A 17 year old Saudi male was diagnosed to have Pre-B ALL in March 2002 at King Fahad National Guard Hospital in Riyadh. He presented with fever, mucosal bleeding, generalized external lymphadenopathy, splenomegaly, thrombocytopenia, normal WBC count and Hb level, blasts on the blood film and a heavy infiltration of the bone marrow with blast cells in addition to complex cytogenetic abnormalities. He received an induction course of chemotherapy composed of cyclophosphomide, daunorubicin, vincristine, L-asparaginase, prednisone and intrathecal methotrexate, following which the first complete remission (CR) of his leukemia was achieved. Thereafter, the patient was given consolidation and maintenance courses of chemotherapy till March 2004. In February 2005, he had relapse of his ALL with almost the same clinical and laboratory abnormalities. However, he achieved a second CR following a salvage course of chemotherapy composed of high dose cytosine arabinoside and idarubicin. After identifying a healthy and an HLA-identical sibling donor, the patient was transferred to King Faisal Specialist Hospital and Research Centre (KFSH&RC) in Riyadh for an allogeneic HSCT. On admission to the HSCT unit on 18/4/05, he was asymptomatic and his physical examination revealed no abnormality. Complete blood count (CBC) showed WBC: 3.72 x 109/L, Hb: 136 g/L and PLT: 256 x 109/L. Blood film showed no blast cells and pre-HSCT bone marrow biopsy showed no evidence of leukemia. The patient received a conditioning protocol composed of cyclophosphamide and TBI. He was given acyclovir, trimethoprim-sulphamethoxa-zole (TMP/SMZ) and fluconazole as infection prophylaxis as well as cyclosporine and methotrexate as graft versus host disease (GVHD) prophylaxis. On 25/4/2005, the patient received his allograft without any complications. In the early post-HSCT period, he developed grade I mucositis treated with IV morphine infusion and two febrile neutropenic episodes treated empirically with tazobactampiperacillin, gentamicin and vancomycin. He engrafted his leucocytes on day +20 and his platelets on day +12 HSCT. On day +28 HSCT, the patient developed acute GVHD of the skin, which was treated with IV 6-methylpednisolone then oral prednisone. After controlling the skin GVHD, he was sent home on cyclosporine, zantac and prophylactic antimicrobials in addition to the tapered doses of prednisone.
On day +135 HSCT, the patient was readmitted with an extensive chronic GVHD involving skin, mouth, colon and liver. He presented with fever, abdominal pain and diarrhea for one week and he gave history of taking food from a restaurant. Physical examination revealed an unwell young male with generalized pigmentation, jaundice and lichenoid oral eruptions but no leg edema or external lymphadenopathy. The chest was clear, the cardiovascular and the neurological examinations were normal but examination of the abdomen revealed diffuse tenderness, positive bowel sounds and no hepatosplenomegaly. The CBC showed: WBC: 6.3 x 109/L, Hb: 160 g/L and PLT: 271 x109/L. The renal function tests were normal. The hepatic profile revealed: serum bilirubin: 96 mumol/L, albumin: 35 g/L, ALT: 558 U/L, AST: 209 U/L and alkaline phosphate: 404 U/L. Colonoscopy was done and it showed grade I GVHD of the colon. The patient was kept on bowel rest and he was commenced on: intravenous (IV) fluids, IV methylprednisolone 1mg/kg twice daily, IV zantac 50 mg thrice daily and IV immunoglobulin 0.4 g/kg weekly in addition to prophylactic acyclovir and TMP/SMZ. The stool cultures grew Salmonella species so the patient received IV ceftriaxone 2 grams daily for 10 days. As diarrhea continued, the patient was commenced on: mycophenolate mofetil (MMF) 500 mg twice daily, ursodeoxycholic acid 300 mg orally twice daily, IV omeprazole and octreotide 50 mug IV thrice daily. On day +145 HSCT, he was started on IV ganciclovir: 5 mg/kg twice daily as cytomegalovirus (CMV) antigen test became positive. A repeat colonoscopy showed severe colitis with grade IV colonic GVHD (Fig. 1). Later on, the patient continued to have low grade pyrexia, abdominal pain and diarrhea so he was commenced on total parenteral nutrition and rabbit anti-thymocyte globulin 1.5 mg/kg on alternative days for a total of 3 doses and cyclosporine was replaced by tacrolimus. On day +152 HSCT, the patient was still having positive CMV antigenemia and the previously taken colonic biopsy became positive for CMV (Fig. 1) so IV ganciclovir was replaced by IV foscarnet 60 mg/kg thrice daily. Few days later, the bloody diarrhea and the abdominal pains decreased significantly, then the patient continued to improve clinically. On day +177 HSCT, the patient was having no more diarrhea or abdominal pain, so he was shifted to oral prednisone 1.5 mg/kg/day for 3 days and a maintenance dose of IV foscarnet 100 mg/kg/day. Four days later, the patient was asymptomatic and his physical examination showed hyperpigmentation but no jaundice or abdominal tenderness. The blood counts showed: WBC: 2.02 x 109/L, Hb: 10/g/L and PLT: 73 x 109/L. The renal function tests were all normal. The hepatic profile showed: bilirubin 82 mumol/L, ALT: 100 U/L and AST 31 U/L. The patient was sent home on: foscarnet 500 mg IV once daily for one more week, tacrolimus 5 mg orally twice daily, MMF 1 gram twice daily, prednisone 50 mg/day and ursodeoxycholic acid 150 mg daily. Thereafter, the patient had a regular follow up at the HSCT outpatient clinic and he sustained his clinical and laboratory improvement which allowed gradual tapering of his immunosuppressive therapy.