Hemopoietic stem cell transplantation from a donor with indeterminate HTLV-1 status

To the Editor: A 42-year-old Chinese woman suffered from acute lymphoblastic leukemia (ALL) with t(9;22) and achieved complete remission with induction chemotherapy without imatinib mesylate (STI-571). She had one 40-year-old HLA identical sister from Fujian province, China. However, repeated human T cell lymphotrophic virus (HTLV-1+2) serology (Serodia, Fujirebio, Tokyo, Japan) on two occasions, 3 months apart, showed indeterminate HTLV-1 results, with Western blot reactivity to p21, p19, p26, p28, and p36 but not p32, p24, or GD21 (HTVL WB, version 2.4, Genelabs Diagnostics, Singapore). Both the donor and her spouse denied venereal exposure, overseas travel, or use of blood products or intravenous drugs. Polymerase chain reaction (PCR) tests for HTLV DNA sequences GD21, Gp46, and Pol on donor serum, whole blood, and mononuclear cell pellet were repeatedly negative [1]. After counseling, stem cell transplantation (SCT) was performed using cyclophosphamide and total body irradiation conditioning, and G-CSF mobilized peripheral blood stem cells were infused (9.88 10 8 /kg mononuclear cells, 2.07 10 6 /kg CD34). The patient engrafted with Grade 2 GVHD and cytomegalovirus re-activation was treated with steroids and gancyclovir. However, ALL relapsed on day 75. A second complete remission was achieved with STI-571, and a second unrelated donor SCT was planned. HTLV-1 serology and PCR in the recipient remained negative at 5 months. This is the first report of the use of HTLV-1 indeterminate donors for HSCT. Indeterminate HTLV status can be due to low-level viraemia or may be due to interfering virus or autoimmune conditions. The risk of true infection is higher in endemic areas. Although the local incidence of HTLV-1 seropositivity is below 0.004% [1], the proximity of Fujian to endemic areas (Japan and Taiwan) warranted extra caution. Among indeterminate Western results, certain HTLV Western blot patterns have stronger correlations with PCR positivity, and subsequent confirmed seropositivity for HTLV-1 [2]. However, in our case the Western blot pattern fall into the low risk category, and viral DNA detection was negative in all specimens. Hence, infective HTLV-1 viral particles were very unlikely to be present. Inadvertent transmission of HTLV-1 after SCT has been reported [3] and leads to early seroconversion due to transmission of infected lymphocytes. The negative HTLV tests at latest follow-up suggested that HSCT-related transmission of viral infection has not occurred in our case. The FDA required that all blood, tissue, and organ donors are screened for HTLV-1, but there is no absolute consensus on the use of HTLV-1 positive donors. The world marrow donor association listed HTLV-1 positivity as a contraindication to voluntary donation [4], but the national marrow match registry allows the use of such donors (except for cord blood) under certain circumstances. For HTLV-1 indeterminate status, there are no guidelines at all. In our case, the superior availability and outcome of matched sibling over unrelated HSCT justified the theoretical risk of HTLV-1 indeterminate serology [5]. It is uncertain whether the serological abnormality in the donor may be associated with inferior immunity leading to weakened graft versus leukemia effect and early relapse. WING Y. AU