Recurrent finding of the FIP1L1-PDGFRA fusion gene in eosinophilia-associated acute myeloid leukemia and lymphoblastic T-cell lymphoma.

The FIP1L1-PDGFRA fusion gene has been described in patients with eosinophilia-associated myeloproliferative disorders (Eos-MPD). Here, we report on seven FIP1L1-PDGFRA-positive patients who presented with acute myeloid leukemia (AML, n=5) or lymphoblastic T-cell non-Hodgkin-lymphoma (n=2) in conjunction with AML or Eos-MPD. All patients were male, the median age was 58 years (range, 40-66). AML patients were negative for common mutations of FLT3, NRAS, NPM1, KIT, MLL and JAK2; one patient revealed a splice mutation of RUNX1 exon 7. Patients were treated with imatinib (100 mg, n=5; 400 mg, n=2) either as monotherapy (n=2), as maintenance treatment after intensive chemotherapy (n=3) or in overt relapse 43 and 72 months, respectively, after primary diagnosis and treatment of FIP1L1-PDGFRA-positive disease (n=2). All patients are alive, disease-free and in complete hematologic and complete molecular remission after a median time of 20 months (range, 9-36) on imatinib. The median time to achievement of complete molecular remission was 6 months (range, 1-14). We conclude that all eosinophilia-associated hematological malignancies should be screened for the presence of the FIP1L1-PDGFRA fusion gene as they are excellent candidates for treatment with tyrosine kinase inhibitors even if they present with an aggressive phenotype such as AML.

Donor lymphocyte infusion enhances remission status in patients with persistent disease after allografting for multiple myeloma.

Two patients with persistent disease after allografting for multiple myeloma received donor T-cell lymphocyte infusion (DLI) (1.5 x 10(8) and 7 x 10(7)) to induce a graft-vs.-myeloma effect for further tumour regression after withdrawal of immunosuppression. The interval between stem cell transplantation and DLI was 8 and 14 months respectively. Both patients converted from partial to complete remission, lasting 12+ and 28+ months. Immunofixation became negative after 3 and 4 months. The main toxicity was grade II and III acute graft-vs.-host disease (GvHD) and limited or extensive chronic GvHD in each patient. We conclude that DLI induced further tumour reduction in patients with persistent disease after allografting for multiple myeloma.

Properties of cutaneous mechanosensitive afferents during the early stages of regeneration in man.

The technique of percutaneous microneurography was used to record single unit activity from 75 regenerated primary afferents innervating the glabrous skin of the human hand. Thirteen patients were studied, who had suffered complete transection, with subsequent suture or graft, of the median or ulnar nerves. The recordings were obtained from 7 to 23 months postoperatively (early regeneration). Three types of mechanoreceptive afferents (RA, SAI, SAII) and many deep units of unknown origin were found. No regenerated PC units could be identified. The reinnervated receptors were predominantly located in the palm and proximal fingers, comparable to those found 3 years or more postoperatively (late regeneration). Response thresholds and in general, discharge and receptive field characteristics of the majority of afferents were largely comparable to late regeneration and normal. The properties of SAII units were like normal in all respects. However, several distinct abnormalities were encountered early during regeneration: multiple receptive fields innervated by a single afferent (2/9 RA and 2/9 SAI), unusually small or large receptive fields (RA and SAI), pronounced fatigue on repetitive stimulation (7/15 SAI, 4/6 deep). Responses of reinnervated skin to sustained and repeated indentations were found to be similar to those of normal skin, and therefore, could not account for the abnormal discharge behavior. It is suggested that the transitional properties of regenerating afferents reflect unstable axon-end organ connections and immature axonal properties. Both factors would contribute to the slow course of sensory recovery, making prognosis on tactile recovery unpredictable.

Transitional properties of afferents reinnervating mechanoreceptors in the human glabrous skin.

The technique of percutaneous microneurography was used to record in man from single mechanoreceptive afferents during the early stages of reinnervation. Although response properties were in several ways comparable to normal and to those of afferents studied long after nerve repair, two abnormalities were found: multiple receptive field innervation by single afferents (RA, SAI), and response fatigue with repeated stimulation (SAI). These abnormalities are considered transitional, disappearing when reinnervation is complete.