Diarrhea after autologous stem cell transplantation in low-middle income countries: is Clostridium difficile the most prevalent infectious etiology?^☆

Diarrhea is a major cause of morbidity during high-dose chemotherapy followed by autologous stem cell transplantation (ASCT). It occurs in almost half of recipients of ASCT and generally, it is attributed to the effects of high-dose chemotherapy on the gastrointestinal mucosa and the effects of broad-spectrum antibiotic regimens for the prophylaxis and treatment of neutropenia. However, other etiologies might be considered, such as viral, bacterial and parasitic infections.^1,2

Despite being the most common etiology of diarrhea after ASCT, the conditioning regime is seldom implicated in severe complications, with some exceptions. Cytarabine-containing regimens, high-dose melphalan (≥200 mg/m²), and regimens containing multiple alkylating agents may cause more severe diarrhea.³

Conversely, infectious causes of diarrhea are less prevalent than damage from conditioning therapy. Clostridium difficile is considered the leading cause of infectious diarrhea among hospitalized patients and is a major concern in immunosuppressed individuals.⁴ Viruses such as cytomegalovirus (CMV) and some serotypes of adenovirus might also be implicated in diarrhea after ASCT, but rarely cause life-threatening complications. Diarrhea secondary to intestinal parasite infection, such as Cryptosporidium, Giardia lamblia, Entamoeba histolytica and helminths, is rare among patients who come to transplant without diarrhea.^5,6Strongyloides infection and non-tuberculous mycobacterial have also been described after ASCT in patients from endemic areas.²

In this issue of Hematology, Transfusion and Cell Therapy, Castro et al. investigated the role of enteric pathogens in 47 recipients of ASCT between May 2011 and May 2013.⁷ Thirty-nine recipients (83%) met the criteria for the diagnosis of diarrhea. Among them, conditioning regime toxicity was the most prevalent cause (35%). Interesting, a high prevalence of infectious etiology was identified. Through an investigational platform based on parasitological stool examination, stool cultures and the identification of A and B C. difficile toxins, 30% of the recipients had an infectious cause as the etiology with Coccidia being the most common. Unexpectedly, C. difficile presented a low incidence in comparison with currently published data⁴ but, in accordance with the frequency and microbiological causes of diarrhea in low-middle income countries.⁸

These results revealed some potential different etiologies of infectious diarrhea in Brazil. However, due to the low number of patients evaluated from a single center, conclusions should be taken with caution. Nevertheless, these data might justify a multicenter study with the aim to clarify etiologies of diarrhea among Brazilian patients. A careful analysis of the causative agents could lead to more accurate management, early intervention and prevention of severe complications.

• ☆
  See paper by Marcelo Dias de Castro et al. on pages [132–135].

REFERENCES

• ¹
  van Kraaij MG, Dekker AW, Verdonck LF, van Loon AM, Vinje J, Koopmans MP, et al. Infectious gastro-enteritis: an uncommon cause of diarrhoea in adult allogeneic and autologous stem cell transplant recipients. Bone Marrow Transplant. 2000;26(3):299-303.
• ²
  Tuncer HH, Rana N, Milani C, Darko A, Al-Homsi SA. Gastrointestinal and hepatic complications of hematopoietic stem cell transplantation. World J Gastroenterol. 2012;18(16):1851-60.
• ³
  Cox GJ, Matsui SM, Lo RS, Hinds M, Bowden RA, Hackman RC, et al. Etiology and outcome of diarrhea after marrow transplantation: a prospective study. Gastroenterology. 1994;107(5):1398-1407.
• ⁴
  Alonso CD, Dufresne SF, Hanna DB, Labbe AC, Treadway SB, Neofytos D, et al. Clostridium difficile infection after adult autologous stem cell transplantation: a multicenter study of epidemiology and risk factors. Biol Blood Marrow Transplant. 2013;19(10):1502-8.
• ⁵
  Stein A, Voigt W, Jordan K. Chemotherapy-induced diarrhea: pathophysiology, frequency and guideline-based management. Ther Adv Med Oncol. 2010;2(1):51-63.
• ⁶
  Bhat V, Vira H, Khattry N, Toshniwal M. Cryptococcus laurentii diarrhea post hematopoietic stem cell transplant. Transpl Infect Dis. 2017;19(2).
• ⁷
  de Castro MD, Chebli JM, Costa LJ, Alves KR, Atalla A, Hallack Neto AE. Infectious diarrhea in autologous stem cell transplantation: high prevalence of coccidia in a South American center. Hematol Transfus Cell Ther. 2018;40(2):132-5.
• ⁸
  Pala C, Kaynar L, Buyukoglan R, Kurnaz F, Metan G, Yazar S, et al. Diarrhea in peripheral stem cell transplant recipients: a developing country's experience. J Infect Dev Ctries. 2014;8(5):635-41.

Publication Dates

• Publication in this collection
  Apr-Jun 2018