Immunophenotypic diversity and prognosis of adult T-cell leukemia/lymphoma

17565 Background: Adult T-cell leukaemia/lymphoma (ATLL) is an aggressive disease associated with human T-cell lymphotropic virus type-I (HTLV-I) with heterogeneous clinical presentation and outcomes, described in Southern Japan, Europe, Caribbean and previously on Pacific coast of South America including Peru (EHA 2001, abst. 304). Shimoyama’s ATLL classification (BHJ 1991:79), includes four types: acute, lymphomatous, chronic and smouldering; recently a new clinical cutaneous type had been described (BJD 2005:152). Methods: We described our experienced previously (ASH 2005, abst. 4797). Herein we analyzed immunophenotypically our ATLL patient population by flow cytometry looking for aberrant phenotypes and their correlation with overall survival. The statistical method was descriptive and survival was calculated using the Kaplan-Meier method. Results: From July 1997 to March 2005 our registry had 69 cases, 37 had flow pre-treatment: acute type (n = 31) and lymphomatous (n = 6). Over our 37 flow done we were able to analysis only 33. The incidence of the typical (CD4+/CD8-) phenotype, the double-negative (CD4-/CD8-), the double-positive (CD4+/CD8+), and the CD8 positive (CD4-/CD8+) phenotypes was 58%, 12%, 15%, and 12% respectively. The median overall survival (OS) for the 33 patients was 4.1 months (range: 0.5–46.1). The patients with typical phenotypes had a median OS of 4.1 months better than the patients with the double-negative phenotype whom median OS was 2.0 (range: 1.5–9.7) but not significant. Median OS in the double positive and the CD4-/CD8+ phenotype population were 15.2 and 4.8 months respectively with no significance Conclusions: ATLL has a diversity of immunophenotype, our data suggest that there is not any correlation with survival, major accrual will gave us a final conclusion. No significant financial relationships to disclose.

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Clinical Outcomes in Adult T Leukemia/Lymphoma: Report of 55 Cases from Peru.

Blood ◽

10.1182/blood.v106.11.4797.4797 ◽

2005 ◽

Vol 106 (11) ◽

pp. 4797-4797

Author(s):

Brady E. Beltrán-Gárate ◽

Antonio A. Carrasco-Yalan ◽

Olga M. Lopéz-Odría ◽

Luis Riva-Gonzales ◽

Hugo Ríos ◽

...

Keyword(s):

T Cell ◽

Complete Response ◽

Cell Leukaemia ◽

Type I ◽

Acute Type ◽

Stratify Analysis ◽

Human T Cell ◽

Blood Smears ◽

Beta 2 ◽

Beta 2 Microglobulin

Abstract Adult T -cell leukaemia/lymphoma (ATL) is an aggressive disease associated with human T-cell lymphotropic virus type-I (HTLV-I) with heterogeneous clinical presentation and outcomes, described in Southern Japan, Europe, Caribbean and previously on Pacific coast of South America including Peru (EHA 2001, abst. 304). Shimoyama’s ATL classification (BHJ1991:79) includes four types: acute, lymphomatous, chronic and smoldering; recently a new clinical type cutaneous had been described (BJD2005:152). Herein we show our experience in ATL in our institution between October 1997 and May 2005 All our 55 cases shown positivity to HTLV-I Western Blot test; immune-histopathology, blood smears and flow cytometry showed mature T-cell lymphocyte. Median age at diagnosis 61 years old (range 23–84), female/male ratio: 1.2. Thirty-one (56%) patients had ECOG status performance at diagnosis ≥ 2. Clinical types: acute (n=26), lymphomatous (n=22), smouldering (n=2), cutaneous (n=5) with no chronic type observed. Median haemoglobin diagnosis was 12.1 g/dl (range 6.9–17), median albumin was 3.2 g/dl (range 1.8 – 4.9), median beta-2 microglobulin was 4.6 g/dl (range 1.5 – 16.9), median globulin was 2.7 g/dl (range 1.5 – 8.2) and DHL was 796 UI/ml (range 331 – 13000). Twenty-five per cent (9/36) debuted with hypercalemia (acute type=7, lymphomatous=2). Acute ATL showed median leukocytes of 48,900 cell/mm3 (range 6830–259,000). IPI risk score was: low (n=6), low intermediate (n=7), high intermediate (n=16) and high (n=27). Treatment for acute ATL was based on acute leukaemia and lymphoma regimens without any response but one, interestingly this patient was treated with Fludarabine 25 mg/mt2 day 1–5 each 28 day for 6 cycles and got complete remission. Twenty-one over 24 lymphomatous ATL type were evaluable for treatment response: overall response 38% (9/24) with 26% complete response. Smouldering and cutaneous ATL types received mainly topic treatments. Stratify analysis for IPI, DHL, beta-2 microglobulin, globulin and albumin for acute and non-acute ATL did not show any statistic difference. Median overall survival was: acute type (2.0 months DE 0.2), lymphomatous type (10.2 months DE 3.6), smouldering type (17.2 months) and cutaneous type (36.2 months DE 19.5) (Log Rank 30,76 p=0.0) ATL persist is a poor prognostic peripheral T-lymphocytic malignancy with bad clinical and therapeutically outcomes mainly in the acute type. Cutaneous type seems to be less aggressive. Figure Figure

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Addition of Anti-Viral Therapy to Chemotherapy Improves Overall Survival In Acute and Lymphomatous Adult T-Cell Leukaemia/Lymphoma (ATLL)

Blood ◽

10.1182/blood.v116.21.3961.3961 ◽

2010 ◽

Vol 116 (21) ◽

pp. 3961-3961 ◽

Cited By ~ 2

Author(s):

Andrew Hodson ◽

Silvia Montoto ◽

Naheed Mir ◽

Antonio Pagliuca ◽

Kate Cwynarski ◽

...

Keyword(s):

Overall Survival ◽

T Cell ◽

Meta Analysis ◽

Biological Data ◽

Cell Leukaemia ◽

Interferon Α ◽

Acute Type ◽

Line Treatment ◽

First Line ◽

Human T Cell

Abstract Abstract 3961 Introduction: 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). Aims: To report the clinico-pathologic characteristics, treatment and outcome of patients diagnosed with ATLL in England from 1999 to 2009. Methods: 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. Results: 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. Conclusions: 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. Disclosures: Ardeshna: Roche: Funding data manager, Honoraria, Membership on an entity's Board of Directors or advisory committees.

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