A real-life cohort study of immunoglobulin light-chain (AL) amyloidosis patients ineligible for autologous stem cell transplantation due to severe cardiac involvement or advanced disease

Objective: To study the outcome of patients with AL amyloidosis who were ineligible for high dose melphalan (HDM) and autologous stem cell transplantation (ASCT).Methods: A real-life retrospective observational cohort study of Dutch patients with AL amyloidosis ineligible for HDM and ASCT was performed at the University Medical Center Groningen from January 2001 until April 2017. Primary outcome measure was overall survival (OS). Secondary outcome measures were hematological response (HR), organ responses, and treatment toxicity.Results: Eighty-four patients were included. Ineligibility was due to NYHA class III/IV (n = 58), otherwise advanced disease (n = 11), advanced age (n = 14), or treatment refusal (n = 1). Early death (<3 months) rate was high (44%). Median OS improved from 4 months in period 2001-2009 (n = 36) to 8 months in period 2009-2017 (n = 48, p = .02). HR was seen in 29%, and 42% of the patients, respectively. Median OS was 36 months after induction treatment with bortezomib (n = 32) and 18 months with immunomodulatory imide drug (IMID) (n = 16), both higher than median OS (7 months) with other regimens (n = 27). Incidence of toxicity was high (51%).Conclusion: OS improved in this high-risk group over the years, especially after introduction of new treatment modalities. However, early death rate remains high, illustrating the need for more effective treatment

Primary Cauda Equina T-Cell Lymphoblastic Lymphoma

BACKGROUND: T-cell lymphoblastic lymphoma (T-LBL) is a rare and aggressive form of non-Hodgkin lymphoma. This report describes, to our knowledge, the first adult case of a primary cauda equina T-LBL. Treatment consists of multiagent chemotherapy, and surgical removal of T-LBL does not improve outcome. We discuss the workup of patients with an intradural spinal mass, together with a review of the literature on primary spinal lymphoma of the cauda equina. CASE DESCRIPTION: A 54-year-old woman with Crohn's disease, for which she was taking immunosuppressive medication, presented with progressive back pain radiating to both legs and deteriorating neurologic deficits caused by an intradural, contrast-enhancing lesion in the L1-5 region. During acute surgery, the tumor was partially resected. Immunohistochemical phenotyping revealed a T-LBL. No other lymphoma localizations were found after subsequent staging. Despite extensive treatment, the patient died of disseminated disease throughout the central nervous system, 6 weeks after the diagnosis. CONCLUSIONS: Pain and progressive neurologic complaints can be symptoms of a (malignant) intradural spinal tumor. Intradural lymphoma must be considered as a differential diagnosis by clinicians because it can mimic neoplasms that often require urgent surgery. The histopathologic diagnosis should preferably be obtained by way of cerebrospinal fluid analysis or tumor biopsy because tumor resection has no beneficial effect on the oncologic outcome

Neurofilament light chain, a biomarker for polyneuropathy in systemic amyloidosis

OBJECTIVE: To study serum neurofilament light chain (sNfL) in amyloid light chain (AL) amyloidosis patients with and without polyneuropathy (PNP) and to corroborate previous observations that sNfL is increased in hereditary transthyretin-related (ATTRv) amyloidosis patients with PNP. METHODS: sNfL levels were assessed retrospectively in patients with AL amyloidosis with and without PNP (AL/PNP+ and AL/PNP-, respectively), patients with ATTRv amyloidosis and PNP (ATTRv/PNP+), asymptomatic transthyretin (TTR) gene mutation carriers (TTRv carriers) and healthy controls. Healthy controls (HC) were age- and sex-matched to both AL/PNP- (HC/AL) and TTRv carriers (HC/TTRv). The single-molecule array (Simoa) assay was used to assess sNfL levels. RESULTS: sNfL levels were increased both in 10 AL/PNP+ patients (p  I) had the highest sNfL levels compared to patients with early PNP (PND-score I) (p = .05). sNfL levels did not differ between TTRv carriers and HC/TTRv individuals. In the group comprising all healthy controls and in the group of TTRv carriers, sNfL levels correlated with age. CONCLUSION: sNfL levels are increased in patients with PNP in both AL and ATTRv amyloidosis and are related to severity of PNP in ATTRv amyloidosis. sNfL is a promising biomarker to detect PNP, not only in ATTRv but also in AL amyloidosis

LocoMMotion:a prospective, non-interventional, multinational study of real-life current standards of care in patients with relapsed and/or refractory multiple myeloma

Despite treatment advances, patients with multiple myeloma (MM) often progress through standard drug classes including proteasome inhibitors (PIs), immunomodulatory drugs (IMiDs), and anti-CD38 monoclonal antibodies (mAbs). LocoMMotion (ClinicalTrials.gov identifier: NCT04035226) is the first prospective study of real-life standard of care (SOC) in triple-class exposed (received at least a PI, IMiD, and anti-CD38 mAb) patients with relapsed/refractory MM (RRMM). Patients (N = 248; ECOG performance status of 0–1, ≥3 prior lines of therapy or double refractory to a PI and IMiD) were treated with median 4.0 (range, 1–20) cycles of SOC therapy. Overall response rate was 29.8% (95% CI: 24.2–36.0). Median progression-free survival (PFS) and median overall survival (OS) were 4.6 (95% CI: 3.9–5.6) and 12.4 months (95% CI: 10.3–NE). Treatment-emergent adverse events (TEAEs) were reported in 83.5% of patients (52.8% grade 3/4). Altogether, 107 deaths occurred, due to progressive disease (n = 74), TEAEs (n = 19), and other reasons (n = 14). The 92 varied regimens utilized demonstrate a lack of clear SOC for heavily pretreated, triple-class exposed patients with RRMM in real-world practice and result in poor outcomes. This supports a need for new treatments with novel mechanisms of action

Thromboelastography

Tromboelastografie (TEG) is een visco-elastische, globale stollingstest op volbloed, die aan het bed van de patiënt kan worden uitgevoerd en snel resultaten genereert. TEG visualiseert hierbij de effecten van zowel plasmafactoren als cellulaire bloedelementen. Aanvankelijk werd TEG voornamelijk in de lever-, cardio- en traumachirurgie gebruikt bij de analyse en correctie van complexe stollingsstoornissen. Tegenwoordig vindt de techniek zijn toepassing in zeer diverse, zowel klinische als experimentele, gebieden betreffende hemostase en trombose. Het primaire doel van het proefschrift is om de kennis van TEG bij clinici en onderzoekers werkzaam op het terrein van de hemostase en trombose te verbeteren, waarbij zowel de mogelijkheden als de beperkingen van de techniek worden belicht. De rol die “point-of-care” testen van hemostase (o.a. TEG) spelen bij het voorspellen en behandelen van massaal bloedverlies wordt geëvalueerd. Daarnaast zijn TEG referentiewaarden bepaald, waarbij duidelijke effecten van leeftijd, geslacht en orale anticonceptiva op de stolling zijn aangetoond. Ook is de TEG techniek gevalideerd wat betreft de analyse en detectie van een tekort aan bloedplaatjes. TEG bleek goed in staat om de effecten van (getransfundeerde) bloedplaatjes en rode bloedcellen op de stolling aan te tonen. De techniek kan wellicht nuttig zijn als in vivo kwaliteitstest van bloedproducten. Tenslotte lijkt TEG bruikbaar bij patiënten met sikkelcelziekte ter detectie van zowel verhoogde stollingsstatus alsook de gunstige effecten van behandeling met hydroxyureum hierop. Thromboelastography (TEG), a global test of haemostasis, has the advantage over classical coagulation tests that it is performed bedside and in whole blood, offering a rapid overview of the sum of the cumulative effects of plasma factors as well as interacting cellular elements. TEG was initially used to guide transfusion in the setting of hepatic, cardiovascular and trauma surgery, but nowadays its use has been expanded to all other areas of haemostasis and thrombosis testing. The scope of this thesis is to improve the understanding of TEG technology for clinicians working in the field of haemostasis, making them aware of the possibilities, but also of the limitations of TEG in coagulation monitoring. For this purpose, an overview is given on the role of TEG and other point-of-care tests of haemostasis in both the prediction and treatment of massive blood loss. Further, TEG is validated by obtaining and describing own normal reference ranges. In contrast to classical coagulation tests, and in spite of its global character, TEG is able to detect the effects of age, gender and oral anticonceptives on the coagulation profile. Also, TEG seems capable in demonstrating the effects of platelets and red blood cells on haemostasis and has potential as an in vivo quality test of blood products. Finally, TEG might play a future role in patients with sickle cell disease as the technique is able to monitor the pro-coagulant status of these patients as well as the effects of treatment with hydroxyurea on this status.

Thrombocytopenia affects plasmatic coagulation as measured by thrombelastography

Thrombelastography (TEG) is used as a point-of-care test of hemostasis. Different components of the test tracing are considered to reflect various parts of the hemostatic system and to distinguish low platelet count, platelet dysfunction or both from lack of plasmatic coagulation factors. To analyze the influence of one single element of the coagulation system, namely the platelet count, we used TEG serially in patients with well documented transient thrombocytopenia. A total of 189 TEG analyses were performed from 16 patients with a hematological malignancy in remission, receiving consolidation courses of chemotherapy. TEG outcomes using unmanipulated and citrated blood samples at a median of 11 times (range 1 - 17) in the same patients during the decrease of platelet count in response to chemotherapy were compared with outcomes in 120 healthy adults from various age categories. We found a correlation (r = 0.7, P <0.001) between TEG clot strength (maximum amplitude) and platelet count. Moreover, platelet count was correlated respectively with the initial rate of clot formation (reaction time and clotting time), the rate of clot growth (alpha angle), and also with maximum thrombus generation, time to maximum thrombus generation and total thrombus generation. We conclude that platelet count not only affects the strength of clot formation, as was expected, but also all other phases of plasmatic coagulation. Citration of the blood sample, aiming at easy storage of the material, masked some of the important biological parameters of coagulation. Blood Coagul Fibrinolysis 21:389-397 (C) 2010 Wolters Kluwer Health vertical bar Lippincott Williams & Wilkins