Summary Hairy cell leukaemia (HCL) was first described 50 years ago. Median survival was then 4 years. The purine analogues, introduced in the 1980s, transformed this prognosis. We reviewed data retrospectively from 233 patients, treated with pentostatin (n = 188) or cladribine (n = 45), to investigate the current long‐term outlook. Median follow‐up was 16 years. There were no significant differences in outcome between the two agents. Overall, the complete response (CR) rate was 80% and median relapse‐free survival was 16 years. After relapse (n = 79) or non‐response (n = 5), 26 patients received pentostatin and 58 cladribine; 69% achieved CR and median relapse‐free survival was 11 years. After third‐line therapy (n = 23), 50% achieved CR and median relapse‐free survival was 6·5 years. However, CRs were equally durable, whether after first, second or third‐line therapy. Complete responders and those with both haemoglobin >100 g/l and platelet count >100 × 109/l before treatment had the longest relapse‐free survival (P < 0·0001). Patients still in CR at 5 years had only a 25% risk of relapse by 15 years. Outcomes for patients with recurrent disease improved with the monoclonal antibody rituximab, combined with either purine analogue. Overall only eight patients died of HCL‐related causes. Patients achieving a CR can expect a normal lifespan.

The autapomorphic status of the Neanderthal suprainiac fossa was recently confirmed. This was a result of a detailed analysis of the internal bone composition in the area of the suprainiac depression on Neanderthal and Homo sapiens specimens. However, while anatomical differences between Neanderthal suprainiac fossa and the depression in the inion region of the occipital bone of fossil and recent Homo sapiens have been discussed in detail, the etiology of these structures has not been resolved. In this article, the hypothesis that the Homo sapiens non‐supranuchal fossa and the Neanderthal suprainiac fossa both formed to maintain the optimal shape of the occipital plane (to minimize strain on the posterior cranial vault) is tested. First, the variation in the expression of the fossa above inion in the crania of recent Homo sapiens from European, African, and Australian samples was examined, and the degree of structural similarity between these depressions and the Neanderthal suprainiac fossa was assessed. Next, the relationship between the shape of the occipital squama in the midsagittal plane and two particular features (the degree of the occipital torus development and the occurrence of a depression in the inion region that is not the supranuchal fossa) were analyzed. Based on the results, it is suggested that the Homo sapiens non‐supranuchal fossa and Neanderthal suprainiac fossa are convergent traits. Am J Phys Anthropol, 2011. © 2010 Wiley‐Liss, Inc.

SummaryIn 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 < 0AE03). 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.

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) γ‐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.

BACKGROUND.The purine analogs pentostatin and cladribine have revolutionized the treatment of hairy cell leukemia (HCL) with overall responses in greater than 85% of patients and a median progression‐free survival of up to 15 years. They continue to be effective at second‐ and even third‐line therapy; however, alternative treatments are needed for patients who are or have become refractory to these agents or whose remissions are shorter with each course of therapy.METHODS.The authors conducted a retrospective review of 8 patients who received pentostatin or cladribine combined concurrently (n = 6 patients) or sequentially (n = 2 patients) with rituximab at second‐line therapy (n = 3 patients) and at subsequent lines of therapy (n = 5 patients). Results from a previously reported database of 219 patients with HCL (73 patients who received second‐line therapy and 20 patients who received third‐line therapy) were used as a historic control group against which to measure benefit.RESULTS.All 8 patients responded to therapy, with 7 complete responses (CRs) (87.5%) and minimal toxicity. All patients who had CRs were negative for minimal residual disease (MRD). At a median follow‐up of 29 months (range, 5–39 months) 1 patient developed recurrent disease, and the estimated 2‐year recurrence rate was 20% (0% after second‐line therapy and 25% after subsequent lines of therapy). In the historic control group, the CR rates were 70% after second‐line therapy and 45% after third‐line therapy, and the recurrence rates at 2 years were 15% and 33%, respectively.CONCLUSIONS.The combination of purine analogs with rituximab was safe and effective for patients with recurrent and/or refractory HCL, and the current results suggested an added benefit compared with standard treatment. Cancer 2007 © 2007 American Cancer Society.