C. C. K. Lam

Post-transplantation lymphoproliferative disease of natural killer cell lineage: a clinicopathological and molecular analysis.

Post‐transplantation lymphoproliferative disorders (PTLD) occur after solid organ and bone marrow transplantation. They are predominantly of B‐cell and occasionally of T‐cell lineage. We report a case of PTLD of natural killer (NK) cell lineage. A renal allograft recipient developed progressive pancytopenia 1 year after transplantation. Serial bone marrow biopsies showed an increasing infiltration by large granular lymphoid cells. A subsequent leukaemic phase also developed with systemic infiltration of other organs. Immunophenotyping showed that these cells were CD2+, CD3−, CD3ε+, CD56+, CD94+, CD158a− and CD158b−. In situ hybridization showed Epstein‐Barr virus (EBV) infection of the neoplastic cells. Genotypical analysis showed the T‐cell receptor gene in germline configuration and clonal EBV episomal integration. The overall features were consistent with NK cell lymphoma/leukaemia. The patient did not respond to cessation of immunosuppression or anti‐EBV treatment. Combination chemotherapy was given, but the patient died ultimately of disseminated fungal infection. In conclusion, we have demonstrated that NK cell lymphoma is another rare type of PTLD that appears to be highly aggressive and therefore may require early chemotherapy to improve treatment outcome.

Fludarabine, mitoxantrone and dexamethasone in the treatment of indolent B- and T-cell lymphoid malignancies in Chinese patients

The treatment results of indolent lymphoid malignancies in Chinese are poorly reported. The efficacy of FND (fludarabine 25 mg/m2/d, ×3; mitoxantrone 10 mg/m2/d, ×1; dexamethasone 20 mg/d, ×5; monthly cycles, ×6) in 95 Chinese patients with indolent B‐cell malignancies (at diagnosis: 55, relapse/refractory disease: 40) and nine Chinese patients with T‐cell large granular lymphocyte leukaemia (T‐LGL leukaemia) (at diagnosis: two, refractory disease: seven) was evaluated. For B‐cell malignancies, the complete response (CR), partial response (PR) and overall response (OR) rates were 50·5%, 18% and 68·5% respectively. Better results were obtained for primary versus relapse/refractory disease (CR: 60% vs. 37·5%, P = 0·03; OR: 84% vs. 47·5%, P < 0·001; median progression‐free survival (PFS): 44 months vs. 22 months; 2‐year PFS: 66% vs. 47%, P = 0·039; overall survival (OS): not reached vs. 32%; 2‐year OS: 92% vs. 58%, P < 0·001). Responsive patients (CR/PR) had a better median PFS (44 months vs. 5 months, P < 0·001) and OS (67 months vs. 13 months, P < 0·001) than unresponsive patients. For T‐LGL leukaemia, the CR and molecular‐remission rates were 56% and 67% (median follow‐up: 23 months). FND is an active regimen for the treatment of indolent B‐ and T‐cell malignancies in Chinese patients, with results comparable with Western patients with similar indolent lymphomas.

T-Cell Large Granular Lymphocyte Leukemia of Donor Origin After Allogeneic Bone Marrow Transplantation

A 39-year-old man with chronic myeloid leukemia in accelerated phase underwent allogeneic bone marrow transplantation (BMT). At 6 months after BMT, lymphocytosis (WBC count, 23,100/microL [23.1 x 10(9)/L]; 80% (0.80) large granular lymphocytes [LGLs]) occurred. The LGLs were CD3+CD4-CD8+, with clonally rearranged T-cell receptor gamma gene, and of donor origin, as shown by analysis of polymorphic microsatellite markers. Epstein-Barr virus was not present. The diagnosis, therefore, was consistent with T-cell large granular lymphocytic (T-LGL) leukemia. Corticosteroids controlled the LGL count, but progressive pancytopenia led to death 4 months later. Retrospective analysis showed that the T-LGL leukemia apparently had arisen as early as 3 months after BMT. The distinguishing features of this case included donor origin, neoplastic nature, and the aggressive fatal outcome.

Successful treatment of acquired factor VIII inhibitor with cyclosporin

Summary.  Acquired factor VIII inhibitor causes a rare but life‐threatening form of bleeding disorder, owing to the formation of auto‐antibodies against FVIII. Treatment modalities include the use of immunosuppressive drugs such as cyclophosphamide and corticosteroids, plasmapheresis and i.v. immunoglobulin. A patient with idiopathic acquired FVIII inhibitor presented with serious bleeding complications resistant to all the above therapeutic modalities. Treatment with cyclosporin, however, resulted in a prompt and complete response. The lack of side‐effects and the relatively quick response suggest that cyclosporin may be tried as front line treatment for patients with acquired FVIII inhibitors.

Near Tetraploidy in Three Cases of Acute Myeloid Leukemia Associated with Mediastinal Granulocytic Sarcoma

Granulocytic sarcoma (GS) is a rare manifestation of acute myeloid leukemia (AML), blastic transformation of chronic myeloid leukemia, and the myelodysplastic syndromes. The mediastinum is an unusual site of presentation. We report a series of three female patients with mediastinal GS. They were characterized by the presence of large and bizarre blast cells and near tetraploidy on cytogenetic analysis. All three patients responded poorly to chemotherapy. Near tetraploid AML is a rare entity, usually present in male patients, and has not been associated with GS. The clinical and pathological similarities in these three cases suggest a distinct category of poor-risk AML for which more intensive treatment is needed.

Peripheral γδ T-cell deficit in nasopharyngeal carcinoma

Previous studies identified CD56+ and CD56− subsets of peripheral γδ T cells from healthy donors. Both subsets responded to stimulation by a myeloma cell line, XG‐7 and undergo vigorous ex vivo expansion in the presence of exogenous IL‐2. They are cytotoxic for different tumor targets including nasopharyngeal carcinoma, but they differ from one another in that the CD56− subset has an additional growth requirement for IL‐7 and exhibited greater cytotoxicity against nasopharyngeal carcinoma (NPC) targets. These immune cells were further shown to retard tumor growth in a nude mice NPC model. To assess if these immune cells might contribute to host defense against NPC, we compared γδ T‐cell status of NPC patients with healthy donors and survivors who had been in clinical remission of the cancer. It was found that peripheral γδ T cells of patients were impaired in their response to the stimulatory effects of XG‐7 and exhibited weak or essentially no cytotoxicity for the NPC targets. The deficits were present in early and advanced stages of the cancer but were restored among survivors after successful treatment of the cancer. These findings support a role for peripheral γδ T cells in host defense against NPC. It was noted that these immune cells comprise less than 5% of peripheral blood monocytic cells and hence it was not surprising that this component of host defense was breached early in the development of the cancer.

Fludarabine, mitoxantrone and dexamethasone as first-line treatment for T-cell large granular lymphocyte leukemia

Fludarabine, mitoxantrone and dexamethasone as first-line treatment for T-cell large granular lymphocyte leukemia

Granulocytic sarcoma of megakaryoblastic differentiation complicating chronic idiopathic myelofibrosis

We report the development of soft tissue granulocytic sarcoma with megakaryoblastic differentiation in a patient with chronic idiopathic myelofibrosis, which has hitherto been undescribed. Although an artifactual signet ring appearance of the blasts was found in the formalin-fixed tissue and caused diagnostic problems, the histological appearance on B-5 fixed material and immunophenotyping confirmed the diagnosis. Cytogenetic analysis showed 47,XY,+der(1)del(1)(?p13) at initial presentation and 47,XY,del(1)(?13),+der(1)del(1)(?p13) at the time of soft tissue blastic transformation, indicating that partial trisomy 1 might be of pathogenetic significance.

Cytogenetic triclonality in acute myeloid leukemia: A morphologic, immunologic and in situ hybridization study

Cytogenetically unrelated clones are uncommon in hematologic malignancies. We report a case of acute myeloid leukemia, which consisted morphologically of two populations of small and large blasts demonstrating immunophenotypic heterogeneity. Cytogenetic analysis showed 3 karyotypically abnormal clones: 47,XY, +14/45,XY,dic(5;17)(q11;p11),14dmin, and a near-tetraploid clone. In situ hybridization showed that the near-tetraploid clone corresponded to the large blasts, and the near-diploid clones the small blasts, therefore demonstrating a direct relationship between cell size and DNA content. The diverse morphologic, immunologic and cytogenetic heterogeneity observed in our case suggested hematopoietic oligoclonality.

Trisomy 8 as a secondary genetic change in acute megakaryoblastic leukemia associated with Down's syndrome.

Trisomy 8 as a secondary genetic change in acute megakaryoblastic leukemia associated with Down’s syndrome