Infectious aetiology of marginal zone lymphoma and role of anti-infective therapy

Marginal zone lymphomas have been associated with several infectious agents covering both viral and bacterial pathogens and in some cases a clear aetiological role has been established. Pathogenetic mechanisms are currently not completely understood. However, the role of chronic stimulation of the host immune response with persistent lymphocyte activation represents the most convincing explanation for lymphoproliferation. Gastric MALT lymphoma is strictly associated with Helicobacter pylori infection and various eradicating protocols, developed due to increasing antibiotic resistance, represent the first line therapy for gastric MALT. The response rate to eradication is good with 80% of response at 1 year; this finding is also noteworthy because it recapitulates cancer cured only by the antibacterial approach and it satisfies the Koch postulates of causation, establishing a causative relationship between Hp and gastric MALT lymphoma. Patients with chronic HCV infection have 5 times higher risk to develop MZL, in particular, an association with splenic and nodal MZL has been shown in several studies. Moreover, there is evidence of lymphoma regression after antiviral therapy with interferon+ribavirin, thus raising hope that newly available drugs, extremely efficient against HCV replication, could improve outcome also in HCV-driven lymphomas. Another case-study are represented by those rare cases of MZL localized to orbital fat and eye conjunctivas that have been associated with Chlamydophila psittaci infection carried by birds. Efficacy of antibacterial therapy against C. psittaci are conflicting and generally poorer than gastric MALT. Finally, some case reports will cover the relationship between primary cutaneous B-cell Lymphomas and Borrelia Burgdorferi

Bit-flipping Decoder Failure Rate Estimation for (v,w)-regular Codes

Providing closed form estimates of the decoding failure rate of iterative decoder for low- and moderate-density parity check codes has attracted significant interest in the research community over the years. This interest has raised recently due to the use of iterative decoders in post-quantum cryptosystems, where the desired decoding failure rates are impossible to estimate via Monte Carlo simulations. In this work, we propose a new technique to provide accurate estimates of the DFR of a two-iterations (parallel) bit flipping decoder, which is also employable for cryptographic purposes. In doing so, we successfully tackle the estimation of the bit flipping probabilities at the second decoder iteration, and provide a fitting estimate for the syndrome weight distribution at the first iteration. We numerically validate our results, providing comparisons of the modeled and simulated weight of the syndrome, incorrectly-guessed error bit distribution at the end of the first iteration, and two-iteration Decoding Failure Rates (DFR), both in the floor and waterfall regime for simulatable codes. Finally, we apply our method to estimate the DFR of LEDAcrypt parameters, showing improvements by factors larger than $2^{70}$ (for NIST category $1$) with respect to the previous estimation techniques. This allows for a $\approx 20$% shortening in public key and ciphertext sizes, at no security loss, making the smallest ciphertext for NIST category $1$ only $6$% larger than the one of BIKE. We note that the analyzed two-iterations decoder is applicable in BIKE, where swapping it with the current black-gray decoder (and adjusting the parameters) would provide strong IND-CCA$2$ guarantees.Comment: Fixed typos: derivation of a from a=(x-y+v)/2 to a=(y-x+v)/2; replaced (x-y+v)/2 with (y-x+v)/2 and (x-y+v-1)/2 with (y-x+v-1)/2 in rho(x,y,l); replaced d+ with d- in the def. of delta-(d-); replaced epsilon01-l with l in zeta(tc,l,epsilon01) and epsilon11-l with l in lambda(tc,l,epsilon11) (apart from the def.s); explicited epsilon01 and epsilon11 in zeta and chi_od

Bit-flipping Decoder Failure Rate Estimation for (v,w)-regular Codes

Providing closed form estimates of the Decoding Failure Rates (DFR) of iterative decoder for low- and moderate-density parity check codes has attracted significant interest in the research community over the years. This interest has raised due to the use of iterative decoders in post-quantum cryptosystems, where the desired DFRs are impossible to estimate via Monte Carlo simulations. In this work, we propose a new technique to provide accurate estimates of the DFR of a two-iterations (parallel) bit-flipping decoder, which is also employable for cryptographic purposes. In doing so, we successfully tackle the estimation of the bit-flipping probabilities at the first and second decoder iteration, and provide a fitting estimate for the syndrome weight distribution. We numerically validate our results, providing comparisons of the modeled and simulated weight of the syndrome, incorrectly-guessed error bit distribution at the end of the first iteration, and two-iteration DFR, both in the floor and waterfall regime. Finally, we apply our method to estimate the DFR of LEDAcrypt, a post-quantum cryptosystem, improving by factors larger than 2^{70}, with respect to the previous estimation techniques

Bendamustine in combination with gemcitabine and vinorelbine is an effective regimen as induction chemotherapy before autologous stem-cell transplantation for relapsed or refractory Hodgkin lymphoma: Final results of a multicenter phase II study

Purpose: This multicenter, open-label, phase II study evaluated the combination of bendamustine, gemcitabine, and vinorelbine (BeGEV) as induction therapy before autologous stem-cell transplantation (ASCT) in patients with relapsed or refractory Hodgkin lymphoma (HL). Patients and Methods: Patients with HL who were refractory to or had relapsed after one previous chemotherapy line were eligible. The primary end point was complete response (CR) rate after four cycles of therapy. Secondary end points were: overall response rate, stem-cell mobilization activity, and toxicity. Progression-free and overall survival were also evaluated. Results: In total, 59 patients were enrolled. After four cycles of therapy, 43 patients (73%) achieved CR, and six (10%) achieved partial response, for an overall response rate of 83%. The most common grade 3 to 4 nonhematologic toxicities included febrile neutropenia (n = 7) and infection (n = 4). Regarding hematologic toxicities, grade 3 to 4 thrombocytopenia and neutropenia were each experienced by eight patients (13.5%). CD34+ cells were successfully harvested in 55 of 57 evaluable patients, and 43 of 49 responding patients underwent ASCT. With a median follow-up of 29 months, the 2-year progression-free and overall survival rates for the total population were 62.2% and 77.6%, respectively. The same figures for patients undergoing autograft were 80.8% and 89.3%, respectively. Conclusion: This phase II study demonstrates that BeGEV is an effective salvage regimen able to induce CR in a high proportion of patients with relapsed or refractory HL before ASCT. These data provide a strong rationale for further development of the BeGEV regimen

Designing QC-MDPC Public Key Encryption Schemes with Niederreiter\u27s Construction and a Bit Flipping Decoder with Bounded DFR

Post-quantum public key encryption (PKE) schemes employing Quasi-cyclic (QC) sparse parity-check matrix codes are enjoying significant success, thanks to their good performance profile and reduction to believed-hard problems from coding theory. However, using QC sparse parity-check matrix codes (i.e., QC-MDPC/LDPC codes) comes with a significant challenge: determining in closed-form their decoding failure rate (DFR), as decoding failures are known to leak information on the private key. Furthermore, there is no formal proof that changing the (constant) rate of the employed codes does not change the nature of the underlying hard problem, nor of the hardness of decoding random QC codes is formally related to the decoding hardness of random codes. In this work, we address and solve these challenges, providing a novel closed-form estimation of the decoding failure rate for three-iteration bit flipping decoders, and proving computational equivalences among the aforementioned problems. This allows us to design systematically a Niederreiter-style QC-MDPC PKE, enjoying the flexibility granted by freely choosing the code rate, and the significant improvements in tightness of our DFR bound. We report a $2\times$ improvement in public key and ciphertext size w.r.t. the previous best cryptosystem design with DFR closed-form bounds, LEDAcrypt-KEM. Furthermore, we show that our PKE parameters yield $30$% smaller public key size and $2.6\times$ smaller ciphertexts w.r.t. HQC, which is the key encapsulation method employing a code based PKE, recently selected by the US NIST for standardization

90-yttrium-ibritumomab tiuxetan consolidation of fludarabine, mitoxantrone, rituximab in intermediate/high-risk follicular lymphoma: updated long-term results after a median follow-up of 7\ua0years

Radioimmunotherapy (RIT) after an induction phase with conventional chemoimmunotherapy became an attractive strategy of consolidation for patients with advanced follicular lymphoma: in particular, in many studies RIT was represented by yttrium-90-ibritumomab tiuxetan (90Y-IT). Independently by the different front-line treatment, updates on the long-term follow-up of these studies are needed because the disease course of follicular lymphoma is characterised by multiple relapses and progressively shorter durations of response. We report updated long-term efficacy and toxicity results of a multicenter phase II study on sequential treatment with four cycles of fludarabine, mitoxantrone, and rituximab followed by 90Y-IT as front-line therapy for untreated patients with intermediate/high-risk follicular lymphoma. With a median follow-up of 84 months, only 19/49 (38.8%) complete response patients relapsed, yielding an estimated long-term disease-free survival of 62.6%. The 7-year overall survival was 72.7%. Four (7.3%) second acute myeloid leukemia occurred, with a median time following RIT of 42 months. A relevant patients' responsiveness to subsequent therapies occurred: approximately 65% of relapsed patients obtained a good clinical response after the second-line treatment. These data represented the first evidence of a real role even in the long period of 90Y-IT after a fludarabine-containing regimen plus rituximab in the treatment of high-risk follicular lymphoma

Primary uterine localization of malt lymphoma: A case report and literature review

[No abstract available

Splenic marginal zone lymphoma: Prognostic factors, role of watch and wait policy, and other therapeutic approaches in the rituximab era

Splenic marginal zone lymphoma (SMZL) is an indolent lymphoma in which watch and wait (W&W) approach as well as splenectomy and chemo-immunotherapy are usually recommended. The role of the different approaches in relation to risk factors was evaluated. One hundred patients with SMZL were retrospectively studied. Median age was 65 years. HCV positivity was 3.1%. The 10-year overall-survival was 95.1% (CI: 90-100%). Sixty-two asymptomatic, low tumour burden patients were submitted to W&W. A low-risk group not requiring treatment was identified. Patients requiring treatment received splenectomy (36), chemotherapy-alone (27) and rituximab ± chemotherapy (16). In multivariate analysis, negative predictors for starting treatment were female-sex, splenomegaly, ECOG ≥ 1. Patients with low IIL-Score had a better 5-year TFT (24%). The median TFT of the W&W cohort was 58.5 months; at 10 years, 17% of patients were still on W&W. Splenectomy and rituximab ± chemotherapy showed similar results, while chemotherapy alone proved inferior. This real-life single-centre study of SMZL confirmed its very good prognosis with a survival likelihood overlapping that of general population. The prognostic role of IIL-Score was confirmed. The W&W approach allowed a median PFS longer than in follicular lymphoma. Finally, our data confirm the inferiority of chemotherapy compared to splenectomy and rituximab ± chemotherapy

Regression of a case of Multiple Myeloma with antiviral treatment in a patient with chronic HCV infection

AbstractWe report a case of a 54 year old patient with Multiple Myeloma (MM) and chronic HCV infection. In 2005 MM was diagnosed and a chemotherapy was prescribed. Before starting treatment a chronic HCV infection was found. When she came to our Institution for a second opinion, chemotherapy treatment was not considered immediately necessary so the patient was treated for the HCV chronic infection (Pegilated alpha-Interferon 180μg/week and Ribavirin 1000mg p.o./day). After one month of treatment she presented a reduction of Bence Jones protein (BJ) that further decreased in the following three months. The antiviral treatment was suspended after six months and a re-evaluation showed a complete viral response and a regression of MM. Sixty-eight months after the end of antiviral treatment the patient is asymptomatic and presents a condition compatible with an M-GUS. While the association between HCV infection and non-Hodgkin's lymphoma is consolidated and it is clearly demonstrated that antiviral treatment in these patients can induce a high proportion of partial and complete remission, a similar effect was never described in MM. The response obtained in our patient may suggest a possible a role of HCV in the pathogenesis of MM