Israel Medical Association Journal

Background: Primary central nervous system lymphoma (PCNSL) is a rare aggressive non-Hodgkin's lymphoma. There are limited data on the management of PCNSL outside of clinical trials.

Objectives: To report experience with three main high-dose methotrexate (HDMTX)-based protocols for PCNSL treatment at one medical center.

Methods: We conducted a retrospective review of the medical records of patients diagnosed with PCNSL who were treated at Soroka Medical Center between 2007 and 2019.

Results: The study included 36 patients, median age 64.9 years; 33 patients received a HDMTX backbone induction therapy, 21 (58.3%) received consolidation treatment in addition. In the entire cohort, 25 patients (75.7%) achieved complete remission (CR, CRu-unconfirmed), with mean progression-free survival (PFS) 32 ± 6.9 months and median overall survival (OS) 59.6 ± 12.4 months. More aggressive regiment such as combination of rituximab, HDMTX, cytarabine and thiotepa had better responses 5 (100%) CR, but also a higher incidence of side effects such as neutropenic fever 5 (100%). In subgroup analysis by age (younger vs. older than 60 years), the PFS was 24.2 vs. 9.3 months, and OS was 64.1 vs. 19.4 months, respectively.

Conclusions: A difference in CR and PFS favored a more aggressive protocol, but the toxicity of the multiagent combinations was significantly higher. The prognosis in younger was better than in older patients, with higher rates of CR, PFS, and OS, although not statistically significant. Overall treatment outcomes are encouraging; however, there is a real need for an adaptive approach for older patients and balancing among the effectiveness and side effects.

Advances in Lymphoma management have resulted in significant improvements in patient outcomes over the last 50 years. Despite these developments, cardiotoxicity from lymphoma treatments remains an important cause of mortality and morbidity in this cohort of patients. We outlined the most common cardiotoxicities associated with lymphoma treatments and their respective investigation and management strategies, including the role of cardiac pre-assessment and late effects monitoring.

Several novel strategies have emerged in the last decade as potential therapies for patients with chemorefractory lymphoproliferative diseases and acute leukemia. While these treatments include exciting drugs that dramatically change the landscape of treatment, the organ-toxicity profile associated with these therapies may be significant. This article focuses on cardiac disorders associated with chimeric antigen receptor T-cell (CAR-T) therapy, as well as with novel regimens for acute leukemia

Background: Immune thrombocytopenia (ITP) is an autoimmune disorder of variable origin that results in bleeding and decreased platelet count. Autoimmune abnormalities have been described in patients with malignancies including non-Hodgkin's lymphoma but are rarely described in patients with Hodgkin's lymphoma.

Objectives: To describe an unusual presentation of Hodgkin's lymphoma in an unusual age and alarm pediatricians of the challenging diagnosis.  

Methods: We present two cases that highlight an unusual clinical presentation of childhood Hodgkin's lymphoma occurring at an atypical age.

Results: Over a 4-year period, two children aged 5 and 6 years were admitted for suspected ITP, both had cervical lymphadenopathy. Bone marrow examination showed no evidence of tumor or fibrosis. Biopsy of the lymph node was possible only after administration of intravenous immunoglobulins and normalization of the platelet count. Platelet counts increased after initiation of chemotherapy.

Conclusions: The identification of the clinical presentation of ITP as a possible presentation of Hodgkin's lymphoma is important to facilitate timely diagnosis and management.

Background: Whole-body integrated positron emission tomography / contrast-enhanced computed tomography (PET/CT) scan is increasingly used in cutaneous lymphomas. However, the value of PET/CT in the detection of cutaneous lesions in primary cutaneous B-cell lymphoma (PCBCL) has barely been investigated.

Objectives: To investigate the diagnostic accuracy of PET/CT in tracking cutaneous involvement in PCBCL.

Methods: A retrospective study was conducted on 35 consecutive patients diagnosed with cutaneous B-cell lymphoma according to the World Health Organization classification who were evaluated with PET/CT as the initial staging procedure before treatment.

Results: Thirty-five patients met the study criteria. In two patients extracutaneous disease was detected by PET/CT and CT and confirmed by biopsy. Of the 33 patients with PCBCL, 26 (79%) had small cell PCBCL (18 marginal-zone, 8 follicle-center lymphoma) and 7 (21%) had large cell PCBCL (3 follicle-center, 3 leg-type, 1 indeterminate). PET/CT detected skin lesions in 3 of 26 patients (12%) with small-cell PCBCL as compared to 6 of 7 patients with large-cell PCBLC (86%), a 7.4-fold detection risk (95% confidence interval, 2.4–22, P = 0.004). The PET-positive subgroup was characterized by larger lesion size (P < 0.001) and a higher Ki-67 proliferation index (P < 0.001).

Conclusions: The sensitivity of PET/CT for detecting cutaneous involvement of lymphomas is low for small-cell PCBCL but high for large-cell types, and thus may facilitate therapeutic strategies.

Background: Breast implant-associated anaplastic large cell lymphoma (ALCL) is a rare type of non-Hodgkin's lymphoma that is found around breast implants. ALCL was discovered only two decades ago. In Israel we currently have four diagnosed cases (as of 2018). Until recently, the estimated incidence was 1:300,000 women with breast implants, while recent reports range from 1:3817 to 1:30,000. 

Objectives: To determine the occurrence of breast implant-ALCL in Israel.

Methods: We conducted a retrospective analysis of the four patients diagnosed with ALCL in Israel. Cytology was confirmed and the clinical data was collected. Based on the estimated number of women with breast implants in Israel, a calculation of the true incidence was completed.

Results: The incidence in Israel is significantly higher than the older incidence reports indicate. We estimated that the lifetime prevalence of the disease is 4:60,000 women with a textured breast implant, or 1:15,000 women with a textured breast implant in Israel.

Conclusions: ALCL is not common. We support the claim that the prevalence is significantly higher than what was initially described. This finding has clinical and medicolegal implications that should be addressed accordingly.

Background: Enlarged lymph nodes (ELN) pose a great diagnostic challenge. They may represent the first clinical finding of a hematologic disease or other malignancy and may be an indication of a wide range of infectious and non-infectious diseases. Because many patients undergo percutaneous biopsy, surgical excisional biopsy is not often considered.

Objectives: To analyze indications for a patient's referral for surgical biopsy of ELN and diagnostic steps to follow until referral, and to determine the number of ELN.

Methods: A retrospective study was conducted of prospectively collected data of patients who underwent surgical biopsy of ELN from January 2004 to December 2013.

Results: Of 118 patients who underwent surgical biopsy of ELN, only 52 (44%) had needle biopsy (NB) before referral. Lymphoma was diagnosed by NB in 24 (46%) of the referred patients. In patients with a previous diagnosis of lymphoma, NB of ELN yielded a sensitivity of 67% and specificity of 79%. In patients with lymphadenopathy but with no previous history of malignancy, sensitivity for lymphoma was 68% and specificity was 71%. The investigative time period until final diagnosis was 3 months in patients who had NB but only 1.25 months in patients who were referred directly for surgery (P < 0.0001).

Conclusions: Surgical biopsy of ELN still has a place in the clinical evaluation of patients with ELN. Surgery may significantly reduce the length of investigation and prevent unnecessary diagnostics, especially in patients with suspected lymphoma recurrence.

Background: Diffuse large B-cell lymphoma (DLBCL) accounts for 30% of all non-Hodgkin lymphomas (NHL) and 80% of agressive lymphomas. Besides the traditional International Prognostic Index (IPI), some other factors may also influence the prognosis of DLBCL patients.

Objectives: To study how the genetic polymorphisms in the metabolic pathway influence the event-free and overall survivals and therapeutic responses in DLBCL.

Methods: The study was comprised of 51 patients (32 men, 19 women). The average age was 53.1 years. DLBCL was diagnosed between 2011 and 2016 and the average follow-up time was 3.78 years. These patients received 1–8 cycles (an average of 6.2 cycles) of rituximab, cyclophosphamide, doxorubicin, vincristin, prednisolon (R-CHOP) immunochemotherapy. Real-time polymerase chain reaction was used to determine the genetic polymorphisms of CYP2E1, GSTP1, NAT1, and NAT2 genes.

Results: Our results showed that the polymorphisms of CYP2E1, GSTP1, and NAT1 genes did not influence the prognosis of DLBCL patients significantly. In terms of the NAT2 gene, GG homozygous patients showed slightly better therapeutic response and survival results compared to those bearing an A allele; however, the differences were not statistically significant.

Conclusions: Our results could not confirm that genetic polymorphism in metabolic pathways has any predictive role in DLBCL.