Abstract
Abstract 3961
Adult T-cell leukaemia/lymphoma (ATLL) is an aggressive T-cell malignancy associated with human T-cell lymphotropic virus type 1 (HTLV-1) infection. Outcomes with chemotherapy alone are poor and drug resistance is common. Projected 2 and 4 year survival rates were 16.7% and 5% for acute ATLL and 21.3% and 5.7% for lymphomatous ATLL have been reported (Shimoyama et al, 1991). Therapy with Zidovudine (ZDV) and Interferon-α (IFN) has been associated with improved response rates and overall survival in small studies. A recent meta-analysis has demonstrated the efficacy of ZDV/IFN over chemotherapy in acute and chronic ATLL but not in lymphomatous ATLL (Bazarbachi et al, 2010).
To report the clinico-pathologic characteristics, treatment and outcome of patients diagnosed with ATLL in England from 1999 to 2009.
84 patients with ATLL were identified and their records individually reviewed. Epidemiological, clinical and biological data were collected including ATLL subtype, treatment, response and overall survival. Diagnosis was made on the basis of tissue involvement with a characteristic immunophenotype and confirmation of HTLV1 infection. Cases were classified according to Shimoyama.
ATLL was more frequent in females (1.5F:1M). Ethnic origin was Afro-caribbean (77%) or African (18%) in the majority. Median age 54.6 years.29 cases were acute, 44 lymphomatous, 9 chronic and 2 smouldering (cutaneous) ATLL. Presenting characteristics are tabulated. Corrected calcium (p=0.036) and lactate dehydrogenase (p=0.028) were significantly higher in acute v lymphomatous ATLL. Overall median survival (MS) was 7.5 months for acute, 10.2 months for lymphomatous, 47.6 months for chronic and 32.4 months for cutaneous ATLL. First line treatment for aggressive (acute or lymphomatous) ATLL was chemotherapy +/− AZT/IFN in all patients except 2 with acute ATLL not fit for chemotherapy. MS was 12.2 months in 26 patients receiving first line chemotherapy with ZDV/IFN compared to 4.4 months for 31 patients treated with chemotherapy alone (p=0.002). MS rates were best in patients who, having initially responded to chemotherapy, were treated with ZDV/IFN at relapse (19.6 months). By subtype, in acute ATLL, MS was 10.1 months in 20 patients receiving ZDV/IFN at any time (1st line or relapse) and 4.1 months in 9 patients who never received ZDV/IFN (p=0.004). Patients who received ZDV/IFN at any time had 19% and 10% 2 and 4 year overall survival (OS) respectively as compared to 0% 2 and 4 year OS in the absence of any ZDV/IFN. In lymphomatous ATLL, MS was 13.2 months in 22 patients receiving ZDV/IFN at any time and 5.5 months in 22 patients who never received ZDV/IFN (p=0.001). Patients who received ZDV/IFN at any time had 38% and 23% 2 and 4 year OS respectively compared to 0% 2 and 4 year OS in the absence of any ZDV/IFN. In the chronic ATLL group, 2 year OS was 100% but fell to 40% at 4 years after the development of acute ATLL in 3/9 cases.
| . | Normal range . | Acute Median (range) . | Lymphoma Median (range) . | Chronic Median (range) . |
|---|---|---|---|---|
| Age (years) | – | 54.6 (37.1–77.4) | 62.2 (22.0–85.3) | 39.7 (31.3–65.3) |
| Lymphocyte count (×109/L) | 1.3–3.7 | 14.3 (4.3–147.0) | 2.0 (0.5–3.9) | 12.0 (5.2–49.9) |
| Corrected Ca++ >ULN (%) | – | 62% | 28% | 0 |
| LDH>2 × ULN (%) | – | 82% | 61% | 0 |
| CNS disease | – | 17% | 18% | – |
| ECOG PS≥2 (%) | – | 25% | 38% | 0 |
| . | Normal range . | Acute Median (range) . | Lymphoma Median (range) . | Chronic Median (range) . |
|---|---|---|---|---|
| Age (years) | – | 54.6 (37.1–77.4) | 62.2 (22.0–85.3) | 39.7 (31.3–65.3) |
| Lymphocyte count (×109/L) | 1.3–3.7 | 14.3 (4.3–147.0) | 2.0 (0.5–3.9) | 12.0 (5.2–49.9) |
| Corrected Ca++ >ULN (%) | – | 62% | 28% | 0 |
| LDH>2 × ULN (%) | – | 82% | 61% | 0 |
| CNS disease | – | 17% | 18% | – |
| ECOG PS≥2 (%) | – | 25% | 38% | 0 |
Our results point to the benefit of treatment with ZDV/IFN at some stage, given the failure of any patient to survive 2 years in the absence of this therapy. In the recent meta-analysis insufficient patient numbers with lymphoma were treated with adjunctive ZDV/IFN therapy to demonstrate any benefit, whilst first line therapy with ZDV/IFN alone was ineffective. However, we have documented significant clinical benefit from the addition of ZDV/IFN to chemotherapy in lymphomatous ATLL. Together these two studies suggest the following treatment approach to improve outcome in aggressive ATLL: Acute type– 1st line treatment with AZT/IFN alone. Lymphomatous type - 1st line treatment with chemotherapy and early addition of ZDV/IFN. This is a major step forward in ATLL therapy, but it is important to recognise that some patients will fail therapy and overall survival remains poor.
Ardeshna:Roche: Funding data manager, Honoraria, Membership on an entity's Board of Directors or advisory committees.
Author notes
Asterisk with author names denotes non-ASH members.
