Leukemic conversion involving RAS mutations of type 1 CALR-mutated primary myelofibrosis in a patient treated for HCV cirrhosis: a case report.

Somatic frameshift mutations in exon 9 of calreticulin (CALR) gene are recognized as disease drivers in primary myelofibrosis (PMF), one of the three classical Philadelphia-negative myeloproliferative neoplasms (MPNs). Type 1/type 1-like CALR mutations particularly confer a favorable prognostic and survival advantage in PMF patients. We report an unusual case of PMF incidentally diagnosed in a 68-year-old woman known with hepatitis C virus (HCV) cirrhosis who developed a progressive painful splenomegaly, without anomalies in blood cell counts. While harboring a type 1 CALR mutation, the patient underwent a leukemic transformation in less than 1 year from diagnosis, with a lethal outcome. Analysis of paired DNA samples from chronic and leukemic phases by a targeted next-generation sequencing (NGS) panel and single-nucleotide polymorphism (SNP) microarray revealed that the leukemic clone developed from the CALR-mutated clone through the acquisition of genetic events in the RAS signaling pathway: an increased variant allele frequency of the germline NRAS Y64D mutation present in the chronic phase (via an acquired uniparental disomy of chromosome 1) and gaining NRAS G12D in the blast phase. SNP microarray analysis showed five clinically significant copy number losses at regions 7q22.1, 8q11.1-q11.21, 10p12.1-p11.22, 11p14.1-p11.2, and Xp11.4, revealing a complex karyotype already in the chronic phase. We discuss how additional mutations, detected by NGS, as well as HCV infection and antiviral therapy, might have negatively impacted this type 1 CALR-mutated PMF. We suggest that larger studies are required to determine if more careful monitoring would be needed in MPN patients also carrying HCV and receiving anti-HCV treatment.

Hemophagocytic lymphohistiocytosis: a rare complication of autologous stem cell transplantation.

Hemophagocytic lymphohistiocytosis (HLH) is a very severe and rare syndrome of pathologic immune activation characterized by cytopenia and clinical signs and symptoms of extreme inflammation. HLH is usually fatal without treatment so that accurate and timely diagnosis is very important. The syndrome occurs as a familial disorder (familial HLH - FLH) or as an acquired condition (secondary - sHLH) in association with a variety of pathologic states: infections, rheumatologic, malignant or metabolic diseases. Malignancy associated HLH is primarily reported in T÷NK (natural killer)-cell malignancies but also in B-cell neoplasms and other types of cancer. HLH has also been reported in rare cases as a highly fatal and difficult to diagnose complication of stem cell transplantation (SCT). In this paper, we present the case of a young male patient who underwent autologous SCT as consolidation therapy for a T÷NK-cell lymphoma, complicated with graft failure due to HLH. The patient was successfully treated with corticosteroids, Etoposide, Cyclosporine and immunoglobulins. As a particularity, he developed a second B-cell neoplasia a few months after SCT.

Secondary Acute Lymphoblastic Leukemia after Hodgkin's Lymphoma or a Coincidental Association of Two Hematological Malignancies?

ABSTRACT: Secondary acute lymphoblastic leukaemia (sALL), defined as acute lymphoblastic leukaemia following another malignancy, irrespective of previous treatment, is a rare disease, and its biological characteristics have not been accurately described. We report the case of a 24-year old patient followed for Hodgkin's lymphoma at our clinic, who develops and is diagnosed, less than a year after obtaining complete remission, as having pro-B acute lymphoblastic leukaemia This case has been a real diagnostic and treatment challenge, as sALL following another haematological malignancy is quite rare. CONCLUSION: It is necessary to better identify the prognostic factors of haematological malignancies in order to prevent the appearance of sALL.

Immunotherapy with rituximab in follicular lymphomas.

BACKGROUND: Non-Hodgkin Lymphomas (NHL) represent a recent and fascinating domain of hemato-oncology, in which remarkable progress has been made. The conventional treatments of indolent lymphomas do not extend the survival rate, nor do they cure. Recent directions are centered on using several new drugs that are capable of overcoming the mechanisms that are resistant to recovery. The initiation of immunotherapy (Rituximab in 1997) seems to have changed the natural evolution of follicular lymphomas (FL). It is possible that resistance to healing in follicular lymphomas may be neutralized with Rituximab by suppressing STAT-1 positive macrophages that are present in the cellular microenvironment.Thereinafter, the re-evaluation of recent models of prognostic and therapeutic paradigmas that were used in FL became compulsory.The purpose of the paper is to compare the evolution of patients with follicular lymphoma and the period of response, according to the treatments. MATERIAL AND METHOD: The study group consisted of the 71 patients diagnosed with follicular lymphoma, out of a total of 767 malignant lymphatic proliferations with B cells, for a period of 7 years (2002-2008), at the Hematology Department, Hospital Coltea, Bucharest and Hematology Department, Universitary Hospital, BucharestResults and conclusions: Combining chemotherapy with Rituximab had better results compared to the same chemotherapy, administered alone, both in induction and in case of relapse. The overall response rate in our study group was 74.7%, out of which 42.3% complete remissions. The overall response rate was 84.61% in the Rituximab group, compared to 68.88% in patients without Rituximab.