A prospective study of chemotherapy-induced febrile neutropenia in the South West London Cancer Network. Interpretation of study results in light of NCAG/NCEPOD findings.

BACKGROUND: Chemotherapy-induced febrile neutropenia is a medical emergency complicating the treatment of many cancer patients. It is associated with considerable morbidity and mortality, as well as impacting on healthcare resources. METHODS: A prospective study of all cases of chemotherapy-induced febrile neutropenia in the South West London Cancer Network was conducted over a 4-month period. Factors including demographics, treatment history, management of febrile neutropenia and outcome were recorded. RESULTS AND CONCLUSION: Our results reflect those of the recent National Chemotherapy Advisory Group (NCEPOD, 2008)/National Confidential Enquiry into Patient Outcomes and Death reports (NCAG, 2009) and highlight the need for network-wide clinical care pathways to improve outcomes in this area.

High-grade transformation in splenic marginal zone lymphoma with circulating villous lymphocytes: the site of transformation influences response to therapy and prognosis.

In a series of 48 patients with splenic marginal zone lymphoma (SMZL) with circulating villous lymphocytes, we describe the clinical and laboratory features of nine cases that transformed to high-grade B-cell lymphoma. These patients had a significantly greater incidence of peripheral lymph node involvement at diagnosis when compared to SMZL patients who did not transform (P < 0.03). While transformation in the bone marrow is frequently refractory to therapy and associated with poor outcome in SMZL, lymph node transformation responds well to chemotherapy with durable progression-free and overall survival.

Characteristic appearances of the bone marrow in T-cell large granular lymphocyte leukaemia.

AIMS: To augment the limited literature on bone marrow (BM) appearances in T-cell large granular lymphocyte (LGL) leukaemia and to identify a histological signature to aid in diagnosis of this condition. METHODS AND RESULTS: A descriptive analysis of the histology of the BM in T-cell LGL leukaemia was performed (n = 38). Antibodies against CD3, CD4, CD5, CD8, CD16, CD56, CD57 and CD20 or CD79a were employed. Antibodies against CD68 (macrophages) and CD34 (sinusoids) were also included. BM was normocellular or hypercellular in the majority of cases, with interstitial lymphoid infiltration in 97%. Lymphoid nodules were present in 55% and intrasinusoidal permeation in 58%. Apoptotic figures and haemosiderin deposition were common. All cases showed trilinear haematopoiesis with normal or increased megakaryopoiesis and erythropoiesis, but normal/reduced myelopoiesis. Reticulin was increased (Grade II-III). Immunohistochemistry revealed interstitial infiltration in all cases and helped to identify lymphoid nodules in two-thirds of cases. Preferential localization of CD8+ T lymphocytes to the interstitium and CD4+ T lymphocytes to the periphery of CD20+ B-cell nodules was seen in almost 90% of cases. CONCLUSIONS: Nodules with non-clonal B-cell centres surrounded by CD4+ cells, with interstitial CD8+ cells, are a characteristic finding in T-cell LGL leukaemia and may represent a histological signature for this condition.

IgVH genes mutation and usage, ZAP-70 and CD38 expression provide new insights on B-cell prolymphocytic leukemia (B-PLL).

B-prolymphocytic leukemia (B-PLL) is a rare disease with poor prognosis. To further characterize the biological features of this disease, we analyzed immunoglobulin heavy chain (IgVH) mutations, ZAP-70 and CD38 in 19 cases with de novo B-PLL. Immunoglobulin heavy chain genes analysis showed an unmutated pattern (>98% homology to germ line) in 9/17 cases (53%), with 100% homology in eight. In the remaining, it ranged from 90 to 97.4%, with three cases slightly mutated (98-95%) and five heavily mutated (<95%). All B-PLL utilized members of VH3 (11/17) and VH4 (6/17) families, with V3-23, V4-59 and V4-34 gene accounting for more than half of them, regardless of mutational status. ZAP-70, assessed by flow cytometry, ranged from 1 to 91% cells, being > or =20% in 57% of cases. CD38 ranged from 1 to 99% (median 21%). There was no correlation between IgVH status and ZAP-70 or CD38 expression, but male gender and del(17p) were more common in the unmutated group. Neither IgVH mutations, CD38 expression nor del(17p) influenced patients' outcome. Unexpectedly, ZAP-70+ B-PLL patients survived longer (40 months) than ZAP-70- B-PLL (8 months). B-PLL appears biologically heterogeneous regarding IgVH mutations, ZAP-70 and CD38 expression, showing a pattern distinct from that of other lymphoproliferative disorders.

Isolated central nervous system involvement in adult T-cell lymphoma/leukaemia.

Central nervous system (CNS) presentation of adult T-cell lymphoma/leukaemia is rare, and almost invariably associated with systemic disease. We report an unusual manifestation of adult T-cell lymphoma/leukaemia, with isolated CNS involvement and unusual imaging findings. We also describe objective response to antiviral therapy. To our knowledge, this is the first report of such presentation and response.

CD52 expression in T-cell large granular lymphocyte leukemia--implications for treatment with alemtuzumab.

Few reports on the successful treatment of T-cell large granular lymphocyte (LGL) leukemia with the humanized anti-CD52 monoclonal antibody alemtuzumab are emerging in the literature. The expression of CD52 by LGLs has not been previously investigated. Using semi-quantitative 2- and 3-color flow cytometry, we documented the expression of CD52 in 100% of abnormal cells in T-cell LGL leukemia (n = 11) and natural killer (NK) cell LGL leukemia (n = 2), and showed no significant difference in CD52 expression between T-cell prolymphocytic leukemia (PLL) and T-cell LGL leukemia. Higher CD52 expression has been noted in responders to alemtuzumab in T-cell PLL and in chronic lymphocytic leukemia (CLL), a B-cell disorder. The strong and consistent expression of CD52 shown here highlights the potential role of alemtuzumab in the treatment of refractory T-cell LGL leukemia and possibly aggressive NK cell leukemia.

Prolonged treatment response in aggressive natural killer cell leukemia.

We describe a case of natural killer (NK) cell leukemia with acute presentation, systemic symptoms and hepatosplenomegaly. The uniform and aberrant phenotype of NK cells with infiltration of bone marrow and spleen was in keeping with a malignant diagnosis. Aggressive presentation was demonstrated by marked constitutional symptoms and significant tumor burden (liver, spleen, blood, bone marrow). The subsequent clinical course has been indolent, but this may have been influenced by treatment. Treatment consisted sequentially of splenectomy, intravenous pentostatin and the combination of cyclosporine A and recombinant human erythropoietin and has resulted in survival of over 48 months. We discuss the difficulties in the diagnosis of this condition, explore possible causes of cytopenia(s), and highlight the role of immunosuppression in controlling disease manifestations in large granular lymphocyte proliferative disorders.

Transformation of T-cell large granular lymphocyte leukaemia into a high-grade large T-cell lymphoma.

We describe a case of T-cell large granular lymphocyte (LGL) leukaemia that transformed into a large-cell T-cell lymphoma 11 years from diagnosis. A 29-year-old asymptomatic female presented in 1989 with lymphocytosis, neutropenia and mild bone marrow infiltration. The circulating cells were LGL with a CD2+, CD3+, CD8+, CD4-, CD16+, CD56+, CD57- phenotype. In August 2000, she developed fever, a large submandibular mass and hepatosplenomegaly. Biochemistry showed abnormal liver function tests and raised lactate dehydrogenase (LDH) levels. A serological screen for Epstein-Barr virus, cytomegalovirus, human T-lymphotropic virus-I, human herpes virus (HHV)-6 and HHV-7 was negative. Histology of the mass was consistent with the diagnosis of peripheral T-cell lymphoma composed of large cells, and immunohistochemistry showed that the lymphoma cells had a phenotype identical to the mature LGL. Molecular analysis with the polymerase chain reaction (PCR) demonstrated rearrangement of the T-cell receptor (TCR) gamma-chain gene with a band of identical size in both bone marrow mature LGL and lymph node cells. The patient was treated with CHOP (cyclophosphamide, vincristine, doxorubicin and prednisolone), resulting in the disappearance of the mass and improvement of the hepatosplenomegaly, LDH and liver abnormalities. She underwent splenectomy, and spleen histology showed involvement by T-cell LGL leukaemia with no evidence of transformation. This case illustrates that transformation or Richter syndrome may occur in a minority of patients with T-cell LGL leukaemia, a disease that has a benign clinical course in most cases. This is the first case documented by molecular methods of the transformation of the pre-existing clone.