A 29-year-old man with Philadelphia chromosome-negative B-ALL had been treated in another hospital. He achieved CR after induction chemotherapy and continued consolidation chemotherapy. Although he had been in CR after the third course of consolidation chemotherapy, he had a relapse during the fourth. For reinduction therapy, he was treated with INO (0.8 mg/m2 on day 1, 0.5 mg/m2 on days 8 and 15). The percentage of lymphoblasts after the first course of INO was 15%. However, he finally achieved a second CR (0.1% lymphoblasts) after the second course of INO. He was transferred to our hospital for allogeneic HSCT.
At the time of admission, laboratory tests showed white blood cell count 1.56 x 109/l, blasts 0%, red blood cell count 429 x 1010/l, hemoglobin concentration 13.0 g/dl, and platelet count 53.0 x 109/l. Although the serum level of aspartate transaminase (AST) was slightly increased (34 U/l; normal range, 13-30 U/l), alanine aminotransferase (ALT) (30 U/l; normal range, 10-42 U/l) and total bilirubin (0.81 mg/dl; normal range, 0.40-1.50 mg/dl) were within the normal range. Hepatitis B surface antigen, anti-hepatitis B surface and core antibodies, and anti-hepatitis C virus antibody were negative. Contrast-enhanced computed tomography did not detect any extramedullary lesions. Bone marrow aspiration showed no lymphoblasts in the smear, and flow cytometric analysis detected <1.0% blasts. Minimal residual disease analysis by measuring immunoglobulin heavy chain rearrangement was not performed.
The conditioning regimen for HSCT comprised fludarabine 30 mg/m2/day from days -7 to -5 and total body irradiation (TBI) of 12 Gy delivered in six fractions from days -4 to -2, followed by peripheral blood stem cell transplantation (PBSCT) from a haploidentical sibling donor. He received posttransplant cyclophosphamide (PT-CY) 40 mg/kg on days +3 and +4. Posttransplantation immunosuppression was initiated on day +5 with intravenous tacrolimus (target level, 10-12 ng/ml) and oral mycophenolate mofetil (MMF; 15 mg/kg body weight twice daily) for graft-versus-host disease (GVHD) prophylaxis. The total infused dose of CD34-positive cells was 4.64 x 106 cells/kg body weight. Ursodeoxycholic acid (200 mg/body, thrice daily) for veno-occlusive disease (VOD)/SOS prevention was initiated on day -7.
The disease status before initiation of the conditioning regimen was CR. However, swelling of the left submandibular mass appeared on day -2. Bone marrow examination on day -1 showed blast-like cells, approximately 7% of total nuclear cells. A needle biopsy of the mass lesion on day 0 showed that the lymph node was infiltrated by lymphoblasts later. He received PBSCT on day 0, 39 days after the last INO administration.
The left submandibular mass gradually improved and disappeared around day +7. On day +17, we performed bone marrow examination because his peripheral blood did not show any recovery of neutrophils. The bone marrow examination showed a hypocellular marrow with no blasts; however, there were 39% macrophages, suggesting hemophagocytosis. On days +17 and +18, we administered dexamethasone palmitate 5 mg/day, and neutrophil engraftment was finally observed on day +22. Administration of MMF was gradually decreased from day +30 and terminated after 7 days. Bone marrow examination on day +31 showed normocellular marrow without lymphoblasts, suggesting CR. Fluorescence in situ hybridization of the bone marrow fluid indicated complete donor chimerism. On day + 34, 18F-fluorodeoxyglucose positron emission tomography/computed tomography found no extramedullary infiltration of ALL. He developed a skin rash and was diagnosed with acute GVHD on day +35; however, no other acute GVHD features were observed in the liver and intestine. Grade I skin acute GVHD was improved by treatment with topical steroids. He was discharged on day +52. During the hospitalization period, we did not observe any laboratory results or signs suggesting SOS. Fig. 1 shows the clinical course of the patient. Unfortunately, his ALL recurred in the bone marrow on day +89, and he died on day +158.