Salvatore Perrone

Primary mediastinal lymphoma: diagnosis and treatment options

Primary mediastinal large B-cell lymphoma (PMBCL) is a unique B-cell lymphoma variant that arises from a putative thymic medulla B cell. It constitutes 2–4% of non-Hodgkin lymphomas and occurs most frequently in young females. PMBCL is characterized by a diffuse proliferation of medium-to-large B cells associated with sclerosis. Molecular analysis shows that PMBCL is a distinct entity compared to other types of diffuse large B-cell lymphomas. PMBCL is characterized by a locally invasive anterior mediastinal bulky mass. The combination of rituximab with CHOP/CHOP-like regimens followed by mediastinal radiation therapy (RT) is associated with a 5-year progression-free survival of 75–85%. However, the role of consolidation RT still remains uncertain. More intensive regimens, such as DA-EPOCH-R without mediastinal RT, have shown very promising results. The conclusive role of PET-CT scan requires prospective studies and there is hope that this may allow to de-escalate RT and accordingly yield reliable prognostic information.

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.

The immune reconstitution after an allogeneic stem cell transplant correlates with the risk of graft-versus-host disease and cytomegalovirus infection

Aim of the study was to correlate the clinical outcome of eighteen patients who have undergone an allogeneic stem cell transplant (SCT) with the concentration in the peripheral blood (PB) of lymphocyte subpopulations evaluated at 1 year from transplant. The occurrence of acute GVHD and CMV infection correlated with the concentration of Tregs in the PB; CMV infection also correlated with the content of NK cells. The obtained results document that the concentration of Tregs in the PB after an allogeneic SCT may protect from GVHD and from CMV infection; the potential anti-viral role of NK cells is confirmed.

Early onset of posterior reversible encephalopathy syndrome (PRES) during Cyclosporine-A infusion.

Posterior reversible encephalopathy syndrome (PRES) is an ncommon but distinctive clinico-radiologic entity characterized y headache, seizures, visual disturbance and altered mental funcion associated with reversible white matter edema affecting the osterior parietal and occipital lobes of the brain [1,2]. Etioloies of PRES include hypertension, cytotoxic medications, sepsis, reeclampsia or eclampsia and multiple organ dysfunction [3]. In he context of allogeneic stem cell transplantation (HSCT), severe eurotoxicity is reported in a substantial number of patients, being yclosporine-A (CSA) most frequently indicated as the medication esponsible for the neurological alterations [4–6].

Proven Epstein–Barr encephalitis with negative EBV‐DNA load in cerebrospinal fluid after allogeneic hematopoietic stem cell transplantation in a child with acute lymphoblastic leukemia

We report a case of EBV encephalitis in a seven‐yr‐old child with Ph+ ALL. Two months after an allogeneic HSCT from his HLA mismatched mother, the patient showed an altered sensorium, generalized seizures, and a left hemiparesis. Brain MRI demonstrated multiple lesions highly suggestive for viral encephalitis. Blood and CSF PCR analyses were negative for the most common viruses involved in immunocompromised patients including EBV. A cerebral biopsy was performed, which showed intense gliosis and perivascular lymphocytic cuffing. PCR analysis performed on brain tissue was positive only for the EBV genome, while extensive investigations for other viral infections were negative. The patients neurological symptoms rapidly worsened and he died two months later. This case report suggests that in patients presenting neurological and radiological signs of encephalitis after an HSCT, an EBV involvement should be considered, even in the absence of CSF and blood PCR virus detection.

How has treatment changed for blast phase chronic myeloid leukemia patients in the tyrosine kinase inhibitor era? A review of efficacy and safety

ABSTRACT Introduction: Management of chronic myeloid leukemia (CML) patients in advanced phases of disease has drastically changed since the introduction of tyrosine kinase inhibitors (TKIs) which provide tailored treatment strategies. Areas covered: In this review, efficacy data of different TKIs are reported and reviewed when used as single agent or in combination for the management of blast phase (BP) CML. Expert opinion: Although brilliant results were achieved, the outcome of BP patients did not change when TKIs were used as single agents. Newer strategies of association of TKI with intensified chemotherapy or new agents for different pathways are strongly needed as a bridge to possible allogeneic transplant.

Is pneumatosis intestinalis a contraindication to allogeneic hemopoietic stem cell transplantation

Pneumatosis intestinalis (PI) has been described as a possible complication after allogeneic stem cell transplantation (HSCT) due to graft-versus-host disease (GVHD) or infections. So far, no patient with a pre-existent PI who underwent HSCT has been reported. We describe the case of a patient with Alk-negative anaplastic large B-cell lymphoma (DLBCL anaplastic) and PI who successfully received a HSCT from an unrelated donor without complications. This case suggests that this gastrointestinal condition should not be considered an absolute contraindication for an allotransplant procedure. Correspondence to: Antonietta Ferretti, MD; Haematology, “Sapienza” University; Via Benevento, 6; Rome, Italy; Tel: +39 0649974777; E-mail: ferretti@bce.uniroma1.it

Reappraising the timing of transplant for indolent non-Hodgkin lymphomas

ABSTRACT Introduction: Indolent non-Hodgkin lymphomas (iNHL) remain incurable with standard approaches. The timing of autologous stem cell transplant (ASCT) is changing following the introduction of new drugs that can potentially defer the transplant, improved reduced intensity conditioning (RIC) and haploidentical allogeneic SCT (allo-SCT). Areas covered: The most relevant aspects concerning the role of hematopoietic stem cell transplantation in the management of iNHL are discussed. Literature search methodology included examination of PubMed index and meeting presentations. Expert commentary: ASCT is not currently employed as consolidation in first-line, being reserved to patients with refractory/relapsed disease. The curative potential of graft-versus-lymphoma (GVL) after RIC allo-SCT could be particularly beneficial in patients with iNHL relapsing after ASCT. This scenario could be modified in the near future by better definition of high-risk patients at diagnosis, by the improvement of minimal residual disease (MRD) evaluation and by the introduction of new drugs in the therapeutic algorithm.