Onset Of Adult T-cell Leukemia/lymphoma Research Articles

The development of adult T cell leukemia/lymphoma in renal transplant recipients: report of two cases with literature review

BackgroundsTherefore, reports on the risk of HTLV-1-related diseases in organ transplantation have increased in recent years, and the management of HTLV in renal transplantation remains a challenge.Patients and methodsWe retrospectively analyzed four HTLV-1-positive recipients or donors among 89 renal transplantation cases from 2006 to 2021.ResultsAmong the four HTLV-1-positive recipients, two patients developed adult T cell leukemia/lymphoma (ATL) derived from recipients at approximately 3 years (1016 days and 1195 days) after renal transplantation. Case 1 developed lymphoma-type ATL (an extranodal primary cutaneous variant), including skin and pulmonary lesions. The patient achieved CR with FK tapering and CHOP therapy following cord blood stem cell transplantation. However, the patient died 101 days after ATL development because of a severe fungal infection. Case 2 developed acute-type ATL with an unusual phenotype of CD4+8+30+. The patient was treated with FK tapering and palliative therapy because of poor PS. Notably, in case 1, histopathological findings showed high numbers of PD-1-positive TIL cells in ATL, suggesting exhausted T cells and a correlation with the early onset of ATL. Furthermore, in Case 2, histopathological findings revealed CD 30 expression in ATL cells, suggesting the importance of CD 30 in ATL development. Importantly, case 2 showed typical driver mutations, including CCR4 truncation mutations of the C-terminal, TBL1XR1 mutation, and TP53 mutation in the splice site. Notably, our present study and our previous study on renal transplantation strongly indicated that two out of two and one out of 59 “recipient” positive cases developed ATL, respectively. Furthermore, our previous nationwide study 4 out of 10 “donor” positive cases developed HAM. These findings showed that ATL may be derived from HTLV-I+ recipient cells and HAM may be derived from HTLV-1+ donor cells, although the precise mechanism remains unknown.ConclusionsThus, early onset and rapid progression of ATL with poor outcomes should be considered in HTLV-1 endemic areas. Furthermore, immunological or genetic mechanisms may be related to the development of ATL after renal transplantation. We believe that the mechanism of onset of ATL after transplantation may be important when considering the immune environment of ATL itself.

HTLV-1 persistent infection and ATLL oncogenesis.

Human T-cell leukemia virus type 1 (HTLV-1) is an oncogenic retrovirus; whereas HTLV-1 mainly persists in the infected host cell as a provirus, it also causes a malignancy called adult T-cell leukemia/lymphoma (ATLL) in about 5% of infection. HTLV-1 replication is in most cases silent in vivo and viral de novo infection rarely occurs; HTLV-1 rather relies on clonal proliferation of infected T cells for viral propagation as it multiplies the number of the provirus copies. It is mechanistically elusive how leukemic clones emerge during the course of HTLV-1 infection in vivo and eventually cause the onset of ATLL. This review summarizes our current understanding of HTLV-1 persistence and oncogenesis, with the incorporation of recent cutting-edge discoveries obtained by high-throughput sequencing.

Metabolic abnormalities in adult T-cell leukemia/lymphoma and induction of specific leukemic cell death using photodynamic therapy

Adult T-cell leukemia/lymphoma (ATL) is an aggressive T-cell neoplasm caused by human T-cell leukemia virus type I (HTLV-I). Therapeutic interventions have not been associated with satisfactory outcomes. We showed that the porphyrin metabolic pathway preferentially accumulates the endogenous photosensitive metabolite, protoporphyrin IX (PpIX) in ATL, after a short-term culture with 5-aminolevulinic acid (ALA). PpIX accumulated 10–100-fold more in ATL leukemic cells when compared to healthy peripheral blood mononuclear cells (PBMCs). Patient specimens showed dynamic changes in flow cytometry profiles during the onset and progression of ATL. Furthermore, 98.7% of ATL leukemic cell death in the ATL patient specimens could be induced with 10 min of visible light exposure, while 77.5% of normal PBMCs survived. Metabolomics analyses revealed that a specific stage of the metabolic pathway progressively deteriorated with HTLV-I infection and at the onset of ATL. Therefore, this method will be useful in diagnosing and identifying high-risk HTLV-I carriers with single cell resolutions. Photodynamic therapy in the circulatory system may be a potential treatment due to its highly-specific, non-invasive, safe, simultaneous, and repeatedly-treatable modalities.

CADM1 Overexpression and CD7 Downregulation in Strongyloides stercoralis and HTLV-1 Coinfection as Possible Markers for Adult T-cell Leukemia/Lymphoma progression

Background Human T-cell lymphotropic virus (HTLV-1) is a retrovirus endemic in Latin America, Africa, and Asia. Increasing numbers are being reported in the United States. HTLV-1 causes Adult T-cell Leukemia/Lymphoma (ATL) in 3–5% of HTLV-1 carriers, usually only after a prolonged latent period. Co-infection with the nematode Strongyloides stercoralis (SS) is associated with early onset of ATL. The exact mechanism by which SS accelerates ATL development in HTLV-1 subjects is not understood. CADM1 has been recently identified as a surface marker of HTLV-1 infected cells; CD7 is a probable marker of early cell transformation. We hypothesize that previous SS infection will increase the proportion of infected T cells (CADM1+) and lead to transformation of infected cells (CADM1+CD7low) in HTLV-1 subjects.Methods In this pilot study, we tested seven subjects that were diagnosed with HTLV-1 between 2006 and 2008 and actively followed up at the HTLV-1 Cohort Clinic at the Tropical Medicine Institute in Lima, Peru. Five had previous SS infection. We performed surface flow cytometry staining of peripheral blood mononuclear cells with monoclonal antibodies against CADM1, CD7, CD4, and CD3. Current SS infection was ruled out by the Baermann technique in a stool sample.ResultsAverage age was 53 years (range 30–79). Average time since diagnosis of HTLV-1 was 10 years (range 9–11). One 30-year-old patient with prior SS infection was diagnosed with ATL and hospitalized in the ICU at the time of follow-up and excluded from group comparison. There was a trend for higher proportions of CADM1+ T-cells in subjects with previous SS co-infection compared with those without SS (median 16.20% vs. 9.55%, P = 0.13, Mann–Whitney). The proportion of PBMCs that were CADM1+CD7− was also increased in some of those with previous SS (Figure 1).Conclusion Our pilot data suggest that SS co-infection is associated with prolonged effects on HTLV-1 infection. We noted trends towards increased numbers of HTLV-1 infected cells (CADM1+) and a predisposition towards malignant transformation (CADM1+CD7low). Further studies are needed to confirm this observation and to determine whether CADM1 and CD7 expression may be useful as a screening tool to monitor HTLV-1 subjects at high risk of developing ATL.Figure 1.Representative flow cytometry.Disclosures All authors: No reported disclosures.

Adult T-cell leukemia/lymphoma in patients with head and neck cancer after S-1 chemotherapy.

One in 1000-3000 carriers of human T-cell leukemia virus type 1 (HTLV-1) develops adult T-cell leukemia/lymphoma (ATLL) per year; however, the pathogenic mechanism is not completely clear. We have observed that some patients with squamous cell carcinoma (SCC) develop ATLL during treatment at our hospital. The aim of this study was to examine treatment factors associated with onset of ATLL through an evaluation of the therapeutic background of these patients. The impact of radiotherapy, chemotherapy and surgery on occurrence of ATLL was evaluated in 146 patients with head and neck SCC who were treated at our hospital between April 2010 and December 2013. Of 146 patients, 17 were HTLV-1 positive and 6 developed ATLL. There was a significant relationship between ATLL development and administration of S-1 chemotherapy (p=0.0003), but not with use of radiotherapy, surgery or other drugs. The involvement of S-1 chemotherapy in ATLL development suggests that a test for HTLV-1 antibody should be performed before treatment and that S-1 should not be administered in HTLV-1 positive patients with head and neck carcinoma.

The Major Histocompatibility Complex Class II Transactivator CIITA Inhibits the Persistent Activation of NF-κB by the Human T Cell Lymphotropic Virus Type 1 Tax-1 Oncoprotein.

Human T cell lymphotropic virus type 1 (HTLV-1) Tax-1, a key protein in HTLV-1-induced T cell transformation, deregulates diverse cell signaling pathways. Among them, the NF-κB pathway is constitutively activated by Tax-1, which binds to NF-κB proteins and activates the IκB kinase (IKK). Upon phosphorylation-dependent IκB degradation, NF-κB migrates into the nucleus, mediating Tax-1-stimulated gene expression. We show that the transcriptional regulator of major histocompatibility complex class II genes CIITA (class II transactivator), endogenously or ectopically expressed in different cells, inhibits the activation of the canonical NF-κB pathway by Tax-1 and map the region that mediates this effect. CIITA affects the subcellular localization of Tax-1, which is mostly retained in the cytoplasm, and this correlates with impaired migration of RelA into the nucleus. Cytoplasmic and nuclear mutant forms of CIITA reveal that CIITA exploits different strategies to suppress Tax-1-mediated NF-κB activation in both subcellular compartments. CIITA interacts with Tax-1 without preventing Tax-1 binding to both IKKγ and RelA. Nevertheless, CIITA affects Tax-1-induced IKK activity, causing retention of the inactive p50/RelA/IκB complex in the cytoplasm. Nuclear CIITA associates with Tax-1/RelA in nuclear bodies, blocking Tax-1-dependent activation of NF-κB-responsive genes. Thus, CIITA inhibits cytoplasmic and nuclear steps of Tax-1-mediated NF-κB activation. These results, together with our previous finding that CIITA acts as a restriction factor inhibiting Tax-1-promoted HTLV-1 gene expression and replication, indicate that CIITA is a versatile molecule that might also counteract Tax-1 transforming activity. Unveiling the molecular basis of CIITA-mediated inhibition of Tax-1 functions may be important in defining new strategies to control HTLV-1 spreading and oncogenic potential. HTLV-1 is the causative agent of human adult T cell leukemia-lymphoma (ATLL). The viral transactivator Tax-1 plays a central role in the onset of ATLL, mostly by deregulating the NF-κB pathway. We demonstrate that CIITA, a key regulator of adaptive immunity, suppresses Tax-1-dependent activation of NF-κB by acting at several levels: it retains most of Tax-1 and RelA in the cytoplasm and inhibits their residual functional activity in the nucleus. Importantly, this inhibition occurs in cells that are targets of HTLV-1 infection. These findings are of interest in the field of virology because they expand the current knowledge of the functional relationship between viral products and cellular interactors and provide the basis for a better understanding of the molecular countermeasures adopted by the host cell to antagonize HTLV-1 spreading and transforming properties. Within this framework, our results may contribute to the establishment of novel strategies against HTLV-1 infection and virus-dependent oncogenic transformation.

HTLV-1-targeted immunotherapy.

Adult T-cell leukemia/lymphoma (ATL) is a HTLV-1 induced T-cell malignancy with an extremely poor prognosis. There is a long latency period between HTLV-1 infection and the onset of ATL, which indicates the existence of multistep mechanisms of leukemogenesis in the infected cells. Tax, which is encoded by the HTLV-1 pX region, plays a crucial role in HTLV-1 leukemogenesis and is a major target of CTL. We developed an anti-ATL therapeutic vaccine consisting of autologous dendritic cells that is pulsed with Tax peptides (Tax-DC). The vaccination protocol was completed with three injections at a 2-week interval, within one month. Good quality of life and long-term treatment-free survival were observed for more than 3 years in two of the three patients enrolled in the pilot study. Furthermore, the proviral load remained mostly around the carrier level, with minor fluctuation, after vaccination. Tax-specific proliferative CTL responses were observed in all cases and sporadically augmented responses were also subsequently detected. The Tax-DC vaccine might be a well-tolerated and long-lasting maintenance therapy that is acceptable even for elderly patients. Based on the encouraging results, we are now conducting a clinical trial of Tax-DC vaccine combined with anti-CCR4 antibody to enhance the efficacy of the vaccine as next-generation immunotherapy.

HTLV-1 bZIP Factor RNA and Protein Impart Distinct Functions on T-cell Proliferation and Survival.

Infection of T cells with human T-cell leukemia virus type-1 (HTLV-1) induces clonal proliferation and is closely associated with the onset of adult T-cell leukemia-lymphoma (ATL) and inflammatory diseases. Although Tax expression is frequently suppressed in HTLV-1-infected cells, the accessory gene, HTLV-1 bZIP factor (HBZ), is continuously expressed and has been implicated in HTLV-1 pathogenesis. Here, we report that transduction of mouse T cells with specific mutants of HBZ that distinguish between its RNA and protein activity results in differential effects on T-cell proliferation and survival. HBZ RNA increased cell number by attenuating apoptosis, whereas HBZ protein induced apoptosis. However, both HBZ RNA and protein promoted S-phase entry of T cells. We further identified that the first 50 bp of the HBZ coding sequence are required for RNA-mediated cell survival. Transcriptional profiling of T cells expressing wild-type HBZ, RNA, or protein revealed that HBZ RNA is associated with genes involved in cell cycle, proliferation, and survival, while HBZ protein is more closely related to immunological properties of T cells. Specifically, HBZ RNA enhances the promoter activity of survivin, an inhibitor of apoptosis, to upregulate its expression. Inhibition of survivin using YM155 resulted in impaired proliferation of several ATL cell lines as well as a T-cell line expressing HBZ RNA. The distinct functions of HBZ RNA and protein may have several implications for the development of strategies to control the proliferation and survival mechanisms associated with HTLV-1 infection and ATL.

Cutaneous manifestations of human T-cell lymphotrophic virus type-1-associated adult T-cell leukemia/lymphoma: retrospective study in Martinique

Background Adult T cell leukemia/lymphoma (ATLL) is an aggressive lymphoma that occurs in 2–5% of HTLV-1 infected persons after several decades. Cutaneous manifestations often reveal or accompany the diagnosis of ATLL patients. No data exist regarding cutaneous involvement of adult T-cell leukemia/lymphoma (ATLL) in Martinique. We sought to describe skin involvement characteristics at onset of ATLL in Martinique.

Landscape of Genetic Alterations in Adult T-Cell Leukemia/Lymphoma

Adult T-cell leukemia/lymphoma (ATL) is a distinct form of peripheral T-cell lymphoma, which is etiologically associated with human T-cell leukemia virus type 1 (HTLV-1) infection during early infancy. Although HTLV-1 can effectively immortalize human T cells, there is a long latency period of ~50 years before the onset of ATL, suggesting that HTLV-1 infection alone may be insufficient for the development of ATL, but additional acquired genetic events that accumulate during the later life are essential for the development of ATL. However, such somatic alterations underlying the pathogenesis of ATL have not been fully elucidated.To obtain a complete registry of genetic alterations in ATL, we performed an integrated genetic study, in which whole-genome/exome and RNA sequencing (RNA-seq) was performed together with array-based methylation and genomic copy number analysis among a cohort of 50 paired ATL samples, followed by extensive validation using targeted deep sequencing of detected mutations in > 400 follow-up samples. Compared with other lymphoid malignancies, ATL cells carried higher numbers of mutations, copy number alterations, and rearrangements than in other lymphoid malignancies, suggesting the presence of global genomic instability in ATL. In addition to previously reported mutational targets in ATL (TP53,TCF8, and FAS) and known targets frequently mutated in other lymphoid malignancies (CARD11, GATA3, IRF4, POT1, and RHOA), we identified a variety of highly recurrent mutations affecting previously unknown mutational targets, many of which are involved in T-cell development, activation and migration, immunosurveillance, and transcriptional regulation. Molecular and functional analysis using human T-cell leukemia cell lines showed that some of these novel mutations actually augment T-cell receptor signaling, validating their biological significance in ATL. A comparison of mutations among disease subtypes revealed that several subtype-specific mutations, including TP53, CD58, IRF4 and TBL1XR1 mutations in acute and lymphoma types, and STAT3mutation in chronic and smoldering types, suggesting that different oncogenic mechanisms underlie different ATL subtypes. Furthermore, ATL cells had a distinct pattern of copy number changes and genomic rearrangements. Interestingly, their gene targets showed a significant overlap to mutational targets. Surprisingly, somatic focal deletions involving the 14q31.1 locus were observed in all the cases examined by whole-genome sequencing and therefore are thought to uniquely characterize ATL genomes, although their gene targets remained to be identified. Like other regions also frequently deleted in ATL, such as 7q31.1 and 1p21.3 loci, these deletions were thought to reflect high levels of genetic instability. Finally and conspicuously, pathway analysis revealed that multiple genes involved in the Tax interactome were systematically altered in ATL, although Tax itself underwent gene silencing in most cases. These data suggested that ATL cells can escape from cytotoxic T-lymphocytes by silencing immunogenic Tax expression, while developing alternative oncogenic mechanisms through acquiring somatic mutations or copy number alterations in the Tax-related pathway. Our findings suggest that deregulated T-cell functionalities caused by genetic alterations, especially those associated with HTLV-1 Tax oncoprotein, are central to ATL pathogenesis, and provide a novel clue to contrive new diagnostics and therapeutics for this intractable disease. DisclosuresNo relevant conflicts of interest to declare.

Molecular Characterization Of Adult T-Cell Leukemia/Lymphoma

Adult T-cell leukemia/lymphoma (ATL) is an aggressive form of peripheral T-cell lymphoma (PTCL), which is etiologically associated with human T-lymphotropic virus type I (HTLV-1) infection during early infancy. Although HTLV-1 can effectively immortalize T-cells, there is a long latency period of ∼50 years prior to the onset of ATL, suggesting that HTLV-1 infection alone may not be sufficient for the development of ATL, but additional acquired genetic hits that occur in immortalized T-cells during the later life are essential for its pathogenesis. However, little has been known about those genetic hits that are involved in the pathogenesis of ATL.The purpose of this study is to understand the genetic basis of ATL, 32 cases with different ATL subtypes, including acute (N=15), chronic (N=6), lymphoma (N=10), smoldering (N=1) types were analyzed by whole exome sequencing as well as copy number analysis. With a mean coverage of 119, 94% of the target sequences were analyzed at more than 20 depth on average. A total of 2,862 somatic changes were detected in 32 cases with a true positive rate of 99% (329 of the 334 tested were confirmed by PCR-based deep sequencing). These consisted of 2,512 missense mutations, 174 nonsense mutations, 65 splice-site mutations, and 111 indels. The mutation rate of 89 (44-227) per sample was significantly higher than that in acute myeloid leukemia (7.3–13), myelodysplastic syndromes (9.2) and chronic lymphocytic leukemia (11.5). Recurrent mutations were observed in 350 genes, of which 192 were considered to be significantly mutated (q < 0.05) compared to background mutation rates (1.79 mutations per megabase).To investigate significantly mutated pathways, each pathway registered in the Kyoto Encyclopedia of Genes and Genomes, BioCarta, Reactome, Sigma-Aldrich and Signaling Transduction KE was tested on the basis of the background mutation rate observed in whole-exome sequencing data, which revealed a number of significantly mutated functional pathways, including pathways involeved in T cell receptor signaling, leukocyte trans-endothelial migration, VEGF and WNT signalings and other signaling pathways.Genes for epigenetic regulations were also among the frequent targets of gene mutations. We performed targeted deep sequencing of TET2, IDH1/2 and DNMT3A in 182 ATL cases. In total, 19 TET2 mutations were identified in 16 cases (8.7%). Different subtypes of ATL were almost evenly affected with 9 out of 67 acute, 3 out of 42 chronic and 4 out of 56 lymphoma types having TET2 mutations. Less frequent mutations of IDH2 and DNMT3A (both 1%) were also identified. Our findings on genetic alterations provide a novel insight into the pathogenesis of ATL. Disclosures:No relevant conflicts of interest to declare.

P53 dysfunction precedes the activation of nuclear factor-κB during disease progression in mice expressing Tax, a human T-cell leukemia virus type 1 oncoprotein

Transgenic (Tg) mice expressing Tax, a human T-cell leukemia virus type 1 (HTLV-1) oncoprotein, develop mature T-cell leukemia/lymphoma. The leukemic cells in Tg mice expressing Tax show p53 dysfunction and nuclear factor-κB (NF-κB) activation, similar to that seen in adult T-cell leukemia/lymphoma (ATLL) cells from patients infected with HTLV-1. However, it is unclear when these effects occur in HTLV-1 carriers during the development of ATLL. Here, we examined p53 function and NF-κB activity before the onset of leukemia in Tax-expressing Tg (Tax-Tg) mice between 4 and 25 months of age. At 4-10 months of age, 71% of mice showed p53 inactivation, without evidence for NF-κB activation, even though tax expression was consistent from 4 to 25 months of age. The decline in p53 function resulted from decreased p53 accumulation after DNA damage. From 11 months of age onward, 75% of mice showed p53 dysfunction and 37.5% showed constitutive NF-κB activation with the components of p50 and RelB. An NF-κB inhibitor, dehydroxymethylepoxyquinomicin (DHMEQ), reduced NF-κB activity (i.e. p50/RelB) but did not restore p53 function. In vivo, treatment with DHMEQ until 24 months of age prevented the onset of T-cell leukemia in Tax-Tg mice. These results suggest that the Tax-induced decline in p53 function, which is independent of NF-κB activation in the early stage, might be the first stage in the onset of ATLL. NF-κB activity is involved in the later stages of ATLL onset.

Successful treatment of young-onset adult T cell leukemia/lymphoma and preceding chronic refractory eczema and corneal injury by allogeneic hematopoietic stem cell transplantation

Only some carriers of human T cell lymphotropic virus type I (HTLV-1) develop adult T cell leukemia/lymphoma (ATLL) after a long latency period, and an association has been reported between chronic refractory eczema, known as infective dermatitis, and young-onset ATLL. A 25-year-old female developed ATLL and underwent allogeneic hematopoietic stem cell transplantation (HSCT) in non-remission. She had chronic refractory eczema and corneal injury at the onset of ATLL. Remission of ATLL was achieved, and the HTLV-1 proviral load decreased after HSCT. In addition, her pre-existing eczema and corneal injuries almost disappeared. More than a year has passed since the transplantation was performed, and she has had no recurrence of either ATLL or lesions in the skin and eye. Her clinical course suggests a possible association between skin and eye lesions and HTLV-1 infection. Changes in the immunological condition after HSCT might play a key role. Special attention is needed when HTLV-1 carriers develop eye or skin lesions.

Trends of incidence rate of adult T‐cell leukemia/lymphoma in an HTLV‐1 endemic area in Japan

Trends of incidence rate of adult T‐cell leukemia/lymphoma in an HTLV‐1 endemic area in Japan

Human T-cell Leukemia Virus Type I Tax Down-regulates the Expression of Phosphatidylinositol 3,4,5-Trisphosphate Inositol Phosphatases via the NF-κB Pathway

Human T-cell leukemia virus type I (HTLV-I) is an oncogenic retrovirus that causes adult T-cell leukemia/lymphoma (ATLL). The virus encodes an oncoprotein, Tax, which functions in transcriptional regulation, cell cycle control, and transformation. Through its pleiotropic actions, Tax plays critical roles in leukemogenesis. We have previously reported that PTEN and SHIP-1, PIP3 inositol phosphatases that negatively regulate the phosphatidylinositol (PI) 3-kinase signaling cascade, are disrupted in ATLL neoplasias. Overactivation of PI3-kinase signaling has an essential role in both development of ATLL-specific nuclear polymorphisms and onset of ATLL. We report here that both PTEN and SHIP-1 are down-regulated by HTLV-I Tax through the NF-kappaB signaling pathway. Tax expression up-regulated phosphorylated Akt, a downstream serine/threonine kinase in the PI3-kinase signaling cascade. Transduction of NF-kappaB p65, which mimics the activation of NF-kappaB signaling, also suppressed these phosphatases. An IkappaBDeltaN mutant that inhibits the activation of NF-kappaB prevented PIP3 phosphatase down-regulation by Tax. The underlying mechanism of NF-kappaB-mediated suppression of PIP3 phosphatases involved sequestration of the coactivator p300 by p65. These down-regulations of PIP3 phosphatases were found to be essential for the Tax-induced cell proliferation. Thus, our results suggest that HTLV-I Tax down-regulates PIP3 phosphatases through the NF-kappaB pathway, resulting in increased activation of the PI3-kinase signaling cascade in human T-cells and contributing to leukemogenesis.

Infection of human T-cell leukemia virus type I and development of human T-cell leukemia lymphoma in patients with hematologic neoplasms: a possible linkage to blood transfusion

Among 354 adult patients with either hematological malignancy or aplastic anemia, eight were positive for anti-HTLV-I antibodies; six of eight had received multiple transfusions. There was an approximately 3.5-fold increase (P less than .001) of HTLV-I seropositivity in the patients with hematologic disease (8 of 354, 2.23%) compared to the healthy adults older than 20 years (34 of 5252, .65%). Two hematological patients, one with Hodgkin's disease and one with acute promyelocytic leukemia, were found to be positive for HTLV-I, and developed and died of adult T-cell leukemia/lymphoma (ATL) subsequently. Both were long-term survivors of the primary disease and had received multiple transfusions. The latent period from blood transfusion to onset of ATL was 6 months and 11 years, respectively. Immunocompromised patients, who were seropositive for HTLV-I, may be at increased risk for ATL compared to healthy carriers of HTLV-I, and the latent period may be shorter.

Infection of Human T-Cell Leukemia Virus Type I and Development of Human T-Cell Leukemia/Lymphoma in Patients With Hematologic Neoplasms: A Possible Linkage to Blood Transfusion

AbstractAmong 354 adult patients with either hematological malignancy or aplastic anemia, eight were positive for anti- HTLV-I antibodies; six of eight had received multiple transfusions. There was an approximately 3.5-fold increase (P < .001) of HTLV-I seropositivity in the patients with hematologic disease (8 of 354, 2.23%) compared to the healthy adults older than 20 years (34 of 5252, .65%). Two hematological patients, one with Hodgkin's disease and one with acute promyelocytic leukemia, were found to be positive for HTLV-I, and developed and died of adult T-cell leukemia/lymphoma (ATL) subsequently. Both were longterm survivors of the primary disease and had received multiple transfusions. The latent period from blood transfusion to onset of ATL was 6 months and 11 years, respectively. Immunocompromised patients, who are seropositive for HTLV-I, may be at increased risk for ATL compared to healthy carriers of HTLV-I, and the latent period may be shorter.