Breast Implant-Associated Anaplastic Large Cell Lymphoma: Where Hematology and Plastic Surgery Meet.

Breast implant insertion for breast reconstruction or breast augmentation is a developing procedure, with high demand worldwide-being the second most common plastic surgery in the US as of 2022. Breast-implant-associated anaplastic large cell lymphoma (BIA-ALCL) is T-cell, non-Hodgkin lymphoma, typically CD30+, ALK-, presenting with fluid collection in the inner aspect of the peri-implant capsule in most patients, with the onset exceeding 1-year after implantation. The mean time between breast implant insertion and BIA-ALCL development is 7-10 years. The main risk factor is the use of textured implants because of their susceptibility to triggering local inflammation and immune stimulation finally leading to lymphoproliferation. Genetic predispositions to hereditary breast cancer increase the risk of disease development as well. BIA-ALCL seems to be underestimated in many countries and the initial symptom-seroma might be overlooked and misdiagnosed. Despite its rarity, the awareness of the disease should be improved among patients and medical professionals. This paper summarizes epidemiology, etiopathogenesis, differential diagnosis, and treatment-both surgical and hematological approaches.

Rapid progression of myelofibrosis in polycythemia vera patient carrying SRSF2 c.284C>A p.(Pro95His) and unique ASXL1 splice site c.1720-2A>G variant.

BACKGROUND: The prognosis in polycythemia vera (PV) is comparatively favorable, but individual myelofibrosis/leukemic progression risk is heterogeneous. About a quarter of patients progress to the fibrotic phase after 20 years. METHODS: Multiplex PCR, allele-specific qPCR, high-resolution melt analysis, and Sanger sequencing were used to detect BCR-ABL, JAK2, ASXL1, SRSF2, U2AF1, and IDH1/2 variants. RESULTS: Herein, we present a PV patient with rapid progression to secondary myelofibrosis probably due to the coexistence of homozygous JAK2 V617F mutation, SRSF2 c.284C>A p.(Pro95His) and splice site variant of ASXL1 c.1720-2A>G. The detected ASXL1 variant was first described in Bohring-Opitz syndrome and has not been reported in hematological malignancies so far. In the presented case, the ASXL1 VAF was stable (50%) during the 4-year follow-up, despite an evident increase in the JAK2 V617F VAF. Family history revealed cerebral palsy in the patient's grandson; however, germline character of the ASXL1 variant was excluded. CONCLUSION: The biological consequences of the variant acquisition by hematopoietic stem cells (HSC) seem to be similar to other mutations of ASXL1 responsible for the truncation of ASXL1 protein, formation of hyperactive ASXL1-BAP1 (BRCA1-associated protein-1) complexes, and finally, the promotion of aberrant myeloid differentiation of HSC. Our report supports the hypothesis that ASXL1 alteration cooperates with JAK2 V617F leading to biased lineage skewing, favoring erythroid and megakaryocytic differentiation, accelerating the progression of PV to the fibrotic phase.

The Outcomes of Ponatinib Therapy in Patients With Chronic Myeloid Leukemia Resistant or Intolerant to Previous Tyrosine Kinase Inhibitors, Treated in Poland Within the Donation Program.

INTRODUCTION: Tyrosine kinase inhibitors (TKIs) have greatly improved the treatment outcome for most patients with chronic myeloid leukemia (CML). Ponatinib is a new pan-inhibitor of TK active in resistant CML. This study aimed to evaluate the efficacy and safety of ponatinib in patients suffering from CML. PATIENTS AND METHODS: This multicenter, non-randomized, observational, retrospective study evaluated the efficacy and safety of ponatinib administered in adult CML patients in any disease phase, including those with a detected ABL T315I mutation, which were resistant or intolerant to previous-generation TKIs. The study comprised 43 patients benefiting from the ponatinib donation program who were treated in 16 Polish centers. RESULTS: For patients who started treatment with ponatinib in chronic phase (CP) (n = 23) and in accelerated phase (AP) (n = 3) the median time on ponatinib was 19.5 months (range: 1.0-35.4), and 31.7 months (range: 31.0-34.1), respectively. All these patients were in CP after 1 month of treatment and at the end of observation - none of them progressed to AP or blastic phase (BP) during the study, meaning that progression-free survival was 100% at the end of observation (35.4 months). The estimated 2-year survival in this group of patients was 84%. For all 43 patients, median survival was not reached (lower quartile 6.3 months), and estimated 2-year survival was 60%. CONCLUSION: Our analysis confirmed ponatinib efficacy in a significant proportion of patients heavily pre-treated with TKIs achieving durable responses in both CP and AP/BP CML groups.

Hodgkin lymphoma of the elderly patients: a retrospective multicenter analysis from the Polish Lymphoma Research Group.

We retrospectively analyzed long-term disease outcome of 350 elderly Hodgkin Lymphoma (eHL) patients treated with ABVD/ABVD-like regimen enrolled in the PLRG-R9 study between 2001 and 2013 in Poland. Complete remission was reported for 73% of early (ES) and 61% advanced stage (AS) patients. Nine (10%) ES and 56 (20%) AS patients have died. With the median follow-up of 36 (1-190) months, 3-year EFS and OS was 0.74 (95%CI: 0.63-0.85) and 0.90 (95%CI: 0.82-0.98) for ES; 0.51 (95%CI: 0.44-0.57), and 0.81 (95%CI: 0.75-0.86) for AS patients, respectively. For ES patients, Cox regression revealed ECOG <2 and age >70 as predictive for inferior OS and EFS. For AS patients, the most predictive for OS was the presence of cardiovascular disorders (CVD) (p = .00044), while for EFS four factors were significantly associated with a poor outcome: ECOG< 2, age >70 years, CVD and extranodal disease. In conclusion, CVD significantly impacts outcomes of ABVD-treated advanced eHL patients.

Successful treatment of pulmonary candidiasis and aspergillosis in patient with refractory Hodgkin lymphoma using micafungin - case study and brief literature review.

The number of patients with hematological malignancies who develop invasive fungal disease (IFD) has increased dramatically in recent decades. This increase is attributed to impairment of the host immune system due to intensive cytotoxic chemotherapies, use of corticosteroids and profound immunosuppression after hematopoietic stem cell transplantation (HSCT). Additionally, the increasing prevalence of fungal infections caused by emerging and rare pathogens, IFD of mixed etiology or of atypical localization is observed. There are also much more patients with IFD who do not belong to a well-described risk group, like patient with lymphoproliferative disorders. Within this heterogeneous group of patients, IFD epidemiology is not well defined and antifungal prophylaxis practices vary. The aim of this paper is to present the case of a 58-year-old patient with refractory Hodgkin disease, focusing on infectious complication after subsequent lines of chemotherapy. During deep and prolonged neutropaenia the patient developed symptoms of pneumonia. Despite antifungal prophylaxis with fluconazole, IFD of mixed etiology with the presence of Candida glabrata and Aspergillus fumigatus was diagnosed. The infection showed a poor response to monotherapy with liposomal amphotericin B, but was successfully treated with therapy involving micafungin. Analysis of the presented case demonstrated the necessity of new approaches to the prevention of IFD in patients with lymphoproliferative disorders heavily pretreated with numerous chemotherapy protocols. Prolonged neutropenia and high corticosteroid exposure put these patients in high risk of IFD like patients with acute myeloid leukemia/myelodysplastic syndrome or after allogeneic HSCT.

Mean platelet volume as a predictive marker for venous thromboembolism and mortality in patients treated for diffuse large B-cell lymphoma.

It has been suggested that mean platelet volume (MPV) is associated with the risk of venous thromboembolism (VTE) and increased mortality in patients with cancer. We evaluated the association of MPV with VTE and mortality in patients treated for diffuse large B-cell lymphoma (DLBCL). Retrospective analyses were performed on 184 adult patients (median age 59, 55% men), of whom 141 were newly diagnosed, and 43 had relapse/refractory DLBCL. During the observation period (median 499 days), 39 (21.2%) patients developed VTE. Thirty-nine patients died of various causes. In univariate analysis, only the MPV and the treatment line were associated with the occurrence of VTE. In multivariate analysis, MPV ≤10th percentile (odd ratio 1.81; 95% confidence interval 1.06-3.11, p = 0.03) and salvage therapy (odd ratio 2.46; 95% confidence interval 1.66-3.65, p < 0.001) remained significant factors for developing VTE. Other patient-related factors-age, gender, disease-related factors-stage, the International Prognostic Index score, DLBCL subclassification (the germinal centre type and the activated B-cell type), Ki-67 index and VTE risk assessment model failed to be prognostic for VTE. In a Kaplan-Meier analysis, patients with MPV >10th percentile had statistically significantly longer VTE-free survival than patients with lower MPV. In multivariable Cox regression analysis, MPV ≤10th percentile (hazard ratio 5.56, p < 0.001), male gender, age, Ki-67 index, high or high-intermediate International Prognostic Index and VTE development (hazard ratio 7.81, p = 0.029) all significantly correlated with the risk of mortality. The probability of survival was higher in patients with MPV >10th percentile. In conclusion, our results suggest that the pre-chemotherapy MPV value is a cheap and available parameter that may be a useful prognostic marker for a significant risk of VTE and inferior survival rates in patients with DLBCL.

Liposomal cytarabine in the prophylaxis and treatment of CNS lymphoma: toxicity analysis in a retrospective case series study conducted at Polish Lymphoma Research Group Centers.

Lymphomas with primary or secondary involvement of central nervous system (CNS) have poor prognosis despite specific treatment protocols which include whole brain radiotherapy and high-dose systemic and/or intrathecal chemotherapy. Toxicity of intrathecal liposomal cytarabine-based regimens collected between November 2006 and January 2012 was assessed retrospectively. Data from 120 adult lymphoma patients with, or at high risk of CNS involvement who received intrathecal liposomal cytarabine-based regimens at six Polish Lymphoma Research Group centres between November 2006 and January 2012 were assessed retrospectively. Patients were divided into three cohorts: A (high risk of CNS disease, n = 88), B (cerebrospinal fluid pleocytosis without neurological symptoms or pathological imaging findings, n = 7), and C (CNS disease/neurological involvement; n = 25). In all examined groups, toxicity of treatment was found to be acceptable (including the prophylactic setting). None of the patients in cohorts A or B who took intrathecal liposomal cytarabine 50 mg, repeated every 2-4 weeks (mean 3.8 doses) had experienced a CNS relapse at a median follow-up time of 3 years. Patients in cohort C had a 76 % overall neurological response rate (including a 40 % complete response rate) and median overall survival of 4.8 years. Regimens incorporating liposomal cytarabine seem to be safe and effective treatments for lymphomas with CNS involvement.

The JAK2 V617F mutational status and allele burden may be related with the risk of venous thromboembolic events in patients with Philadelphia-negative myeloproliferative neoplasms.

INTRODUCTION: Patients with Philadelphia-negative myeloproliferative neoplasms (Ph(-) MPNs) are at increased risk of thromboembolic and hemorrhagic complications. The aim of the study was to determine the relationship between JAK2 V617F mutational status, JAK2 V617F allele burden and the risk of vascular complications occurrence. MATERIALS AND METHODS: Analysis was performed in a cohort of 186 patients diagnosed with polycythemia vera (53), essential thrombocythemia (114), primary myelofibrosis (11), and unclassified MPN (8). The risk of vascular complications development was analyzed in 126 JAK2 V617F-positive patients with respect to allele burden assessed with allele-specific 'real-time' quantitative polymerase chain reaction (AS RQ-PCR). RESULTS: Overall prevalence of any vascular complications was 44.6%. Arterial thrombosis occurred in 20.4%, venous thromboembolism (VTE) in 11.3%, bleeding episodes in 24.7% of patients. Individuals harboring JAK2 V617F mutation, regardless of MPN type, were at higher risk of VTE (OR=5.15, 95%CI: 1.16-22.90, P=0.024), mainly deep vein thrombosis (DVT). JAK2 allele burden higher than 20% identified patients with 7.4-fold increased risk of VTE (95%CI: 1.6-33.7, P=0.004), but not of arterial thrombosis, neither of bleeding complications, and remained the only significant VTE risk factor in multivariate logistic regression. High allele burdens (over 50%) were strikingly associated with proximal DVT cases, but not with distal DVT. CONCLUSIONS: The group of MPN patients with JAK2 V617F allele burden higher than 20% may benefit the most from vigilant monitoring and appropriate prophylaxis against vascular events. Inclusion of JAK2 V617F mutant allele burden in new risk stratifications seems to be justified and requires controlled prospective trials.

Bendamustine-based therapy as first-line treatment for non-Hodgkin lymphoma.

Recently, bendamustine has become an important agent in the treatment for patients with lymphoid malignancies. Although the drug has received approval for second-line therapy in indolent lymphoma, a growing body of evidence suggests its efficacy and safety in first-line use. The results of randomised and observational studies with bendamustine as front-line therapy in non-Hodgkin lymphoma (NHL) with emphasis on efficacy and toxicity are presented. Furthermore, completed and ongoing clinical trials evaluating upfront bendamustine effectiveness in combination with other agents are discussed. The review refers mainly to indolent lymphoma, mantle cell lymphoma and aggressive lymphoma, as the most commonly diagnosed NHL types. Finally, we elaborated on the safety profile of bendamustine and the perspectives of using the drug as a first-line therapy.

Hodgkin lymphoma transformation of chronic lymphocytic leukemia: cases report and discussion.

B-cell chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL) is the most common form of leukemia affecting adults in Europe and North America. Large B-cell lymphoma known as Richter's syndrome (RS) may develop approximately in 3-15 % patients. Furthermore, other hematological malignancies may also occur as RS variants, among them-Hodgkin lymphoma (HL). CLL/SLL transformation into HL is observed in about 0.5 % of patients, and till now, fewer than 100 cases have been reported in the medical literature. We present two cases of HL transformation of CLL/SLL and review the previously published literature.