T-cell Leukemia-lymphoma Patients Research Articles

Analysis of Clinical Picture of Chronic Inflammatory Demyelinating Polyneuropathy in Adult T-Cell Leukemia-Lymphoma Patients after Allogeneic Stem Cell Transplantation

Background:Chronic inflammatory demyelinating polyneuropathy (CIDP) is a progressive or recurrent neurological disorder caused by diffuse demyelination of peripheral nerves combined with muscle weakness and/or a sensory disorder. Abnormalities of both humoral and cellular immunity have been suggested to be involved in CIDP pathogenesis. But neither specific autoantibodies nor antigens have been found in patient sera. A few reports have described CIDP that develop after allogeneic stem cell transplantation (allo-SCT). However, CIDP developing after allo-SCT to treat adult T-cell leukemia-lymphoma (ATL) patients has never been described. We encountered ATL patients who developed CIDP after allo-SCT and we analyzed their disease profiles. This is the first report about CIDP in ATL patients who received allo-SCT.Methods:We evaluated 46 ATL patients who underwent allo-SCT. Three patients developed polyneuropathy and we performed a nerve conduction study, magnetic resonance imaging (MRI), and measurement of the levels of neopterin and CXCL10. Neopterin is a small molecule derived from guanosine triphosphate (GTP) that is produced by monocytes and macrophages in vivo, and is a sensitive marker of central nervous system (CNS) inflammation. CXCL10 is an inflammatory chemokine that binds to CXCR3 (expressed specifically on Th1 cells). CXCL10 is also a sensitive marker of CNS inflammation. Neopterin and CXCL10 are known to be elevated in CSF of patients with human T-cell leukemia virus-1 associated myelopathy (HAM). We analyzed their expression to exclude the possibility of HAM.Results:46 ATL patients, aged 28-71 years (median 59), 25 males and 21 females, we reviewed. Of these patients, three patients developed polyneuropathy after allo-SCT. Table 1 shows the patient profiles. The three patients achieved and maintained complete remission (CR) after allo-SCT but developed chronic GVHD involving multiple organ. The time of polyneuropathy onset varied from 1-89 months after allo-SCT. Table 2 shows the CSF data. A diagnosis of HAM requires that the anti-HTLV-1 antibody titer should be >16 times in both the serum and the CSF. In two patients, the CSF anti-HTLV-1 antibody titers were <2 times. In the other patient, though the anti-HTLV-1 antibody titer in the CSF was 4 times, thus weakly positive, the deep tendon reflexes were reduced and pathological reflexion was not apparent, suggesting that the patient doesn't have myelopathy. Based on these, three patients did not have HAM. Elevation of neopterin and/or CXCL10 in CSF was suggested to be related with not HAM but nonspecific immunological findings. They had progressive or recurrent neurological disorder lasting more than 2 months and diffuse demyelination of peripheral nerves proved by nerve conduction study. CSF examination showed albuminocytologic dissociation. We diagnosed three patients as CIDP according to diagnostic criteria (EFNS/PNS guidelines). Neither ATL nor HAM is likely to cause CIDP in three patients. Also, some drugs including Tac have been suggested to induce CIDP. Some patients who underwent heart or liver transplantation developed CIDP 2-10 weeks after commencing Tac. Two of our present patients were taking Tac, but the timing of CIDP onset was much later than that of other case reports. The performance status of all three patients was 3-4 and their daily life was severely disturbed. CIDP treatments include corticosteroids, intravenous immunoglobulin (IvIg), and plasmapheresis, but neither corticosteroids nor IvIg were effective in our three patients.ConclusionIn the previous reports, chronic myelogenous leukemia, Hodgkin's lymphoma, non-Hodgkin's lymphoma, aplastic anemia, multiple myeloma, acute myelogenous leukemia, and acute lymphoblastic leukemia developed CIDP after SCT. However, CIDP has never before been reported in ATL patients who underwent allo-SCT. As far as we know, this is the first report about CIDP in ATL patients who received allo-SCT. All of our patients developed GVHD after allo-SCT. One report of CIDP after SCT found infiltrations of CD8-positive cells in nerve biopsy material. It has been suggested that CIDP may be caused by an immunological reaction developing after allo-SCT. Since ATL patients usually have immunological abnormality due to perturbed T-cell function, we need further study to elucidate whether immunological abnormality of ATL is affecting the onset of CIDP after allo-SCT. [Display omitted] DisclosuresNo relevant conflicts of interest to declare.

Chronic inflammatory demyelinating polyneuropathy in adult T-cell leukemia-lymphoma patients following allogeneic stem cell transplantation.

Chronic inflammatory demyelinating polyneuropathy in adult T-cell leukemia-lymphoma patients following allogeneic stem cell transplantation.

Reactivation of hepatitis B virus (HBV) infection in adult T-cell leukemia-lymphoma patients with resolved HBV infection following systemic chemotherapy.

Reactivation of hepatitis B virus (HBV) infection may occur in adult T-cell leukemia-lymphoma (ATL) patients with resolved HBV infection who receive monotherapy with the anti-CC chemokine receptor 4 monoclonal antibody, mogamulizumab. However, there is little evidence regarding the incidence and characteristics of HBV reactivation in ATL patients receiving systemic chemotherapy, including the use of this antibody. We conducted a retrospective study for 24 ATL patients with resolved HBV infection underwent regular HBV DNA monitoring to assess HBV reactivation in Nagoya City University Hospital between January 2005 and June 2013. With median HBV DNA follow-up of 238days (range 57-1420), HBV reactivation (defined as the detection of HBV DNA) was observed in three (12.5%) of 24 patients with resolved HBV infection. No hepatitis due to HBV reactivation occurred in those patients who were diagnosed with HBV DNA levels below 2.1 log copies/mL and who received antiviral drugs. Mogamulizumab was administered prior to HBV reactivation in two of three HBV-reactivated patients. In the mogamulizumab era, further well-designed prospective studies are warranted to estimate the incidence of HBV reactivation and to establish regular HBV DNA monitoring-guided preemptive antiviral therapy for such patients.

Trans-Activation of the human T-cell leukemia virus long terminal repeat correlates with expression of the x-lor protein

Cell lines established directly from adult T-cell leukemia-lymphoma patients or immortalized by human T-cell leukemia virus type I (HTLV-I) in vitro that do not produce complete HTLV virions were characterized both for the content of viral proteins and for the presence of trans-acting factors activating gene expression under the control of the HTLV long terminal repeat. The expression of the 42-kilodalton HTLV x-lor product correlated with trans-activation of the long terminal repeat. The implications of this study for understanding the role of the HTLV x-lor product in the initiation and maintenance of T-lymphocyte transformation are discussed.

Transformation of different phenotypic types of human bone marrow T-lymphocytes by HTLV-1.

Fresh bone marrow mononuclear leukocytes were used as a target for infection by human T-cell leukemia-lymphoma virus subgroup 1 (HTLV-1) by co-cultivation with virus-positive cell lines. The lines were established from T-cell leukemia-lymphoma patients or HTLV-1-transformed human umbilical cord-blood T cells. Clumps of transformed cells became visible by 2-3 weeks after infection and developed at a high frequency (greater than 90%) in the bone marrow samples used. Stimulation of target cells with lymphocyte mitogens facilitated this process but was not absolutely required. Unlike fresh or cultured cells from HTLV-1-positive adult leukemia-lymphoma patients and HTLV-1-transformed cord-blood T cells, which usually have an OKT 4/leu 3a surface phenotype, the transformed bone marrow cells frequently fell into one of three categories based on their reactivity with cell-specific monoclonal antibodies. These included populations of cells that were predominantly; (1) OKT 4/leu 3a-positive, (2) OKT 8/leu 2a-positive, and (3) cells expressing neither phenotype. Fresh bone marrow provided a rapid and efficient system for the assessment of HTLV-1 infection. The type of bone marrow cells transformed in vitro suggests that HTLV-1 can infect several subsets of T lymphocytes, possibly including immature cells or that these cells can undergo phenotypic modulation.

Infection and transformation of fresh human umbilical cord blood cells by multiple sources of human T-cell leukemia-lymphoma virus (HTLV).

Human T-cell leukemia-lymphoma virus (HTLV) was first isolated from sporadic patients with adult T-cell malignancies in the United States and subsequently from T-lymphocytes established in culture from additional T-cell leukemia-lymphoma patients living in different geographical areas of the world. Co-cultivation of normal umbilical cord blood with lethally irradiated, HTLV-positive lymphocytes established in culture from many of these patients resulted in the productive infection of the cord blood T-lymphocytes which grew in suspension culture in the absence of exogenous TCGF. These transformed cord blood cells have morphological and cytochemical properties similar to HTLV-positive fresh and cultured tumor T-cells and are distinguishable from virus donor cells by HLA haplotype and chromosomal markers. These cells express HTLV proteins, release type-C virus particles and contain surface receptors for TCGF. These results demonstrate that HTLV isolated from T-cell leukemic donors from different parts of the world can productively infect and transform fresh human cord blood T-lymphocytes, and that the transformed cells share many similarities with fresh or cultured leukemic cells.