Neurolymphomatosis of the median nerve, optic nerve, L4 spinal nerve root and cauda equina in patients with B-cell malignancies: a case series.

BACKGROUND: Neurolymphomatosis is rare. Neoplastic lymphocytes are seen to invade nerves (cranial or peripheral), nerve roots or other related structures in patients with hematological malignancy. It is a separate entity from central nervous system lymphoma. Neurolymphomatosis has most commonly been described in association with B-cell non-Hodgkin lymphoma. Neurolymphomatosis in the context of Burkitt lymphoma and the post-renal transplant setting has not been described before. CASE REPORTS: We report for the first time in the Arabian Gulf countries and nearby Arab states four cases of neurolymphomatosis (one Asian, and the other 3 are from Arabic nationals) occurring between 2012 and 2017 involving the median nerve, optic nerve, nerve root and cauda equina in patients with Burkitt lymphoma, Philadelphia chromosome-positive B-cell acute lymphoblastic leukemia and diffuse large B-cell lymphoma. CONCLUSIONS: Neurolymphomatosis is rare and can be difficult to diagnose by biopsy but reliably confirmed by a combined imaging approach. Prior treatment with high-dose dexamethasone might suppress 18F-fluorodeoxyglucose (FDG) activity and decrease the sensitivity of positron emission tomography/computed tomography (PET/CT). The prognosis is generally poor but using high-dose methotrexate as well as high-dose chemotherapy and autologous stem cell transplantation may be an effective way to treat neurolymphomatosis.

Chronic lymphocytic leukaemia cells become both activated and immunosuppressive following interaction with CD3 and CD28 stimulated PBMC.

Chronic lymphocytic leukaemia (CLL) is associated with immunosuppression. The activation of CLL cells induced by interaction with other cell types, particularly activated T-cells, within the tumour micro-environment is thought to be important for CLL progression. However it is unclear whether activated CLL cells (CLL(Act)) have immunosuppressive capacity. We report that co-culture of CLL cells with normal PBMC in the context of CD3/CD28 T-cell activation generates CLL(Act) with increased CD38 expression that are capable of suppressing the proliferative responses of both CD4+ and CD8+ T-cells. The suppression required cell contact but did not involve induction of T-cell apoptosis.

Survival of myeloma patients following the introduction of thalidomide as a second-line therapy: a retrospective study at a single New Zealand centre.

AIM: This retrospective study compares the overall survival (OS) of multiple myeloma (MM) patients following treatment at a New Zealand hospital over a period in which novel therapies were available but restricted, almost exclusively, to thalidomide as a second-line therapy. METHODS: Clinical, laboratory and OS data were collected on 361 MM patients who were treated at Christchurch Hospital during 2000-2010. Patients were subdivided according to the clinical criteria used to determine front-line treatment decisions. Older patients (age ≥66, n = 180) generally received standard-dose chemotherapy without autologous stem cell transplant (SCT) and formed one group. Younger patients were further subdivided according to whether they received autologous SCT (n = 89), allogeneic SCT (n = 24) or no SCT (n = 68). RESULTS: Older patients had a significantly shorter OS (P < 0.0001) than younger patients (median OS = 25 vs 78 months) however treated. Analysis of relative survival demonstrated that the increased mortality of older patients was greater than that attributable to normal ageing. Younger patients who received no transplant had a significantly shorter OS (P < 0.0001) than those who received autologous SCT or allogeneic SCT with 5-year survivals of 38%, 70% and 72% respectively. Use of novel therapies was significantly higher in younger than older patients (60% vs 47%, P = 0.011). CONCLUSIONS: The front-line treatment groupings of hospital MM patients had significantly different survivals. The OS of SCT ineligible patients remains poor despite the introduction of thalidomide.

Relative recovery of haematopoietic stem cell products after cryogenic storage of up to 19 years.

There is an increasing trend towards long-term frozen storage of haematopoietic stem cells. For such stem cells, harvested from peripheral blood (PB) or BM, it is not known if stem cell viability decreases with time. In this study, 31 separate bags of stem cell product (SCP) stored for 11-19 years (median 15 years) were assessed for total nucleated cell (TNC) count, colony forming unit-granulocyte/macrophage (CFU-GM), CD34⁺ cell count and cell viability. The results were compared with the initial results obtained for the products at the time of stem cell harvest, and the percentage recovery of each parameter was plotted against time. Recovery of TNC, CD34⁺ cell count and cell viability decreased with time (P=<0.01) but CFU-GM did not. This study shows that SCPs harvested from PB and BM do deteriorate with long-term storage. This could have an impact on rates of engraftment.

CD38 as a prognostic marker in chronic lymphocytic leukaemia at a single New Zealand centre: patient survival in comparison to age- and sex-matched population data.

AIM: The aim of this study is to determine whether the analysis of CD38 expression by chronic lymphocytic leukaemia (CLL) cells provides useful additional prognostic information. METHODS: Clinical, laboratory, overall survival (OS) and treatment-free survival (TFS) data were collected on 130 CLL patients who had CD38 expression analysed at Canterbury Health Laboratories, New Zealand (NZ) during 1998-2008. RESULTS: The detection of any level of CD38 expression by CLL cells was associated with a significantly shorter OS and TFS. When analysis was restricted to Binet stage A patients, CD38 expression identified a subset of patients (21%) who, in common with Binet stage B/C patients, had a significantly shorter OS and TFS (P<0.0015), and a TFS at 4 years of <10%. In contrast, CD38-negative Binet stage A patients had an OS that was not significantly different from that of an age/sex-matched NZ population and a 5-year TFS of 77%. CONCLUSION: This study indicates that, when combined with clinical staging, the presence of any detectable CD38 expression can be used to further improve the identification of CLL patients with more aggressive disease (i.e. Binet stage B/C or Binet stage A and CD38 positive). This will allow better identification of those patients requiring more intensive monitoring and also allow improved patient counselling regarding prognosis.

Release and clinical significance of soluble CD83 in chronic lymphocytic leukemia.

Soluble CD83 (sCD83), a potent immunosuppressive agent, circulates at elevated levels in some chronic lymphocytic leukemia (CLL) patients. We report that CLL patients with elevated plasma sCD83 levels had significantly shorter (P=0.038) treatment free survival. Culture of CLL cells with solid phase CD83 mAb+IL-4 significantly increases sCD83 release (23-117-fold, P=0.013) and ligation of normal donor PBMC with solid phase CD83 mAb alone induces similar significant increases in sCD83 release (P=0.003). RT-PCR analysis detected the presence of a transcript for sCD83 in 2/3 CLL samples. These results suggest sCD83 release may play a regulatory role in CLL progression.