Primary Central Nervous System Lymphoma

Although non-Hodgkin’s lymphoma (NHL) is a frequent cancer worldwide, primary central nervous system (CNS) lymphoma (PCNSL) is a rare presentation, with an incidence of less than 0.5 per 100,000 persons-years in the western world. In the vast majority of cases, it has the histology of a diffuse large B-cell lymphoma (DLBCL) and is a hardly curable disease with high relapse risk. Therapeutic options are limited by blood-brain barrier penetration of drugs and because of its low-incidence high-grade evidence from large studies is lacking, current management being based on reports on rather small cohorts. The current standard first-line treatment for PCNSL consists of high-dose methotrexate (HD-MTX) in combination with a variety of drugs and consolidation whole-brain radiotherapy, the latter being progressively replaced by chemotherapy. For patients relapsing after first-line treatment, intensive chemotherapy with autologous stem cell support is a feasible and relatively safe salvage therapy. In the present chapter, we briefly discuss primary central nervous system lymphoma management and review current therapeutic options and evidence-based recommendations. We discuss the role of whole-brain radiotherapy (WBRT) and new prospects to avoid this side effect-ridden approach. Also, we will look at new therapeutic approaches currently under investigation, including immunotherapy

Unexpected hope for a multiple myeloma patient

Multiple myeloma (MM) is a plasma cell neoplasm, characterized by periods of remission and relapses. The emergence of novel therapies, with multiple mechanisms of action and fewer adverse reactions, brings more and better options and also a higher survival rate. However, MM is still an incurable disease, and patients eventually become refractory to an extensive range of therapies. We present the case of a patient diagnosed with MM standard risk, who was at first refractory to multiple treatment regimens, and then had an unexpected and stable complete response to a newer drug of the same class

LEUKEMIJA I TRUDNOĆA. NIJE DALJE ŠTETNA POVEZANOST?

Purpose. Even though there are no solid data regarding chemotherapy treated leukemia during pregnancy, the results based on short series reports show that the management of such condition can be safely achieved during the second and third trimester. We present three personal cases of pregnant women treated with cytostatic agents, two of them accidentally receiving complete chemotherapy during the entire pregnancy without malformative consequences. First case. A 19 yrs old woman diagnosed with chronic myeloid leukemia who conceived spontaneously and mistook the pregnancy signs for a relapse of the disease. During the pregnancy she continued the treatment, receiving until the fifth month an association of Hydroxyurea and alfa-interferon and afterwards switched to Imatinib until term. She presented at 38–39 weeks and delivered by cesarean section a little girl of 3510 g in a perfect state of health. The blood count of both mother and child were normal. Second case. A similar situation in a young woman with lymphoblastic acute leukemia under treatment with Vincristin, Methotrexat, Purinethol. She presented in advanced spontaneous labour at 33–34 weeks and delivered a little girl of 1700 g without malformative signs and normal blood count. Third case. A 17 years old girl who was diagnosed with acute myeloid leukemia at 29 weeks pregnancy. She received induction chemotherapy with Ara-C, due to the significant bone marrow infiltrate and disease induced disseminated intravascular coagulopathy. She presented premature uterine contractions at 32 weeks and delivered by cesarean section a premature boy of 1750g with Apgar score 8. The infant did not present any malformation (by clinical and ultrasound examination) and the blood count was normal. The studies have shown so far that in the case of chronic myeloid leukemia, the treatment with Imatinib was associated with 50% apparently normal live infants and that chemotherapy for acute leukemia during the second or third trimester may not require termination of pregnancy, because both remission and delivery of a normal infant are likely to be obtained.SAŽETAK. Cilj. Uopće nema čvrstih podataka o kemoterapijom liječenim leukemijama tijekom trudnoće. Rezultati na temelju kratkih izvješća pokazuju da liječenje tijekom drugog i trećeg tromjesečja može biti uspješno obavljeno. Prikazujemo tri trudnice liječene citostaticima, dvije od njih su bez posljedičnih malformacija primale kompletnu kemoterapiju tijekom cijele trudnoće. Prvi slučaj. Žena od 19 godina koja je spontano zanijela i krivo shvatila znakove trudnoće kao recidiv bolesti. Tijekom trudnoće je nastavila liječenjem, primivši do petog mjeseca smjesu hidroksiureje i -interferona i zatim do termina imatinib. Javila se s 38–39 tjedana trudnoće te je carskim rezom rodila savršeno zdravu malu djevojčicu težine 3510 grama. Krvna slika majke i djeteta je bila potpuno normalna. Drugi slučaj. Sličan slučaj mlade žene s limfoblastičnom akutnom leukemijom, liječenom vinkristinom, metotreksatom, purinetolom. Javila se u uznapredovalom porodu s 33–34 tjedana te je rodila djevojčicu tešku 1700 grama, bez malformacija i s normalnom krvnom slikom. Treći slučaj. Djevojka od 17 godina kojoj je s 29 tjedana trudnoće dijagnosticirana akutna mijeloična leukemija. Primila je indukcijsku kemoterapiju Ara-C-om, zbog značajne infiltracije koštane srži te bolešću uzrokovane diseminirane intravaskularne koagulopatije. S 32 tjedna počeli su trudovi te je carskim rezom rodila nedonošena dječačića težine 1750 grama s Apgar zbrojem 8. Dijete nije imalo malformacija ni klinički niti ultrazvučnim pregledom. Krvna slika je bila normalna. Do sada su studije pokazale da kronična mijeloična leukemija, liječena imatinibom, u 50% slučajeva rezultira rađanjem zdrava djeteta te da kemoterapija akutne leukemije tijekom drugog i trećeg tromjesečja trudnoće na zahtijeva prekid trudnoće, jer se može postići remisija bolesti i rađanje normalna djeteta

LEUKEMIJA I TRUDNOĆA. NIJE DALJE ŠTETNA POVEZANOST?

Purpose. Even though there are no solid data regarding chemotherapy treated leukemia during pregnancy, the results based on short series reports show that the management of such condition can be safely achieved during the second and third trimester. We present three personal cases of pregnant women treated with cytostatic agents, two of them accidentally receiving complete chemotherapy during the entire pregnancy without malformative consequences. First case. A 19 yrs old woman diagnosed with chronic myeloid leukemia who conceived spontaneously and mistook the pregnancy signs for a relapse of the disease. During the pregnancy she continued the treatment, receiving until the fifth month an association of Hydroxyurea and alfa-interferon and afterwards switched to Imatinib until term. She presented at 38–39 weeks and delivered by cesarean section a little girl of 3510 g in a perfect state of health. The blood count of both mother and child were normal. Second case. A similar situation in a young woman with lymphoblastic acute leukemia under treatment with Vincristin, Methotrexat, Purinethol. She presented in advanced spontaneous labour at 33–34 weeks and delivered a little girl of 1700 g without malformative signs and normal blood count. Third case. A 17 years old girl who was diagnosed with acute myeloid leukemia at 29 weeks pregnancy. She received induction chemotherapy with Ara-C, due to the significant bone marrow infiltrate and disease induced disseminated intravascular coagulopathy. She presented premature uterine contractions at 32 weeks and delivered by cesarean section a premature boy of 1750g with Apgar score 8. The infant did not present any malformation (by clinical and ultrasound examination) and the blood count was normal. The studies have shown so far that in the case of chronic myeloid leukemia, the treatment with Imatinib was associated with 50% apparently normal live infants and that chemotherapy for acute leukemia during the second or third trimester may not require termination of pregnancy, because both remission and delivery of a normal infant are likely to be obtained.SAŽETAK. Cilj. Uopće nema čvrstih podataka o kemoterapijom liječenim leukemijama tijekom trudnoće. Rezultati na temelju kratkih izvješća pokazuju da liječenje tijekom drugog i trećeg tromjesečja može biti uspješno obavljeno. Prikazujemo tri trudnice liječene citostaticima, dvije od njih su bez posljedičnih malformacija primale kompletnu kemoterapiju tijekom cijele trudnoće. Prvi slučaj. Žena od 19 godina koja je spontano zanijela i krivo shvatila znakove trudnoće kao recidiv bolesti. Tijekom trudnoće je nastavila liječenjem, primivši do petog mjeseca smjesu hidroksiureje i -interferona i zatim do termina imatinib. Javila se s 38–39 tjedana trudnoće te je carskim rezom rodila savršeno zdravu malu djevojčicu težine 3510 grama. Krvna slika majke i djeteta je bila potpuno normalna. Drugi slučaj. Sličan slučaj mlade žene s limfoblastičnom akutnom leukemijom, liječenom vinkristinom, metotreksatom, purinetolom. Javila se u uznapredovalom porodu s 33–34 tjedana te je rodila djevojčicu tešku 1700 grama, bez malformacija i s normalnom krvnom slikom. Treći slučaj. Djevojka od 17 godina kojoj je s 29 tjedana trudnoće dijagnosticirana akutna mijeloična leukemija. Primila je indukcijsku kemoterapiju Ara-C-om, zbog značajne infiltracije koštane srži te bolešću uzrokovane diseminirane intravaskularne koagulopatije. S 32 tjedna počeli su trudovi te je carskim rezom rodila nedonošena dječačića težine 1750 grama s Apgar zbrojem 8. Dijete nije imalo malformacija ni klinički niti ultrazvučnim pregledom. Krvna slika je bila normalna. Do sada su studije pokazale da kronična mijeloična leukemija, liječena imatinibom, u 50% slučajeva rezultira rađanjem zdrava djeteta te da kemoterapija akutne leukemije tijekom drugog i trećeg tromjesečja trudnoće na zahtijeva prekid trudnoće, jer se može postići remisija bolesti i rađanje normalna djeteta

Mast Cell Diseases in Practice and Research:Issues and Perspectives Raised by Patients and Their Recommendations to the Scientific Community and Beyond

Background: Since 2010, patients and physicians have collaborated to understand unmet needs of patients with mast cell diseases, incorporating mastocytosis and mast cell activation disorders, which include mast cell activation syndromes. Objective: This Open Innovation in Science project aims to expand understanding of the needs of patients affected by mast cell diseases, and encourage global communication among patient advocacy groups, physicians, researchers, industry, and government. A major aim is to support the scientific community's efforts to improve diagnosis, management, therapy, and patients’ quality of life by addressing unmet needs. Methods: In collaboration with mast cell disease specialists, 13 patient advocacy groups from 12 countries and regions developed lists of top patient needs. A core team of leaders from patient advocacy groups collected and analyzed the data and proposed possible actions to address patient needs. Results: Findings identified similarities and differences among participating countries in unmet needs between patients with mastocytosis and those with mast cell activation syndromes. Issues emphasized struggles relating to the nature and rarity of mast cell diseases, their impact on quality of life, the diagnostic process, access to appropriate care, more effective treatment, and the need for research. Conclusions: Solutions vary across countries because situations differ, in particular regarding the existence of and access to centers of excellence and reference centers. Multifaceted mast cell activation syndrome barriers necessitate innovative approaches to improve access to appropriate care. The outcomes of this project should greatly support scientists and clinicians in their efforts to improve diagnosis, management, and treatment of patients with mastocytosis and mast cell activation disorders

Nine year follow-up of a rare case of angioedema due to acquired C1-inhibitor deficiency with late onset and good response to attenuated androgen

Abstract Background Angioedema due to acquired deficiency of C1-inhibitor (C1-INH-AAE) is a rare disease sharing some clinical and laboratory similarities with hereditary angioedema, but with late onset and no positive family history. The underlining cause may be malignant or due to autoimmune diseases, but some cases remain idiopathic. Case presentation We report a case of a 75 year old woman suffering from recurrent episodes of angioedema since the age of 66, considered first induced by treatment with angiotensin-converting-enzyme inhibitors (ACEI). She continued to have angioedema attacks during 6 years after discontinuation of ACEI, until evaluation in our clinic in 2014, when C1 inhibitor esterase (C1-INH) deficiency was confirmed. The extended medical evaluation for inflammatory, allergic, autoimmune and neoplasic diseases was negative. C1-INH and complement fraction C4 plasma levels were significantly decreased at all measurements, but no diagnostic criteria for diseases known to induce C1-INH deficiency could be found. We first initiated daily prophylactic treatment with tranexamic acid, with no amelioration after 3 months. During the last and most severe attack, with the first facial and laryngeal edema, we have switched to attenuated androgen danazol. The evolution was very good, with prompt remission of angioedema and significant increase of C1-INH and C4 plasma levels after 2 weeks of daily danazol use. She completed 3 years of continuous treatment with low daily maintenance dose of danazol (ongoing), with no angioedema attack. We closely monitored C1-INH and C4 plasma levels, possible danazol side effects and any signs suggesting late onset of C1-INH deficiency causal disease. Conclusion We reported a particular case of rare angioedema due to acquired deficiency of C1-inhibitor, which has no clear cause after long follow-up, but good response to attenuated androgen. We concluded that the awareness of angioedema due to C1-INH deficiency should be increased within medical community and therapeutic options should be more clearly indicated and available for all diagnosed cases

REGULATORY T CELLS AND THE MICROENVIRONMENT OF THE MALIGNANT B CELL OF CHRONIC LYMPHOCYTIC LEUKEMIA

In recent years understanding and modulating the tumor microenvironment (MT) has been the focus of a scientifically and clinically intense study. The role of T regulatory cells (Tregs) were investigated in terms of the suppression of tumor-specific immune responses and the establishment of an immunosuppressive tumor microenvironment (1). Regulatory T cells have a fundamental function in maintaining immune homeostasis in healthy individuals, and in cancer and in particular in haematological malignancies they seem to play a rather controversial role. Furthermore an increased frequency of Treg cells has been associated with tumor progression and has been correlated with an increased risk of death and reduced survival (2). The role of T cells in the pathogenesis of chronic lymphocytic leukemia has recently gained special attention due to the constant interaction between neoplastic B cells with the micromedium substrate and T cells. There is often a relatively large number of regulatory T cells in lymphoid tissues of CLL patients, that could affect the normal immune function (3)

Chapter 8 : Primary central nervous system lymphoma.

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Idiopathic thrombocytopenic purpura (ITP) – new era for an old disease

Immune thrombocytopenia is an autoimmune hematological disorder characterized by severely decreased platelet count of peripheral cause: platelet destruction via antiplatelet antibodies which may also affect marrow megakaryocytes. Patients may present in critical situations, with cutaneous and/or mucous bleeding and possibly life-threatening organ hemorrhages (cerebral, digestive, etc.) Therefore, rapid diagnosis and therapeutic intervention are mandatory