Institution: Pathology and Laboratory Medicine Division, VA Puget Sound Health Care System at Seattle, University of Washington
Session: T Lymphoblastic Leukemia/Lymphoma
HISTORY
A 51-year-old man presented to an outside hospital with history of fatigue and weight loss in Nov. 2011. The diagnosis of Precursor T/NK lymphoblastic leukemia/lymphoma was established (sample #1). The patient initially received 3 cycles of HyperCVAD with alternating HD-MTX-ara-C. After achieving a complete remission in Feb. 2012, the patient was referred to our institution for bone marrow transplant. He received the non-myeloablative HLA-matched transplantation conditioning with fludarabine and TBI in March, 2012. Bone marrow evaluation on day 31 post-transplant showed normal engraftment with 100% donor cells without morphologic and immunophenotypic evidence of residual disease. 3 months later after transplantation (June 8, 2012), the bone marrow showed 5% abnormal blasts with the same immunophenotyping profile as at diagnosis (#2). 4.5 months later (July 24, 2012), he came back in a full relapse with 20% abnormal blasts in the peripheral blood (#3). On Aug 24, 2012, Nelarabine was administered by schedule (days 1, 3, and 5) at 1500 mg/m2/day as a 2-h intravenous infusion. After the first cycle, complete morphologic and immunologic remission was achieved. After the completion of a total of two cycles, the patient was discharged in CR with full hematologic recovery and without any neurologic or other complications. A recent bone marrow (performed on Dec 28, 2012) showed normocellular marrow with mild to moderate interstitial reticulin fibrosis without evidence of residual T/NK ALL (#4).
DETAILS
PB (11/11/2011, #1): WBC 27700/mm3, Hgb 9.7g/dl, Plt 11000/mm3, Blasts 65%. PB (06/08/2012, #2): WBC 4500/mm3, Hgb 10.2g/dl, Plt 180000/mm3, Blasts 0%. PB (07/24/2012, #3): WBC 6000/mm3, Hgb 8.0g/dl, Plt 81000/mm3, Blasts 20% (see Fig. 2A). PB (12/28/2012, #4): WBC 2900/mm3, Hgb 13g/dl, Plt 205000/mm3, Blasts 0%. Bone marrow aspirate smear (#2): The cellular spicules with normal trilineage hematopoiesis and 5% blasts (see Fig. 1A). Bone marrow clot section (#2): 50% cellularity with interstitial infiltration of TdT+CD7+ blasts (see Fig. 1B, C and D). Bone marrow biopsy (#4): 50% cellularity with normal trilineage hematopoiesis, mild to moderate interstitial reticulin fibrosis (see Fig. 2B and C) with no evidence of TdT+CD7+ blasts.
IMMUNOHISTOCHEMISTRY AND FLOW CYTOMETRY
Flow cytometry on samples 1, 2, and 3 demonstrated similar immunophenotype in the blast population, positive for cCD3, CD7, CD33, CD34, CD38, CD56, negative for sCD3, CD2, CD4, CD8, CD14, CD15, CD61, CD64, CD16, CD117, or myeloperoxidase. Immunohistochemical stains were performed on the clot section from #2, and demonstrated the blast population with expression of TdT and CD7. No TdT+CD7+ blasts were detected in the biopsy from #4.
CYTOGENETIC FINDINGS
46, XY, t(4;8)(q21;q24),add(12)(p11.2),add(14)(q11.2)[cp18]/46, XY[2]. Even though the breakpoint at 8q24 raised concern for a MYC translocation, FISH with the MYC probe did not show any evidence of a rearrangement of this locus (#1).
MOLECULAR FINDINGS
T cell receptor gamma gene rearrangement PCR analysis was performed on sample #1, and no monoclonal T cell population was detected.
INTERESTING FEATURES
Despite all improvements of first-line therapy, the outcome of adult T-ALL after relapse is extremely poor. The case demonstrates a patient with relapsed T/NK-ALL after transplantation who achieved complete remission on therapy with a promising new agent nelarabine. The use of nelarabine has been associated with severe neurologic events. In our case, nelarabine was successfully administered without the occurrence of neurologic events or evidence of drug-related toxicity.
PROPOSED DIAGNOSIS
Nelarabine induced complete remission in an adult with relapsed T/NK-lineage acute lymphoblastic leukemia
CONSENSUS DIAGNOSIS
Relapsed T-acute lymphoblastic leukemia, with complete response to nelarabine salvage therapy
| Figure 1. Bone marrow aspirate and clot section from #2 |  |
| Figure 2. Peripheral blood smear from #3(A) and bone marrow biopsy from #4 (B and C) |  |