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Editorials
prior work, that the molecular pathogenesis of the CD4+ References
and CD8+ cases of ITLPD-GIT appears distinct.10,23 Thus, more formal separation of these phenotypic variants may be warranted in the future.
The current series presents both similarities with and differences from prior clinical reports.12 Endoscopic find- ings included multiple mucosal lesions, often with nodu- larity or polyps. Only one case was associated with mucosal ulceration. Most of the patients had a very pro- tracted clinical course, with two patients being alive 19 and 21 years after diagnosis. There is a small but signifi- cant risk of transformation, with disease progressing in two patients after 11 and 27 years of follow-up. A vari- ety of treatments were employed, with no patient stated to attain a complete remission.
In prior series, all patients had disease confined to the gastrointestinal tract, with extraintestinal dissemination seen only in patients with histological progression.9,10 However, Soderquist et al. report bone marrow involve- ment in three cases, all of which were detected prior to transformation. In one case bone marrow involvement was detected only through an unidentified cytogenetic abnormality; the bone marrow was morphologically nor- mal and lacked evidence of a monoclonal T-cell receptor gene rearrangement. This patient is alive with disease at 7 years after presentation, so the presence of bone mar- row involvement, if real, has had little clinical impact. Two additional patients were reported to have inguinal lymph node involvement, one of whom also had positive bone marrow. This latter case is the only patient classified as having Ann Arbor Stage IV disease. This 41-year old male was asymptomatic at presentation, and is untreated, being alive with disease at 1 year. Curiously, the remain- ing three patients said to have “biopsy-proven” involve- ment of lymph node or bone marrow were classified as stage IE at diagnosis. Presumably, the stated bone mar- row or lymph node involvement occurred at some later point during the clinical course. More data are needed to understand the clinical and biological significance of this extraintestinal dissemination, including molecular data to confirm involvement.
A remaining issue is the optimal therapy for ITLPD- GIT. Most of the data are anecdotal. A number of patients have been treated with a variety of chemotherapy regi- mens used in both B-cell and T-cell lymphomas.9 Most patients have failed to achieve any long-term benefit from conventional chemotherapy. The JAK-STAT path- way appears to be an attractive target, especially in patients with CD4+ disease, and in recent years there has been interest in the use of targeted agents for a variety of mature T-cell and NK-cell malignancies.24 Ruxolitinib is a JAK-inhibitor approved for use in myeloproliferative neo- plasms, and has shown some activity in cutaneous T-cell lymphomas with activation of the JAK-STAT pathway.24 Other agents under evaluation for T-cell and NK-cell lym- phomas include tofacitinib, pacritinib, and the histone deacetylase inhibitor, chidamide. The use of targeted agents in combination with either chemotherapy or immunotherapy may offer promise in the future.
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haematologica | 2020; 105(7)