Isolated Gastrointestinal Graft versus Host Disease in a Patient of Multiple Myeloma after Autologous Hematopoietic Stem Cell Transplantation

Special Article - Hematopoietic Stem Cell Transplantation

Ann Hematol Oncol. 2017; 4(4): 1146.

Isolated Gastrointestinal Graft versus Host Disease in a Patient of Multiple Myeloma after Autologous Hematopoietic Stem Cell Transplantation

Garg A, Yadav S and Nityanand S*

Department of Hematology, Sanjay Gandhi Post Graduate Institute of Medical Sciences, India

*Corresponding author: Nityanand S, Department of Hematology, Sanjay Gandhi Post Graduate Institute of Medical Sciences, Rae Bareli Road, Lucknow 226014, India

Received: February 28, 2017; Accepted: March 14, 2017; Published: March 31, 2017

Abstract

Acute graft versus host disease (GVHD) occurs in 50-70% of patients undergoing allogeneic Hematopoietic Stem Cell Transplantation (HSCT) and is a major cause of post transplantation morbidity and mortality. A syndrome similar to acute GVHD has been reported after autologous HSCT, and has been termed autologous GVHD (auto GVHD). We report a case of multiple myeloma who developed gastrointestinal GVHD, following an autologous HSCT. During the course of the transplant, patient developed severe diarrhoea. Repeated stool examinations showed no pus cells/RBCs, no ova/cyst, no opportunistic pathogens, giardia antigen was negative, and bacterial and fungal cultures were negative. The PCR for CMV was negative; serology for EBV and hepatitis A, E, B and C viruses was negative. The Clostridium difficile toxin assay was negative. LFTs were normal. Despite administration of systemic antimicrobials, anti-motility drugs, anti-secretory drugs and probiotics, the diarrhoea was persistent. The rectal biopsy showed features of GVHD, and was negative for CMV, fungi and acid fast bacilli. The patient was started on methylprednisolone @ 2 mg/kg/day in two divided doses. There was a dramatic improvement in the nausea and diarrhoea and the anti-motility and anti-secretory agents could be stopped. Isolated GI GVHD is rare but should be considered in the differential diagnosis of severe unexplained diarrhoea following auto HSCT and appropriate investigations including endoscopy and possibly mucosal biopsy should be undertaken to document the diagnosis and initiate early therapy with steroids.

Keywords: Myeloma; GVHD; Transplant

Abbreviations

GVHD: Graft versus Host Disease; HSCT: Haematopoeitic Stem Cell Transplant; GI: Gastro-intestinal; MM: Multiple Myeloma

Introduction

Acute graft versus host disease (GVHD) occurs in 50-70% of patients undergoing allogeneic Hematopoietic Stem Cell Transplantation (HSCT) and is a major cause of post transplantation morbidity and mortality [1]. A syndrome similar to acute GVHD has been reported after autologous HSCT, and has been termed as autologous GVHD (auto GVHD) [2]. We report a case of multiple myeloma who developed isolated gastrointestinal (GI) GVHD, following an autologous HSCT.

Case Presentation

A 60 year old gentleman with IgG-lambda multiple myeloma was diagnosed at our centre in December 2012. He was treated with Thalidomide and dexamethasone. After completion of 6 cycles, the disease was in complete remission, and he was taken up for an autologous HSCT. Stem cell mobilization was done using cyclophosphamide (2 g/m2 x 2 days) and Granulocyte colony stimulating factor. Harvesting was done on day 11. The conditioning regimen used was Melphalan (200 mg/m2). During the conditioning, he developed neutropenia for which supportive measures were given.

Irradiated blood products were given for transfusions.

The patient engrafted successfully on day +14. On day +16 post transplant he developed nausea, 6-7 episodes of vomiting and diarrhoea. The frequency of diarrhoea ranged from 14 to 21 times/ day. The stools were watery, non mucoid with no blood and with an average volume of 200 ml/stool. The possibilities considered were infective diarrhoea, melphalan-induced diaarhoea or antibiotic associated colitis. There was no remarkable fever and no skin rash. Blood cultures were sterile. Repeated stool examinations showed no pus cells/RBCs, no ova/cyst, no opportunistic pathogens and negativity for giardia antigen. Repeatedly the bacterial and fungal cultures of the stool were negative for pathogenic organisms. The PCR for Cytomegalovirus was negative; as was the serology for Epstein Barr Virus and hepatitis A, E, B, C viruses and Clostridium difficile toxin assay. Liver function tests were normal. Despite administration of systemic antimicrobials, anti-motility drugs, anti-secretory drugs and probiotics, the diarrhoea was persistent. Hence a proctosigmoidoscopy was done on day +19 and a rectal biopsy was taken. The rectal biopsy showed moderate distortion of crypt architecture with crypt shortening, occasional fibro-muscular strands within the inter-crypt space and lamina propria showed minimal mononuclear cells (Figure 1). Staining for CMV, fungi and acid fast bacilli was negative. The patient was started on methylprednisolone @ 2 mg/ kg/day in two divided doses, following which there was a dramatic improvement in the nausea and diarrhoea and the anti-motility and anti-secretory agents could be stopped. The methylprednisolone was later changed to oral prednisolone and the patient was discharged on day +45. At the time of discharge the stool frequency had decreased to three times/day. The bowel habits returned to normal in 2-3 weeks after discharge and prednisolone was gradually tapered and stopped over a period of 3 months. The patient has been in follow-up for past three years, with no recurrence of the GI symptoms and the disease continues to be in remission.

Citation:Garg A, Yadav S and Nityanand S. Isolated Gastrointestinal Graft versus Host Disease in a Patient of Multiple Myeloma after Autologous Hematopoietic Stem Cell Transplantation. Ann Hematol Oncol. 2017; 4(4): 1146. ISSN:2375-7965