Case Report Strongyloidiasis Pre and Post Autologous Peripheral Blood Stem Cell Transplantation
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Bone Marrow Transplantation (2003) 32, 115–117 & 2003 Nature Publishing Group All rights reserved 0268-3369/03 $25.00 www.nature.com/bmt Case report Strongyloidiasis pre and post autologous peripheral blood stem cell transplantation H Orlent1, C Crawley2, K Cwynarski2, R Dina3 and J Apperley2 1Department of Haematology, Academisch Ziekenhuis Rotterdam, Dijkzigt, Netherlands; 2Department of Haematology, Hammersmith Hospital, London, UK; and 3Department of Cytopathology, Hammersmith Hospital, London, UK Summary: Case 1 Hyperinfection with strongyloides stercolis occurs in the A 67- year-old Guyanian man who had been resident in the setting of chronic strongyloides infection in conjunction UK for the previous 36 years presented with IgG kappa with immune suppression. Although malnutrition remains myeloma in February 1998.He was treated to a partial the major secondary cause worldwide in the developed response (PR) with three courses of VAD chemotherapy world, iatrogenic immue suppression is an important (infusional vincristine and doxorubicin with dexametha- precipitant. Autologous stem cell transplantation recipi- sone 40 mg D 1–5).Peripheral blood stem cells (PBSC) were ents are significantly immunocompromised albeit tem- subsequently mobilised with cyclophosphamide 1.5 g/m2 porarily. Despite the increasing use of haemopoetic stem and G-CSF.Prior to autograft in July 1998, the patient cell transplantation, hyperinfection with strongyloides has complained of epigastric discomfort for the previous 6 rarely been reported. We describe two cases of patients weeks.There were no associated gastrointestinal symp- transplanted with chronic strongyloidiasis. In one case toms.An eosinophilia of 2.74  109/l was noted.His travel eradication therapy was given prior to the transplant history was unremarkable, having last visited Guyana in which was uncomplicated. In the second case strongyloi- 1976.Past medical history included falciparum malaria and diasis was diagnosed post transplant which was compli- duodenal ulcer treated with a proton pump inhibitor in cated by infection and respiratory compromise. Fatal 1995.Gastroscopy demonstrated a moderate erosive hyperinfection subsequently developed after corticosteroid duodenitis but no parasites were seen on the duodenal therapy was started for a disease progression in the CNS. aspirate.Strongyloides serology was strongly positive and Bone Marrow Transplantation (2003) 32, 115–117. Strongyloides stercoralis larvae were identified on direct doi:10.1038/sj.bmt.1704104 microscopy of stool specimens using an ether concentration Keywords: strongyloidiasis; haematopoietic stem cell technique.The patient was treated with albendazole 400 mg transplantation; myeloma; lymphoma b.i.d. for 3 days and ivermectin 200 mg/kg daily for 2 days. Since complete eradication of Strongyloides infection is difficult to prove, the treatment was repeated 1 week later. All subsequent stool examinations were negative.He had Human strongyloidiasis is endemic throughout much of an uneventful autologous transplant conditioned with high- Africa, Asia, South America and the South Eastern United dose melphalan (110 g/m2) and supported with 3.3  106 States.Primary infection involves penetration of the skin CD34+ cells.Neutrophil engraftment ( 40.5  10.9/l) by soil-dwelling infectious filariform larvae.The ability of occurred on day 16.The patient was discharged from the excreted rhabditiform larvae to develop directly to the hospital in good condition on day 36 post-PBSCT.At filariform without the need for an intermediate host follow-up 36 months later, he has stable refractory allows the development of an auto-infection cycle and myeloma with a current paraproteinaemia of 49 g/l. hence the capacity to maintain a lifelong infestation.This distinguishes Strongyloides from the other intestinal nema- todes.We present here two patients with chronic strongy- loidiasis who underwent autologous bone marrow Case 2 transplantation, one of whom subsequently developed fatal hyperinfection. A 57-year-old man with a prior history of pulmonary tuberculosis presented in 1983 in India with a pathological fracture of his right humerus due to a diffuse large B-cell lymphoma.He received bleomycin, steroid and radio- therapy to a complete response (CR).In 1984, he moved to London.He subsequently remained well until 1996 when he Correspondence: Dr C Crawley, Clinical Haematology, Box 234 Addenbrookes Hospital, Cambridge CB2 2QQ, UK represented with a biopsy-proven recurrent diffuse large E-mail: [email protected] B-cell lymphoma in a cervical lymph node.Bone marrow Received 4 July 2002; accepted 5 September 2002 examination at that time revealed evidence of an underlying Strongyloidiasis and PBSCT H Orlent et al 116 develop directly into the infective filariform larvae allows an auto-infective cycle to become established and the potential for lifelong infection.Many human infections are asymptomatic.The commonest clinical manifestations of chronic disease are abdominal discomfort, often epigastric, and diarrhoea. Strongyloides hyperinfection occurs in the setting of immune suppression.2–5 The secondary infection due to the failure of intestinal mucosal integrity is a serious complication.In addition to the direct consequences of massive larval migration in tissues, penetration of larvae through the gut provides a portal of entry for Gram- negative organisms and this secondary infection is a major cause of death. The widespread use of immunosuppressive drugs and the chronicity of strongyloidiasis makes hyperinfection a clinically important problem in nonendemic countries. However, all immunocompromised states do not seem to Figure 1 Strongyloides stercoralis in the bronchoalveolar lavage.Bron- carry equal risk.It is notable that despite the overlap in chial lavage (Papanicolau  400).The larva is surrounded by red blood cells and haemosiderin-laden macrophages. endemic regions for both HIV and strongyloidiasis, the incidence of infection is not increased above that of the non-HIV-infected population.Furthermore, hyperinfection has been reported in association with HIV infection on only indolent lymphoma.He received six cycles of CHOP a handful of occasions.6 chemotherapy (cyclophosphamide, doxorubicin, vincristine There are no data on confirmed strongyloidiasis in the and prednisolone) with prophylactic intrathecal methotrex- setting of bone marrow transplantation and little data post ate to a CR.A third recurrence in 1999 was treated with solid organ transplants.Renal allografts have been three cycles of dexamethasone, cytarabine and cisplatin reported to precipitate hyperinfection although the major- (DHAP) to a PR.After mobilisation of PBSC with ity are prior to 1990 and the immunosuppression in all etoposide, high-dose therapy with autologous stem cell cases was steroid based.4 There are no reports of clinical rescue was undertaken in July 1999.The conditioning strongyloidiasis in patients while immunosuppressed with regimen included lomustine, cytarabine, cyclophosphamide cyclosporin, although there is one case where auto infection and etoposide.Persistent fever and progressive respiratory occurred in a patient receiving tacrolimus7 and one case deterioration complicated his post transplant course.He where hyperinfection occurred shortly after discontinuing required intubation and assisted ventilation for a total of 13 cyclosporin.8 Relevant to this is the observation that days.On day 19 post transplant, a Gram-positive rod was cyclosporin has antihelminth activity.9,10 We present here isolated which was subsequently identified as an atypical two patients who underwent autologous transplantation mycobacterium (Mycobacterium chelonae).His third remis- who had had chronic strongyloidiasis throughout their sion lasted until July 2000 when he had radiotherapy for a initial chemotherapy, which in both cases included corti- parotid relapse.In November 2000, he represented with a costeroid.In the first case, Strongyloides was eradicated right parietal mass with substantial mass effect.The clinical prior to the transplant and the patient had an uneventful diagnosis of recurrent lymphoma was made and dexa- transplant course.In the second case, the diagnosis was methasone was started.He went on to receive cranial missed as the patient did not have an elevated eosinophil radiotherapy.As the steroid dose was being reduced, he count (probably due to prior corticosteroid) and was became unwell with rising inflammatory markers but no asymptomatic.Although Strongyloides was not isolated, it fever.Despite broad-spectrum antibiotics (including ther- is possible that it contributed to the severe infective apy for Pneumocystis) his chest radiograph deteriorated complications.Subsequently, steroid alone was sufficient and he developed a cough and hypoxaemia. S. stercoralis to allow fatal Strongyloides hyperinfection to develop. was identified on bronchoalveolar lavage (Figure 1) and Steroid induced eosinopenia may be important.Eosino- ivermectin and albendazole were added.Although blood phils are known to be an important component of the cultures were subsequently sterile, and despite the sub- immune response to Strongyloides infection.Activated sequent addition of antifungal antibiotics his condition eosinophils can undoubtedly kill helminthic parasites in deteriorated, with clinical evidence of infection, and he died vitro and IL5 knockout CB57BL/6 mice are more 44 days after the initiation of the steroids.An autopsy was susceptible to primary Strongyloides