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Treatment of T-Cell Anaplastic Large Cell Lymphoma Relapsing after Autologous Stem Cell Transplant with Denileukin Difitox

Treatment of T-Cell Anaplastic Large Cell Lymphoma Relapsing after Autologous Stem Cell Transplant with Denileukin Difitox

Blood 100(11): Abstract No 4772, November 16

ALCL, T/null cell type is the second most common T-cell lymphoma and represents approximately 2% of all adult Non-Hodgkin's lymphoma. The neoplastic cells express CD30 (Ki-1) and either T-cell or no lineage specific antigens. ALCL often expresses CD25 (IL-2 receptor). While most cases of cutaneous ALCL are anaplastic lymphoma kinase (ALK) negative, the majority of systemic cases are positive for ALK. In general, the prognosis for systemic ALK negative ALCL in adults is poor and therapy is not well defined. Ontak is a targeted, cytotoxic fusion protein consisting of diphtheria toxin bound to human IL-2. We report two patients with primary systemic T cell ALCL (ALK negative, CD25 positive) treated with Ontak at relapse after ASCT to demonstrate its safety and lack of organ toxicity. Case 1: A 64 year-old man presented with stage I-A ALCL involving left cervical nodes. Based on normal LDH and PS 0, he had low age-adjusted IPI (aaIPI). CR was achieved with 3 cycles of CHOP and local RT. After 12 months, he relapsed in small bowel and mesenteric nodes. With 2 cycles of salvage DHAC (cytarabine, dexamethasone and carboplatin), he had no evidence of disease and underwent ASCT using cyclophosphamide (CPA), thiotepa and etoposide. He had recurrence in abdominal lymph nodes 2 months post-transplant. He received one cycle of Ontak (5 doses at 9 mcg/kg/dose every other day) and tolerated the infusion well without developing any hematologic or organ toxicity. No response was noted and the patient went on to receive multiple other agents but died of recurrence 11 months post-transplant. Case 2: A 53 year-old man presented with stage III-B ALCL involving cervical, mediastinal and paraaortic nodes and the spleen. Based on normal LDH and PS 1, the aaIPI was low intermediate . After 4 cycles of CHOP, splenomegaly persisted. He underwent splenectomy confirming residual disease. After one cycle of ICE (ifosfamide, carboplatin and etoposide), CT and PET scans demonstrated CR. He underwent ASCT using CPA, etoposide and TBI. He had biopsy-proven recurrence in the liver 3 months post-transplant after presenting with a ten-fold increase in hepatic transaminases and total bilirubin of 11.8 mg/dl. One cycle of Ontak (5 doses at 9 mcg/kg/dose every other day) was given. It was well tolerated and the liver function tests improved remarkably (bilirubin decreased to 1.5 mg/dl and transaminase to two-fold above the normal) after four doses. He next received cyclophosphamide while awaiting search results for an unrelated stem cell donor but died within 3 months from progressive disease before undergoing allogeneic transplant. A search of the literature revealed only one report of Ontak administration pre-ASCT and two reports of its use in peripheral T-cell lymphomas. This is the first report of its use in the post-ASCT setting. The results demonstrate that administration of Ontak in this setting did not produce any infusion-related toxicity or any hematologic or organ toxicity. It also demonstrates that Ontak produced an objective clinical response in a patient with markedly abnormal liver function, a situation where other cytotoxic drugs would be prohibitive. These data provide a rationale for incorporation of Ontak into an early aggressive treatment plan for relapsed ALK negative ALCL to further evaluate its efficacy.

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Accession: 035980623

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