Prolymphocytic Leukaemia: an Update on Biology and Treatment.

PURPOSE OF REVIEW: This review summarises the recent advances in knowledge regarding the biology and treatment of prolymphocytic leukaemias. RECENT FINDINGS: Both B-PLL and T-PLL are genetically complex, and the molecular landscape of these diseases has been well characterised recently. Diagnostic criteria for T-PLL have been refined with the publication of the first international consensus criteria, whereas the diagnosis of B-PLL has been thrown into question by the most recent WHO classification. Treatment advances in B-PLL have relied heavily on the advances seen in CLL that have then been extrapolated to B-PLL with just a few case reports to support the use of these targeted inhibitors. Despite increased knowledge of the biology of T-PLL and some elegant pre-clinical models to identify potential treatments, unfortunately, no improvements have been made in the treatment of T-PLL. Unmet need is a term oft used for many diseases, but this is particularly true for patients with prolymphocytic leukaemias. Ongoing improvements in our understanding of these diseases will hopefully lead to improved therapies in the future.

HTLV-I infections in Barbados: results of a 20-year follow-up study - abstract

Human T-cell lymphotrophic virus type I(HTLV-1) infection is known to be associated with adult T-cell leukaemia/lymphoma (ATL), tropical spastic paraparesis, polymyositis, arthritis, alveolitis, uveitis, and infective dermatitis. Examination of stored sera from Barbados previously identified 41 HTLV-1 seropositives among 1012 participants in a 1972 survey. We have followed up this cohort: (1) to determine the long-term persistence of antibody, (2) to ascertain the risk of seroconbersion in household contacts, and (3) to identify long-term clinical sequelae of HTLV-1 infection. There were 79 HTLV-1 seronegative household contacts from 1972. Subjects were seen without knowledge of their serostatus and those who could be traced completed a questionnaire, had a clinical examination, serological, skin and stool tests. All 16 of the initially identified HTLV-1 seropositive sujects, whowere studied, remained seropositive and all 22 of the identified seronegative household contacts remained uninfected. Of the 22 household contacts, 10 were children of HTLV-1 seropositive mothers. In conclusion, we have confirmed persistence of HTLV-1 infection over 20 years' follow-up. There was no evidence of household transmission or of occult infection with late antibody expression in this study. Many HLTV-I infections are asymptomatic but we identified HLTV-I-associated clinical disorders in 4 cases: chronic dermatitis (2), hepatosplenomegaly (1), and hepatomegaly alone (1); the latter subject also had smouldering ATL (AU)

Clinical and laboratory features of adult T-cell leukaemia lymphoma in Barbados

We describe the clinical and pathological features of 23 Afro-Caribbean patients with adult T-cell leukaemia/lymphoma admitted to the Queen Elizabeth Hospital, Barbados over a 5 year period. There were 9 males and 14 females, with a median age of 38 years (range 14-84). Twelve had acute leukaemia, 10 lymphoma (including 4 with solitary extra nodal lesions) and 1 smouldering subtype. Two patients had a past history of tropical spastic paraparesis/HTLV I associated myelopathy (TSP/HAM). The prognosis was poor, with only 3 complete responses to chemotherapy (CHOP) lasting from 9 to 36 months. We conclude that ATLL in Barbados is similar to the disease in other Caribbean islands and Japan, except that in Barbados the age of onset is over a decade younger than in Japan.(AU)

Human T-cell lymphotropic virus type 1 infection in Barbados: results of a 20-year follow-up study

Forty-one human T-cell lymphotropic virus I (HTLV-1)-seropositive individuals were identified among 1,012 subjects with stored serum samples from a health and seroepidemiological survey conducted in Barbados in 1972. These 41 subjects plus 79 HTLV-1 seronegative household members were targeted in a follow-up study 20 years later. Sixteen seropositive subjects and 22 seronegative subjects were interviewed, examined, and phlebotomized. There were no changes in HTLV-1 serostatus between the 1972 and follow-up serum samples. Three (19 percent) of the seropositive subjects had HTLV-1 serostatus between the 1972 and follow-up serum samples. Three (19 percent) of the seropositive subjects had HTLV-1-associated disorders: two with dermatitis and one with <

HTLV-I serology in neurological patients at the Queen Elizabeth Hospital, Barbados - abstract

A survey of the spectrum of neurological syndromes encountered in Barbados was carried out to determine the pathogenic role of human T-lymphotropic virus (HTLV-I) infection in affected patients. Since 1989, patients with chronic neurological disorders were either recalled or were selected from new referrals to the neurology clinic at the Queen Elizabeth Hospital, Barbados. With the consent of patients, serum and CSF samples were tested for IgG antibodies to HTLV-I, using an enzyme-linked immunosorbent assay method. Positive results were confirmed by Western Immunoblotting at the CAREC Laboratories, in Trinidad. Only patients native to Barbados and the Eastern Caribbean were included in the survey. Twenty-nine (29) of 170 patients tested were serpositive for HTLV-I antibodies 18(62 percent) of the HTLV-I-positive patients had tropical spastic paraparesis (TSP). Of 21 seropositive patients who also had CFS-positive antibodies status, 16(76 percent) had TSP, 2(9.5 percent) adult T-cell leukaemia/lymphoma (ATLL), and 3 (14 percent) polymyositis, including 2 with an atypical clinical profile. HTLV-I seronegative patients included 12 (8.5 percent) with ataxia, 19(13.5 percent) with a relapsing/remitting sydrome characteristic of multiple sclerosis, 8(5.5 percent) with idiopathic intracranial hypertension and 8(5.5 percent) with stroke. HTLV-I positive associated neurological diseases in Barbados consist primarily of myelopathy (TSP). Some cases present more complex patterns of neurlogical dysfunction, associated with polymyositis. (AU)

Clinical and laboratory features of adult T-cell leukemia lymphoma in Barbados

We describe the clinical and pathological features of 23 Afro-Caribbean patients with adult T-cell leukemia/lymphoma admitted to the Queen Elizabeth Hospital, Barbados over a 5 year period. There were 9 males and 14 females, with a median age of 38 years (range 14-84). Twelve had acute leukemia, 10 lymphoma (including 4 with solitary extra nodal lesions) and 1 smouldering subtype. Two patients had a past history of tropical spastic paraparesis/HTLV I associated myelopathy (TSM/HAM). The prognosis was poor, with only 3 complete responses to chemotherapy (CHOP) lasting from 9 to 36 months. We conclude that ATLL in Barbados is similar to the disease in the other Caribbean islands and Japan, except that in Barbados the age of onset is over a decade younger than in Japan.(AU)