Early-stage diffuse large B cell lymphoma of the head and neck: clinico-biological characterization and 18 year follow-up of 488 patients (IELSG 23 study).

It is known that extranodal head and neck diffuse large B cell lymphomas (eHN-DLBCL) can affect various anatomical structures what is not well-known, however, is whether they differ in terms of clinical presentation and outcome. Clinical data of the multi-institutional series, the largest of its kind as yet, has been analysed with the aim of answering these open questions and providing long-term follow-up information. Data from 488 patients affected by stage I/II eHN-DLBCL was collected: 300 of the Waldeyer's Ring (WR), 38 of the parotid and salivary glands (PSG), 48 of the thyroid gland (TG), 53 of the nasal cavity and paranasal sinuses (NPS), 24 of the palate and oral cavity (POC) and 25 with more than one involved site. Different eHN-DLBCL arising have distinct characteristics at presentation. The intermediate high risk-modified IPI was 67 % in TG, 44 % in WR, 38 % in PSG and POC and 20 % in MS. The worst 5-year survival rate had TG-DLBCL (61 %) due to the 61 % of patients with a mIPI >1. The addition of radiotherapy (cRT) to remitters did not translate into a survival advantage (5-year disease-free survival of 67 % in the cRT group vs. 70 % in the other). Three of four central nervous system recurrences occurred in NPS-DLBCL. Survival of HN-DLBCL was inferior to nodal DLBCL. This study showed that eHN-DLBCL remitters have an inferior survival when compared to nodal DLBCL, and that the addition of cRT does not provide a survival advantage. Since the standard of care nowadays is chemo-immunotherapy, survival of these patients might have been improved.

Transient myeloproliferative disorder with a CD7+ and CD56+ myeloid/natural killer cell precursor phenotype in a newborn.

Anewborn with a transient myeloproliferative disorder and a myeloid/natural killer cell leukemia phenotype is described. The blasts expressed CD7, CD33, CD34, CD56, and CD117 but did not react with cytoplasmic myeloperoxidase and were negative for cy CD22, HLA-DR, and CD90 expression. No megakaryoblastic surface markers were identified. The blast population disappeared from the peripheral blood and bone marrow within 2 months, but hepatomegaly and recurrent respiratory insufficiency persisted. The patient died of unilateral pneumonia in the third month of life. Neither extramedullary infiltration nor other hematologic signs of disease progression were found.

Procalcitonin-reduced sensitivity and specificity in heavily leucopenic and immunosuppressed patients.

Procalcitonin (PCT) has proven to be a very sensitive marker of sepsis for non-leucopenic patients. Little is known about its relevance in immunosuppressed and leucopenic adults. Four hundred and seventy-five PCT determinations were carried out in 73 haematological patients: on 221 occasions the white blood cell (WBC) count was < 1.0 x 10(9)/l and on 239 occasions it was > 1.0 x 10(9)/l leucocytes. Patients were classified as: non-systemic infected controls (n = 280), patients with bacteraemia (n = 32), sepsis (n = 30), severe sepsis (n = 3), septic shock (n = 3) and systemic inflammatory response syndrome (SIRS) (n = 62). When the WBC count was > 1.0 x 10(9)/l, gram-negative bacteria induced higher PCT levels (median 9.4 ng/ml) than gram-positives (median 1.4 ng/ml). In cases with a WBC < 1.0 x 10(9)/l, PCT levels were similar for gram-negative and gram-positive bacteria (1.1 ng/ml versus 0.85 ng/ml). Regardless of the leucocyte count, the median PCT level in bacteraemia cases always remained < 0.5 ng/ml. In heavily leucopenic situations, PCT levels were never > 2 ng/ml even in the sepsis and severe sepsis/septic shock groups, whereas a WBC count > 1.0 x 10(9)/l resulted in median PCT values of 4.1 ng/ml and 45 ng/ml respectively. The positive predictive value for sepsis (cut-off 2 ng/ml) was 93% in cases of WBC count > 1.0 x 10(9)/l, but only 66% in leucopenic conditions. The negative predictive value (cut-off 0.5 ng/ml) was 90% when the WBC count was > 1.0 x 10(9)/l and 63% in leucopenic conditions. Procalcitonin is an excellent sepsis marker with a high positive- and negative-predictive value in patients with WBC count > 1.0 x 10(9)/l, but it does not work satisfactorily below this leucocyte count.

Technetium-99m-sestamibi scintigraphy: an alternative approach for diagnosis and follow-up of active myeloma lesions after high-dose chemotherapy and autologous stem cell transplantation.

Technetium-99m-sestamibi (MIBI) is a radionuclide tracer taken up by different malignant tumors. A total of 88 MIBI scans were carried out in 20 individuals with monoclonal gammopathy of unknown significance (MGUS) and 10 patients during follow-up for other cancers. Of these 58 MIBI scans were carried out in 46 myeloma patients: 15 at diagnosis, 14 during conventional chemotherapy, and 29 following high-dose sequential therapy and autologous peripheral blood progenitor support. A positive MIBI scan was exhibited by lof 10 with non-myeloma cancers and 2 of 20 with MGUS. In contrast, all stage II and III multiple myelomas (MM) were positive at diagnosis. Therefore, the sensitivity of the MIBI scan at diagnosis was 100%, whereas the specificity in this cohort was 93%. Four different MIBI patterns could be distinguished in MM patients: physiological, focal, diffuse, and extramedullary uptakes. In comparison to conventional skeletal radiographs, MIBI scans recognized a higher number of myeloma lesions at diagnosis. MIBI scans remained positive in all patients during conventional chemotherapy, and there was a direct correlation between MIBI result and clinical outcome of patients following high-dose therapy. Eighteen patients had a negative MIBI scan: 9 were in complete remission (CR), 8 in partial remission (PR), and 1 had progressive disease. Eleven patients showed lesions on the MIBI scan: 4 were in PR, 5 had progressive disease, 1 had a minimal response, and only 1 was in CR. A diffuse MIBI pattern reflected a higher bone marrow plasma cell number. In five patients, histologically or cytologically verified soft tissue myeloma lesions were correctly diagnosed by MIBI scan, while all plain radiographs showed none of them. MIBI has proven to be an effective tool in diagnosing biologically active myeloma.

Peripheral blood monoclonal B-cells predict the event free survival in multiple myeloma.

Reinfusion of myeloma progenitor cells may contribute to relapse of multiple myeloma after autologous stem cell transplantation. The aim of our study was to investigate whether monoclonal B-cells are present in the apheresis product and to evaluate the clinical relevance of these cells. Leukapheresis products of 55 patients were purged with anti-B-cell-Monoclonal antibodies (MoAbs) and immunobeads. Monoclonal B-cells were found in 85% of patients within the B-cell population. In one third of all myeloma patients, the majority of B-cells was represented by monoclonal myeloma progenitor B-cells, whereas in two thirds of patients monoclonal cells only represented a small part of the entire B-cell population. As shown by sequence analysis, monoclonal precursor B-cells and malignant plasma cells had the identical genetic CDR III sequence. The purging efficacy, using a negative selection system, was a median of 3 logs (range 1,5-3,5). No statistical difference in the purging efficacy was found when 3, 4 or 5 MoAbs against B-cells antigens were used. However, a tumor specific signal could be detected in the purged harvest of all patients, when the highly sensitive ASO-PCR approach was used. Furthermore, we found a direct correlation between the amount of remaining monoclonal cells after negative selection and the event free survival of myeloma patients. 10/15 patients with a median of 20 x 10(3) monoclonal cells in the purged product relapsed at a median of 1,4 years, whereas only 6/24 patients with an oligoclonal pattern including a low number of remaining monoclonal cells relapsed at a median of 2,2 years. The event free survival (EFS) was statistically different between the two groups (p = 0,014).