The clinical, laboratory, and survival characteristics of our RS patients were similar to those reported in earlier studies. Ig gene rearrangement and light-chain isotype analysis support a common origin for CLL and LCL. Despite progress in the treatment of CLL, the development of LCL remains a serious complication and continued surveillance in all CLL patients is warranted.

Donor lymphocyte infusions can reinduce complete remission in the majority of patients with chronic myelogenous leukemia (CML) who relapse into chronic phase after allogeneic bone marrow transplantation (BMT). Such infusions are associated with a high incidence of graft- versus-host disease (GVHD) and marrow aplasia. BMT using selective depletion of CD8+ lymphocytes from donor cells reduces the incidence of GVHD without an increase in leukemia relapse. We hypothesized that infusion of CD8-depleted donor peripheral blood lymphocytes could also reinduce complete remissions with a lesser potential to produce symptomatic GVHD in patients with CML who relapsed after allogeneic BMT. Ten patients with Ph(+) CML who relapsed a median of 353 days after BMT (range, 82 to 1,096 days) received donor lymphocyte infusions depleted of CD8+ cells. Nine patients received a single infusion and 1 received two infusions. Four patients were treated while in chronic phase with clonal evolution, 2 during accelerated phase, 3 during blast crisis, and 1 in a cytogenetic relapse. A mean of 0.9 +/- 0.3 x 10(8) mononuclear cells/kg were infused, containing 0.6 +/- 0.4 x 10(6) CD3+CD8+ cells/kg. Six patients achieved hematologic and cytogenetic remission at 4, 8, 11, 15, 39, and 54 weeks after lymphocyte infusion. Two patients developed > or = grade II acute GVHD, and 1 patient developed mild chronic GVHD. We conclude that donor lymphocyte infusions depleted of CD8+ cells can induce remissions with a low rate of severe acute GVHD in patients with CML who relapse after allogeneic BMT, supporting the hypothesis that CD8+ lymphocytes are important effectors of GVHD, but may not be essential for the graft-versus- leukemia effect against this disease. Further controlled studies are required to confirm these preliminary observations.

Acute promyelocytic leukemia (APL) is characterized by fusion of RARA with PML, or rarely other gene partners. We report a patient with APL with a novel fusion between RARA and the interferon regulatory factor 2 binding protein 2 (IRF2BP2) genes. A 19-year-old woman presented with ecchymoses and epistaxis. Bone marrow examination showed morphologic and immunophenotypic features consistent with APL. PML oncogenic domain antibody was positive. Conventional cytogenetics, FISH, RT-PCR and oligonucleotide microarray for PML-RARA and common APL variant translocations were negative. Next generation RNAseq analysis followed by RT-PCR and direct sequencing revealed distinct breakpoints within IRF2BP2 exon 2 and RARA intron 2. The patient received ATRA, arsenic trioxide and gemtuzumab ozogamicin, and achieved complete molecular remission. However, the disease relapsed ten months later, two months after completion of consolidation therapy. This case expands the list of novel RARA partners identified in APL.

Filgrastim may be effective in selected cases of leukemic relapse after allogeneic bone marrow transplantation.

Fine-needle aspiration (FNA) cytology of lymph nodes in malignant lymphoma is fraught with difficulty. In certain clinical situations, cytology has been documented to be useful in patients with malignant lymphoma. The intent of our investigation was to determine the accuracy of a multiparameter approach in diagnosing lymphoma. We reviewed the results of FNA cytology combined with the immunocytochemistry and, in some cases, the Southern blots of aspirated cell suspensions obtained from 86 suspected lymphoma patients who subsequently underwent surgical biopsy of the aspirated site. In four cases, in which FNA was unable to retrieve sufficient material for diagnosis, the histology showed extensive fibrosis. When the FNA diagnoses were compared with the histologic diagnoses, the diagnosis concurred in 69 cases (56 malignant lymphomas, 12 reactive, 1 atypical lymphoid proliferation). There was one false-positive, six false-negatives, and eight cases diagnosed as atypical lymphoid proliferation. Overall accuracy was 91%. There were two types of false-negative cases: those in which a diagnosis of another malignancy or unspecified malignant neoplasm was made and those that were diagnosed as reactive when the histology showed lymphoma. In seven cases, the DNA rearrangement studies of the antigen receptor genes were successfully performed on the aspirated cells and were useful in establishing lineage and clonality of both B and T lymphoid cells. Our study indicated that the use of a multiparameter approach in the diagnosis of malignant lymphoma by FNA enhanced the accuracy of diagnosis of the non-Hodgkin's lymphomas. In Hodgkin's disease, no benefit was derived from the approach.