Takuji Ichihashi

Retrospective analysis of prognostic factors for angioimmunoblastic T-cell lymphoma: a multicenter cooperative study in Japan

Angioimmunoblastic T-cell lymphoma (AITL) is a major type of peripheral T-cell lymphoma (PTCL). To elucidate the clinicopathologic characteristics and prognosis of AITL in Japan, we retrospectively analyzed 207 patients with AITL. The median patient age was 67 years (range, 34-91 years), with 73% of patients older than 60 years. With a median follow-up of 42 months in surviving patients, 3-year overall survival (OS) was 54% and progression-free survival (PFS) was 38%. The International Prognostic Index (IPI) and the prognostic index for PTCL, not otherwise specified (PIT) were predictive for OS in this analysis. Multivariate analysis found that age older than 60 years, elevated white blood cell (WBC) and IgA levels, the presence of anemia and thrombocytopenia, and extranodal involvement at > 1 site were significant prognostic factors for OS, and IgA, anemia, and mediastinal lymphadenopathy were significant prognostic factors for PFS. A novel prognostic model consisting of the prognostic factors for OS was successfully constructed. In conclusion, IPI and PIT were still useful for prognostication of AITL, and other factors, including those not used in IPI, such as IgA, anemia, WBC count, thrombocytopenia, and mediastinal lymphadenopathy, also significantly affected prognosis. Future investigations for IgA as a unique prognostic factor are warranted.

A novel myeloid cell line, Marimo, derived from therapy-related acute myeloid leukemia during treatment of essential thrombocythemia: Consistent chromosomal abnormalities and temporary C-MYC gene amplification

A novel myeloid leukemia cell line, Marimo, was established from bone marrow cells of a patient with secondary acute myeloid leukemia (AML) that had developed during the treatment of essential thrombocythemia (ET) with busulfan. Karyotype at the ET phase was 46,XX,der(15)t(1;15) (q23;p12-13), but at the blastic phase changed to 44,XX,-5,del(8)(q22), add(17)(p11),+18, psu dic(18;9) (q23;p21) x 2 lacking t(1;15). In Marimo cells, C-MYC gene was temporarily amplified by double-minutes (dmin) but disappeared at 33 months, whereas t(10;14;11)(q22;q32;q13) and t(10;14)(q22;q32) were added in vitro psu dic(18;9) x 2 and add(17)(p11) were consistently found throughout the culture. These results suggest that this AML clone is not derived from ET but rather is therapy-related.

Clinical characteristics and outcomes in patients with t(8;21) acute myeloid leukemia in Japan

Clinical characteristics and outcomes in patients with t(8;21) acute myeloid leukemia in Japan

Effective treatment of adult T cell leukemia/lymphoma with a novel oral antitumor agent, MST-16.

Adult T cell leukemia/lymphoma (ATLL) induced by human T cell leukemia virus I is resistant to conventional therapy. Six patients with ATLL were treated with a new antitumor agent, MST-16, which is a derivative of bis(2,6-dioxopiperazine). Two patients achieved complete remission, lasting 12 months and more than 8 months, and 2 others partial remission, lasting 2 months and 6 weeks, respectively. The major toxicity was myelosuppression. Other toxicities were not severe and were well tolerable. Orally administered MST-16 is a promising agent for the treatment of ATLL.

Clinical significance of minimal residual disease in patients with t(8;21) acute myeloid leukemia in Japan

To examine the prognostic significance of minimal residual disease (MRD) in t(8;21) acute myeloid leukemia (AML), 96 bone marrow samples from 26 Japanese patients in complete remission (CR) were analyzed regarding the RUNX1/MTG8 transcript using real-time reverse transcriptase polymerase chain reaction assay. All patients were treated with intensive chemotherapy. The median copy number of the RUNX1/MTG8 transcript, measured after each treatment course decreased over time. However, an increase in the MRD level was documented in three patients after the second consolidation, and all of them subsequently relapsed. The relapse-free survival (RFS) did not differ between the patients whose MRD levels were below or above 1,000 copies/µg after the first consolidation, with respective 2-year rates of 62 and 86% (P = 0.21). With respect to the MRD level after induction therapy, our data also failed to show any favorable effect of a lower MRD on RFS. Although these findings need to be confirmed with a larger number of patients, our data indicate that the MRD level at a given time during the early course in CR does not predict the outcome in Japanese patients.

Unusual feature of the T-cell receptor genes in T-lineage acute lymphoblastic leukemia

We characterized the T-cell receptor (TCR) gene rearrangements and sequences in 15 T-lineage acute lymphoblastic leukemia (T-ALL) and seven adult T-cell leukemia (ATL) samples. Southern blot analysis showed that neither of the two TCR delta alleles was deleted in two T-ALL samples, suggesting that the TCR alpha loci have a germ line configuration. The TCR alpha and beta sequences were cloned and sequenced by reverse transcriptase-inverse polymerase chain reaction. Two T-ALL samples had a long complementarity determining region (CDR), three of the alpha chain and the other two T-ALL samples had long CDR3 of the beta chain, compared with normal peripheral blood lymphocytes (PBL). Thus, a total of six T-ALL samples had unusual TCR gene structure, which was unrelated to the immunophenotype. On the other hand, CDR3 length in ATL samples was similar to normal PBL. These data suggest that T-ALL is derived from an immature T-cell repertoire which undergoes TCR gene rearrangement or has not been negatively selected.