Adult T‐cell leukemia–lymphoma in a pregnant woman diagnosed as a human T‐cell lymphotropic virus type 1 carrier

Fuchi, Naoki; Miura, Kiyonori; Imaizumi, Yoshitaka; Hasegawa, Hiroo; Yanagihara, Katsunori; Miyazaki, Yasushi; Masuzaki, Hiroaki

doi:10.1111/jog.12904

Cited by 5 publications

(6 citation statements)

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“…The maternal blood was collected before delivery from each pregnant participant, and placental villous tissue and cord blood were collected after delivery. Third-trimester placentas were collected after vaginal delivery or cesarean section, and a first-trimester placenta was collected from a chronic ATL patient after an induced abortion at 15 weeks gestation (84). Collected placental tissues were immediately stored in PBS at 4°C.…”

Section: Methodsmentioning

confidence: 99%

HTLV-1 targets human placental trophoblasts in seropositive pregnant women

Tezuka¹,

Fuchi²,

Okuma³

et al. 2020

Journal of Clinical Investigation

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Maternal blood during pregnancy, cord blood, and placental villous tissues at the time of delivery were obtained from subjects to measure the HTLV-1 proviral load (PVL) using real-time PCR. As shown in Figure 1A, HTLV-1 provirus was detected in the maternal blood of 248 of 254 subjects (97.6%), in the placental villous tissues of 140 of 254 subjects (55.1%), and in the cord blood samples of 6 of 254 subjects (2.4%). Overall, 248 women had PVL in the maternal blood, of whom 140 also had PVL in the placenta. Of these 140 women, 6 had PVL in the cord blood. Significant differences in the PVL were observed between the maternal blood, cord blood, and placental villous tissues (Figure 1A). The 248 pregnant carriers with PVL in the maternal blood were divided into those with PVL (n = 140) and without PVL (n = 108) in the placental tissue, and their clinical backgrounds were compared. Women with PVL in the placental tissue had a significantly higher peripheral blood PVL, higher antibody titers, and more multiparas compared with women with no PVL in the placental tissue (Table 1 and Figure 1B). These 2 groups did not differ in terms of birth weight and pregnancy complications (Table 1). There was no significant difference in the clinical backgrounds of pregnant women with HTLV-1 in the placenta when divided into those who tested positive versus negative for HTLV-1 in the cord blood (Supplemental Table 1). This was at least in part due to the small number of pregnant women testing positive for HTLV-1 in the cord blood. In addition, there were insufficient numbers of follow-up surveys of cases of MTCT by intrauterine transmission to allow statistical analysis. These issues are subjects for future investigation. A weak positive correlation between the PVLs in the maternal blood and in the placental villous tissues was observed (Figure 1C), whereas PVL in HTLV-1-positive cord blood samples did not correlate with PVL in the maternal blood or placental villous tissues of the same subject (Figure 1, D and E). To test the possibility that HTLV-1 provirus detected in cord blood was derived from maternal blood contamination of cord blood, microsatellite analysis was performed using short tandem repeat (STR) markers (25). Differences in the patterns of representative STR markers were observed between maternal blood-derived DNA and fetal placental villous tissue-and cord blood-derived DNA (Figure 1F). Similar results were obtained for all 6 samples that tested positive for HTLV-1 provirus in the cord blood. Furthermore, STR analysis and HTLV-1 PVL assay were used to examine how much maternal blood in the cord blood was required to detect a positive signal. A mixing rate of 20% (maternal/fetal cell ratio = 20:80) was the detection limit in the STR analysis, and a mixing rate of 5% (maternal/fetal cell ratio = 5:95) was the detection limit in the HTLV-1 PVL assay (Supplemental Figure 1). A previous study reported that the median rates of maternal blood contamination in the cord blood were 0.27% and 0.

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Section: Methodsmentioning

confidence: 99%

HTLV-1 targets human placental trophoblasts in seropositive pregnant women

Tezuka¹,

Fuchi²,

Okuma³

et al. 2020

Journal of Clinical Investigation

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“…In this case, chronic ATL with unfavorable prognosis (aggressive ATL) was diagnosed at 12 weeks of pregnancy. The pregnancy was terminated at 15 weeks following which the unfavorable factors (high lactate dehydrogenase (LDH) and low serum albumin) improved, with re-classification to favorable (indolent ATL) and a watchful waiting strategy was adopted (Fuchi et al, 2016). Interestingly, Fuchi et al (2018) also identified higher frequency of CD4 + CD25 + CD127 low/- cells and increased sIL-2R in HTLV-1 infected women compared with un-infected women 1 month after delivery in their recent study.…”

Section: Htlv-1 Infection In Pregnant Womenmentioning

confidence: 99%

Mother-to-Child HTLV-1 Transmission: Unmet Research Needs

Rosadas

Taylor

2019

Front. Microbiol.

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Mother-to-child transmission (MTCT) of Human T-cell lymphotropic virus type 1 (HTLV-1) causes lifelong infection. At least 5–10 million individuals worldwide are currently living with HTLV-1. Studies of regional variation are required to better understand the contribution of MTCT to the global burden of infection. Although most infected individuals remain asymptomatic ∼10% develop high morbidity, high mortality disease. Infection early in life is associated with a higher risk of disease development. Adult T-cell leukemia (ATL), which is caused by HTLV-1 and has a median survival of 8 months is linked to MTCT, indeed evidence of ATL following infection as an adult is sparse. Infective dermatitis also only occurs following neonatal infection. Whilst HTLV-1-associated myelopathy (HAM) follows sexual and iatrogenic infection approximately 30% of patients presenting with HAM/TSP acquired the infection through their mothers. HAM/TSP is a disabling neurodegenerative disease that greatly impact patient’s quality of life. To date there is no cure for HTLV-1 infection other than bone marrow transplantation for ATL nor any measure to prevent HTLV-1 associated diseases in an infected individual. In this context, prevention of MTCT is expected to contribute disproportionately to reducing both the incidence of HTLV-1 and the burden of HTLV-1 associated diseases. In order to successfully avoid HTLV-1 MTCT, it is important to understand all the variables involved in this route of infection. Questions remain regarding frequency and risk factors for in utero peri-partum transmission whilst little is known about the efficacy of pre-labor cesarean section to reduce these infections. Understanding the contribution of peripartum infection to the burden of disease will be important to gauge the risk-benefit of interventions in this area. Few studies have examined the impact of HTLV-1 infection on fertility or pregnancy outcomes nor the susceptibility of the mother to infection during pregnancy and lactation. Whilst breast-feeding is strongly associated with transmission and avoidance of breast-feeding a proven intervention little is known about the mechanism of transmission from the breast milk to the infant and there have been no clinical trials of antiretroviral therapy (ARV) to prevent this route of transmission.

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“…ATL in pregnancy has been reported five times as individual case reports since first described in 1977, two cases from USA and three from Japan [8][9][10][11][12]. In Japan, the median age of ATL diagnosis is 67.5…”

Section: Introductionmentioning

confidence: 99%

“…ATL in pregnancy has been reported five times as individual case reports since first described in 1977, two cases from USA and three from Japan [ 8 , 9 , 10 , 11 , 12 ]. In Japan, the median age of ATL diagnosis is 67.5 years [ 5 ], and so presentation of ATL in pregnancy is expected to be a relatively rare event.…”

Section: Introductionmentioning

confidence: 99%

“…The previous described reports are of three cases of acute ATL and one lymphoma case all managed with chemotherapy, and the mothers typically died soon after delivery. Fuchi et al described a chronic unfavourable case in a pregnant woman, who was previously known to be an asymptomatic carrier (diagnosed in a previous pregnancy), and the pregnancy was terminated at 15 weeks which was reported to be associated with favourable clinical outcome [ 9 ]. ATL is a heterogeneous disease, and a recent consensus report suggested patients with lymphoma subtypes should be managed with chemotherapy‐based protocols [ 15 , 16 ].…”

Section: Introductionmentioning

confidence: 99%

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Adult T cell leukaemia/lymphoma (ATL) in pregnancy: A UK case series

Aval

Boullier

Lyall

et al. 2020

eJHaem

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Introduction Chronic infection with human T‐cell lymphotropic virus type‐1 (HTLV‐1) may result in aggressive adult T‐cell leukaemia/lymphoma (ATL) in 4‐6% carriers. The majority of this risk arises in carriers infected during infancy, and so each infant has ∼25% lifetime risk. Other risk factors include a family history of ATL. Antenatal HTLV‐1 screening is not undertaken in the UK. Methods Here we describe four cases of ATL diagnosed during pregnancy and describe strategies to minimise HTLV‐1 transmission to neonates. Results/conclusion These cases highlight undiagnosed HTLV‐1 in pregnancy which allows ongoing mother to child vertical transmission and risk of future ATL. We recommend the UK National Screening Committee incorporate HTLV‐1 serology into antenatal screening.

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Adult T‐cell leukemia–lymphoma in a pregnant woman diagnosed as a human T‐cell lymphotropic virus type 1 carrier

Cited by 5 publications

References 12 publications

HTLV-1 targets human placental trophoblasts in seropositive pregnant women

HTLV-1 targets human placental trophoblasts in seropositive pregnant women

Mother-to-Child HTLV-1 Transmission: Unmet Research Needs

Adult T cell leukaemia/lymphoma (ATL) in pregnancy: A UK case series

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