Severe acute axonal neuropathy following treatment with arsenic trioxide for acute promyelocytic leukemia: a case report

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Marcus Kuhn
Mithia Nabergoj
Kety Sammartin
Fabrizio Vianello *
(*) Corresponding Author:
Fabrizio Vianello | fabrizio.vianello@unipd.it

Abstract

Peripheral neuropathy is a common complication of arsenic toxicity. Symptoms are usually mild and reversible following discontinuation of treatment. A more severe chronic sensorimotor polyneuropathy characterized by distal axonal-loss neuropathy can be seen in chronic arsenic exposure. The clinical course of arsenic neurotoxicity in patients with coexistence of thiamine deficiency is only anecdotally known but this association may potentially lead to severe consequences.

We describe a case of acute irreversible axonal neuropathy in a patient with hidden thiamine deficiency who was treated with a short course of arsenic trioxide for acute promyelocytic leukemia. Thiamine replacement therapy and arsenic trioxide discontinuation were not followed by neurological recovery and severe polyneuropathy persisted at 12-month follow-up.

Thiamine plasma levels should be measured in patients who are candidate to arsenic trioxide therapy. Prophylactic administration of vitamin B1 may be advisable. The appearance of polyneuropathy signs early during the administration of arsenic trioxide should prompt electrodiagnostic testing to rule out a pattern of axonal neuropathy which would need immediate discontinuation of arsenic trioxide.  


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Author Biographies

Marcus Kuhn, University of Padova

Resident Physician in Allergology and Clinical Immunology Haematology and Clinical Immunology Unit

Mithia Nabergoj, University of Padova

Resident Physician in Hematology Haematology and Clinical Immunology Unit

Kety Sammartin, University of Padova

Resident Physician in Hematology Haematology and Clinical Immunology Unit

Fabrizio Vianello, University of Padova

Assistant Professor of Medciine, Hematology and Clinical Immunology Unit, Department of Medicine

References

1. Soignet SL, Frankel SR, Douer D, Tallman MS, Kantarjian H, Calleja E, Stone RM, Kalaycio M, Scheinberg DA, Steinherz P, Sievers EL, Coutré S, Dahlberg S, Ellison R, Warrell RP Jr.. United States multicenter study of arsenic trioxide in relapsed acute promyelocytic leukemia.
J Clin Oncol 2001;19:3852-60.

2. Niu C1, Yan H, Yu T, Sun HP, Liu JX, Li XS, Wu W, Zhang FQ, Chen Y, Zhou L, Li JM, Zeng XY, Yang RR, Yuan MM, Ren MY, Gu FY, Cao Q, Gu BW, Su XY, Chen GQ, Xiong SM, Zhang TD, Waxman S, Wang ZY, Chen Z, Hu J, Shen ZX, Chen SJ. Studies on treatment of acute promyelocytic leukemia with arsenic trioxide: remission induction, follow-up, and molecular monitoring in 11 newly diagnosed and 47 relapsed acute promyelocytic leukemia patients. Blood 1999; 94:3315–24

3. Soignet SL, Maslak P, Wang ZG, Jhanwar S, Calleja E, Dardashti LJ, Corso D, DeBlasio A, Gabrilove J, Scheinberg DA, Pandolfi PP, Warrell RP Jr.. Complete remission after treatment of acute promyelocytic leukemia with arsenic trioxide. N Engl J Med 1998; 339:1341–48.

4. G.Lazo, H. Kantarjian, E. Estey, D. Thomas, S. O’Brien, J. Cortes Use of Arsenic Trioxide (theTreatment of Patients with Acute Promyelocytic Leukemia. Cancer 2003; 97:2218-24.

5. Raffoux E, Rousselot P, Poupon J, Daniel MT, Cassinat B, Delarue R, Taksin AL, Réa D, Buzyn A, Tibi A, Lebbé G, Cimerman P, Chomienne C, Fermand JP, de Thé H, Degos L, Hermine O, Dombret H.. Combined treatment with arsenic trioxide and all trans-retinoic acid in patients with
relapsed acute promyelocytic leukemia. J Clin Oncol 2003; 21: 2326–34.

6. Shen ZX, Shi ZZ, Fang J, Gu BW, Li JM, Zhu YM, Shi JY, Zheng PZ, Yan H, Liu YF, Chen Y, Shen Y, Wu W, Tang W, Waxman S, De Thé H, Wang ZY, Chen SJ, Chen Z..
All-trans retinoic acid/As2O3 combination yields a high-quality remission and survival in newly diagnosed acute promyelocytic leukemia. Proc Natl Acad Sci U S A 2004;101:5328–35.

7. Shigeno K, Naito K, Sahara N, Kobayashi M, Nakamura S, Fujisawa S, Shinjo K, Takeshita A,Ohno R, Ohnishi K. Arsenic trioxide therapy in relapsed or refractory japanese patients with acute promyelocytic leukemia: updated outcomes of the phase II study and postremission therapies. Int J Hematol 2005; 82:224–9.

8. Mathews V, George B, Lakshmi KM, Viswabandya A, Bajel A, Balasubramanian P, Shaji RV, Srivastava VM, Srivastava A, Chandy M. Single-agent arsenic trioxide in the treatment of newly
diagnosed acute promyelocytic leukemia: durable remissions with minimal toxicity. Blood 2006; 107:2627–32.

9. Estey E, Garcia-Manero G, Ferrajoli A, Faderl S, Verstovsek S, Jones D, Kantarjian H. Use of all-trans retinoic acid plus arsenic trioxide as an alternative to chemotherapy in untreated acute promyelocytic leukemia. Blood 2006; 107: 3469–73.

10. Ghavamzadeh A, Alimoghaddam K, Rostami S, Ghaffari SH, Jahani M, Iravani M, Mousavi SA, Bahar B, Jalili M.. Phase II study of single-agent arsenic trioxide for the front-line therapy of
acute promyelocytic leukemia. J Clin Oncol 2011;29:2753–7.

11. Iland HJ, Bradstock K, Supple SG, Catalano A, Collins M, Hertzberg M, Browett P, Grigg A, Firkin F, Hugman A, Reynolds J, Di Iulio J, Tiley C, Taylor K, Filshie R, Seldon M, Taper J, Szer
J, Moore J, Bashford J, Seymour JF; Australasian Leukaemia and Lymphoma Group. All-trans-retinoic acid, idarubicin, and IV arsenic trioxide as initial therapy in acute promyelocytic leukemia
(APML4). Blood 2012;120:1570-80.

12. Yip SF, Yeung YM, Tsui EY. Severe neurotoxicity following arsenic therapy for acute promyelocytic leukemia: potentiation by thiamine deficiency. Blood 2002;99:3481-2.

13. Koike H, Iijima M, Sugiura M, Mori K, Hattori N, Ito H, Hirayama M, Sobue G. Alcoholic neuropathy is clinicopathologically distinct from thiamine-deficiency neuropathy. Ann Neurol. 2003;54:19-29.

14. Gryzycki S, Kobusowna B: Histophysiological effects of arsenic and its derivatives on the central nervous system, and particularly on the third element of the central nervous system. J
Neuropathol Exp Neurol 1951;10:325-37.

15. Donofrio PD, Wilbourn AJ, Albers JW, Rogers L, Salanga V, Greenberg HS. Acute arsenic intoxication presenting as guillain barre-like syndrome. Muscle & nerve 1987;10:114-20.

16. Nandi D, Patra RC, Swarup D. Effect of cysteine, methionine, ascorbic acid and thiamine on arsenic-induced oxidative stress and biochemical alterations in rats. Toxicology 2005;211:26–35