., Delaunay, P., Allieri-Rosenthal, E., Gratecos, N. & Cassuto, J.P. (2004) Visceral leishmaniasis: a new opportunistic infection in hematopoietic stem-cell-transplanted patients. Bone Marrow Transplantation, 33, 667668.