Ofatumumab with iphosphamide, etoposide and cytarabine for patients with transplantation-ineligible relapsed and refractory diffuse large B-cell lymphoma.

The efficacy of salvage treatment of diffuse large B-cell lymphoma (DLBCL) patients who relapse or progress (rrDLBCL) after initial therapy is limited. Efficacy and safety of ofatumumab with iphosphamide, etoposide and cytarabine (O-IVAC) was evaluated in a single-arm study. Dosing was modified for elderly patients. Patients received up to six cycles of treatment. The primary end-point was the overall response rate (ORR). Patients were evaluated every two cycles and then six and 12 months after treatment. Other end-points included progression-free survival (PFS), event-free survival (EFS), overall survival (OS) and safety. Seventy-seven patients received salvage treatment with O-IVAC. The average age was 56.8 years; 39% had an Eastern Cooperative Oncology Group (ECOG) performance status of at least 3; 78% had disease of Ann Arbor stage 3 or 4; 58% received one or more prior salvage therapies. The ORR for O-IVAC was 54.5%. The median duration of study follow-up was 70 months. The median PFS and EFS were 16.3 months each. The median OS was 22.7 months. Age, ECOG performance status and the number of prior therapy lines were independent predictors of survival. Treatment-related mortality was 15.5%. O-IVAC showed a high response rate in a difficult-to-treat population and is an attractive treatment to bridge to potentially curative therapies.

Primary cutaneous indolent B-cell lymphomas - a retrospective multicenter analysis and a review of literature.

Introduction: Primary cutaneous indolent B-cell lymphomas (PCBCLs) are not well characterized due to their rarity and indolent character.Methods: We retrospectively reviewed the data from 52 patients with primary cutaneous follicular lymphoma (PCFL) (n = 26), marginal zone lymphoma (PCMZL) (n = 25) or undefined PCBCL (n = 1) treated in 10 hematology centers in 1999-2019.Results: Patients characteristics and diagnostic approach: In almost half of the patients, pruritus or pain were present at diagnosis. The lesions were predominantly located on the head and trunk. The disease was present in a form of solitary infiltration or disseminated lesions with a similar frequency.Treatment details and outcomes: Surgery, radiotherapy, rituximab alone or combined with chemotherapy were applied as first-line treatment in 33%, 25%, 21% and 21% of patients, with complete response (CR) achieved by 94%, 83%, 50% and 70% of patients, respectively (p = 0.28). The median duration of response (DoR) was 65 months (95%CI 35-155).Survival: After the median follow-up time of 46 months (range: 3-225), the estimated 5-year overall survival (OS) and progression-free survival (PFS) were 93% and 54%, respectively.Discussion: Clinical presentation was largely consistent with the literature data, however, we observed some differences, including higher predilection to affect upper extremities (25%) and more frequent multifocal appearance in PCFCL (64%) and unifocal in PCMZL (70%).A high proportion of patients with indolent PCBCL achieved CR after the first-line therapy (77%), regardless of treatment mode. We did not find any impact of clinical features on treatment outcomes.Conclusions: All treatment modalities resulted in a high overall response rate. Surgery and/or radiotherapy are the optimal therapeutic options for patients with localized disease. The decision to treat systemically should rather be limited to the generalized form of the disease. High response rate, long duration of remission and excellent long-term survival confirm the truly indolent character of PCFCL and PCMZL.

Long-term Efficacy of Ibrutinib in Relapsed or Refractory Chronic Lymphocytic Leukemia: Results of the Polish Adult Leukemia Study Group Observational Study.

BACKGROUND/AIM: To study the long-term clinical efficacy and tolerability of ibrutinib monotherapy in real-world relapsed and refractory chronic lymphocytic leukemia (RR-CLL) patients outside clinical trials. PATIENTS AND METHODS: Clinical data of 171 RR-CLL patients treated with ibrutinib were collected within the observational study of the Polish Adult Leukemia Study Group. RESULTS: Median patient age was 64 years. Patients were pretreated with 3 (1-10) median lines of therapy, while 42 (24.6%) had 17p deletion. The median observation time was 40 months (range=1-59 months), while median ibrutinib monotherapy reached 37.5 months (range=0.4-59.2 months). Response was noted in 132 (77.2%) patients. The estimated 5-year progression-free survival (PFS) and overall survival (OS) rates were 61.1% (95%CI=49.3-70.9%) and 56.8% (95%CI=45.6-66.6%), respectively. At the time of analysis 97 (56.7%) remained under ibrutinib monotherapy. CONCLUSION: Ibrutinib is clinically effective and tolerable as a monotherapy in real-world RR-CLL patients.

Type 2 diabetes mellitus compromises the survival of diffuse large B-cell lymphoma patients treated with (R)-CHOP - the PLRG report.

Comorbidities impair the prognosis of diffuse large B-cell lymphoma (DLBCL). Type 2 diabetes mellitus (DMT2) increases the risk of other comorbidities, e.g., heart failure (HF). Thus, we hypothesized that pre-existing DMT2 may negatively affect the outcome of DLBCL. To verify this, DLBCL patients treated with (R)-CHOP were enrolled. 469 patients were eligible, with a median age of 57 years; 356 patients had advanced-stage DLBCL. 126 patients had high-intermediate and 83 high-risk international prognostic index (IPI). Seventy-six patients had DMT2, 46 HF; 26 patients suffered from both DMT2 and HF. In the analyzed group DMT2 or HF significantly shortened overall survival (OS) and progression free survival (PFS): the 5-year OS for patients with DMT2 was 64% vs 79% and for those with HF: 49% vs 79%. The 5-year PFS for DMT2 was 50.6% vs 62.5% and for HF 39.4% vs 63.2%. The relapse/progression incidence was comparable between groups; the non-relapse/progression mortality (NRPM) was significantly higher solely in DMT2 patients (5-year NRPM 22.5% vs 8.4%). The risk of death was higher in patients with higher IPI (HR = 1.85) and with DMT2 (HR = 1.87). To conclude, pre-existing DMT2, in addition to a higher IPI and HF, was a negative predictor for OS and PFS.

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.

Acute decompensated heart failure as a reason of premature chemotherapy discontinuation may be independent of a lifetime doxorubicin dose in lymphoma patients with cardiovascular disorders.

BACKGROUND: Algorithm of anthracycline-based chemotherapy with favourable cardio-oncological outcome should be clearly re-defined for lymphoma patients with significant pre-existing cardiovascular diseases. A clinical benefit of liposomal forms of anthracycline is still debatable. METHODS: Polish registry included observations of 138 lymphoma patients with concomitant cardiovascular disorders who received liposomal doxorubicin as cardioprotective alternative of conventional form. It was created to analyse the importance of a strategy of administration of conventional/liposomal doxorubicin and a lifetime doxorubicin dose for development of acute decompensated heart failure (ADHF) as a reason of premature chemotherapy discontinuation. RESULTS: ADHF was the cause of premature termination of chemotherapy only in 11 patients (7.97%). The five new episodes of ADHF related to liposomal doxorubicin were recorded in subgroup of 70 patients with pre-existing heart failure (7.14%). There was the similar incidence of ADHF when liposomal doxorubicin was applied after conventional form in dose 200mg/m2 or if earlier signs of iatrogenic myocardial damage was recognised: 5 cases in subgroup of 51 patients with baseline cardiovascular risk factors (9.8%). ADHF was observed in one of 17 patients (5.88%) receiving liposomal doxorubicin as second line chemotherapy after first line with conventional doxorubicin. Consequently throughout the study group ADHF didn't depend on the total cumulative dose of all types of doxorubicin: OR=0.85; 95%CI: 0.66-1.10; p=0.22 for each 50mg/m2. CONCLUSION: The schedule of administration of conventional/liposomal doxorubicin can decide that lifetime combined doses of anthracyclines become insignificant for ADHF occurrence and premature discontinuation of chemotherapy in lymphoma patients with pre-existing cardiovascular disturbances.

Polish experience of lenalidomide in the treatment of lower risk myelodysplastic syndrome with isolated del(5q).

BACKGROUND: Lenalidomide has been approved for the treatment of lower-risk myelodysplastic syndrome (MDS) with 5q deletion (del(5q)). We present for the first time a retrospective analysis of low-risk MDS with isolated del5q treated with lenalidomide, outside the clinical trials. METHODS: 36 red blood cell (RBC) transfusion-dependent patients have been included in the study. Patients received lenalidomide 10 mg/day on days 1-21 of 28-day cycles. RESULTS: 91.7 % of patients responded to lenalidomide treatment: 72.2 % achieved erythroid response, 19.4 % achieved minor erythroid response and 8.4 % of patients did not respond to treatment. Response depended on number of previous treatment lines (p = 0.0101), International Prognostic System Score (IPSS; p = 0.0067) and RBC transfusion frequency (p = 0.0139). Median duration of response was 16 months (range 6-60 months). Treatment was well tolerated. We observed hematological toxicity (grade 3 and 4): neutropenia in 16 (44.4 %) patients and thrombocytopenia in 9 (25 %) patients. Two patients (5.5 %) progressed to high-risk MDS and two subsequent progressed to acute myeloid leukemia. A Kaplan-Meier estimate for overall survival at 5 years in the study group was 79.0 ± 8.8 %. CONCLUSIONS: Lenalidomide in this group of patients was beneficial for the treatment of RBC transfusion-dependency with well-known safety profile.

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.

Gemcitabine-Based Treatment in Poor-Prognosis Patients with Relapsed and Refractory Hodgkin Lymphoma and Non-Hodgkin Lymphoma--a Multicenter Polish Experience.

BACKGROUND: The treatment of patients with relapsed or refractory Hodgkin lymphoma (HL) and non-Hodgkin lymphoma (NHL) remains challenging. Gemcitabine is a cytidine analog with a wide spectrum of antitumor activity. Gemcitabine treatment is widely used to treat patients with certain solid tumors and relapsed/refractory hematological malignancies. There are several reports indicating that this compound is active in lymphoid malignancies. In patients with relapsed or refractory HL and NHL, gemcitabine has demonstrated efficacy as a single agent and in combination with other cytostatics. OBJECTIVES: The aim of the study was to analyze the efficacy and toxicity of gemcitabine-based chemotherapy in patients with relapsed or refractory lymphomas. MATERIAL AND METHODS: The study evaluated 68 heavily pretreated patients with relapsed/refractory HL and NHL. The median age of the patients was 36 years. All the patients received gemcitabine-based chemotherapy (gemcitabine monotherapy or gemcitabine in combination with other cytostatics). RESULTS: The overall response rate was 46%. Complete response was achieved by 21% of the patients and partial response by 25%. Out of those who responded to gemcitabine treatment, 26 patients proceeded to autologous stem cell transplant. Toxicities connected with gemcitabine therapy occurred in 44% of the patients and included grade 3/4 neutropenia, thrombocytopenia and anemia. CONCLUSIONS: The results suggest that gemcitabine-based salvage chemotherapy is effective and well tolerated in patients with relapsed/refractory HL and NHL.

Premature cardiovascular mortality in lymphoma patients treated with (R)-CHOP regimen - a national multicenter study.

BACKGROUND: Premature cardiovascular mortality related to chemotherapy and occurred in lymphoma survivors before disease progression is one of significant clinical failure of modern hematology. The aim of this retrospective analysis was to evaluate early cardiovascular mortality and its predictors in patients treated with the (R)-CHOP regimen. METHODS: The study assessed 610 patients: 581 patients were treated with non-liposomal doxorubicin (cumulative dose of 337 ± 96 mg/m2), and 29 patients with liposomal non-pegylated doxorubicin (cumulative dose of 237 ± 126 mg/m2). Their present status, history of cardiovascular diseases and associated risk factors were recorded. RESULTS: The analysis identified 93 deaths (15.5%): 51 cases (55%) related to lymphoma disease progression and 28 (30%) to cardiovascular complications. Multivariate Cox analysis revealed history of previous heart diseases (HR=4.71; CI: 3.82-5.6; p<0.001), ECG rhythm abnormalities related to chemotherapy (HR=4,78; CI: 3.63-5.92; p=0,01), and lack of complete remission (HR=2.73; CI: 1.78-3.66; p=0.03), as the independent predictors for cardiovascular death. Neither decreased LVEF nor increasing cumulative dose of anthracyclines had a significant predictive value for cardiovascular prognosis. CONCLUSIONS: The study indicated that cardiovascular mortality in lymphoma patients treated with (R)-CHOP regimen is relatively high and ECG monitoring may be the most effective in cardiological risk assessment. The unfavorable outcome depended on lack of complete remission that seems to be a consequence of patients' individual susceptibility for cardiac events, which should become a purpose of further trials.

[Liposomal cytarabine in prophylaxis of the central nervous system involvement in rare aggresive lymphomas]. / Liposomalna cytarabina w profilaktyce zajEcia centralnego systemu nerwowego w rzadkich chloniakach agresywnych.

UNLABELLED: The involvement of central nervous system in the course of lymphoma is an adverse prognostic factor, therefore primary prevention is a standard of care of aggressive lymphoma subtypes. The aim of the paper is the safety and efficiency, retrospective analysis of liposomal cytarabine used profilactically in patients with rare aggressive lymphomas. MATERIALS AND METHODS: In the analysis we included 19 patients with aggressive lymphomas: LBL (lymphoblastic lymphoma), BL (Burkitt lymphoma) and PTCL (peripheral T- cell lymphoma) from three PLRG (Polish Lymphoma Research Group) centers, who received liposomal cytarabine as primary prevention of central nervous system involvement. All the included patients had a high risk of CNS due to histological subtype (10 patients with LBL, 4 patients with BL), the specific location of the disease (N=3) or the presence of at least 2 risk factors for CNS involvement (elevated LDH, IPI 3-5 or involvement of at least 2 extranodal sites, N = 16). In this group, 18 patients were subjected to prophylaxis during the 1-st line therapy and one after relapse. None of the patients had symptoms of central nervous system involvement at the time of diagnosis. The median age was 43 years (the range of 20-60 years). In this group there were 14 males (73.68%) and 5 females (26.32%). The patients were treated with liposomal cytarabine every 2 to 4 weeks during the systemic chemotherapy. The median number of cytarabine doses was 2 (the range of 1-5). RESULTS: Liposomal cytarabine was well-tolerated. 63.1% of patients had transient side effects (nausea, vomiting, fever, dizziness) in grade 1-2, 5.2% of patients experienced a more severe headache (grade 3). During the average follow-up of 18 months, 50% of patients died and 27.7% of systemic recurrences were noted. Only one patient had a relapse in the CSN con comitant with a systemic recurrence. CONCLUSIONS: Lipo somal cytarabine is well-tolerated and effective medicine used in the prevention of CNS relapse in patients with ag gressive lymphoma subtypes.

Sclerosing angiomatoid nodular transformation of the spleen treated by laparoscopic partial splenectomy.

The authors describe a case of sclerosing angiomatoid nodular transformation (SANT) of the spleen treated at the 2(nd) Department of Surgery, Jagiellonian University, Medical College. The patient was a 23-year-old woman. Clinically she presented with 2-year history of recurrent mild fever, diffuse joint pain, abdominal discomfort and iron deficiency anaemia of chronic disease. The laboratory tests revealed a non-characteristic chronic inflammatory response. A splenic solid lesion 9 cm in diameter was found on abdominal computed tomography. The patient underwent uneventful laparoscopic resection of the upper half of the splenic parenchyma. The resected tumour showed characteristic histological and immunophenotypical findings of SANT as previously described in the literature. In long-term follow-up, improvement of preoperative symptoms and abnormalities in the blood tests was documented.

[IgA multiple myeloma with adverse prognostic factors--a case report]. / Szpiczak mnogi IgA z niekorzystnymi czynnikami rokowniczymi--opis przypadku.

IgA multiple myeloma is the second most frequent variant of multiple myeloma. The median survival is about 3 years and depends on presence, or not, certain prognostic factors. Cytogenetic status has become the most important of them. The presence of the chromosome 13 deletion is an independent adverse prognostic marker in multiple myeloma and is associated with specific biological features. Patients with the chromosome 13 alterations are less likely to respond to treatment and have a shorter median overall survival. We present a case of IgA multiple myeloma, which was even resistant to new therapeutic strategies (thalidomide, bortezomib).