Dario Marino

Diagnostic and prognostic role of alpha-fetoprotein in hepatocellular carcinoma: both or neither?

BACKGROUND:The clinical usefulness of α-fetoprotein (AFP) in hepatocellular carcinoma (HCC) management is debatable.OBJECTIVES:To assess, in a large multi-centric survey, diagnostic and prognostic reliability of AFP, predictive factors, and any correlation with the tumor immunophenotype.METHODS:A total of 1,158 patients with HCC were analyzed with reference to serum AFP levels at diagnosis. We evaluated: HCC grading, histotype, and size; Okuda, tumor–nodes–metastases (TNM), and Child-Pugh scores; liver function, symptoms, presence of metastases or portal thrombosis, etiology, survival, and treatment. In 66 patients with histological diagnosis, the pathologists evaluated p53 overexpression, MIB 1 labeling index, BCL-2 positive cells (index of apoptosis), and CD44 (adhesion molecule) positivity.RESULTS:Patients were divided into three AFP groups: normal (<20 ng/mL) [46%], elevated (21–400 ng/mL) [36%], and diagnostic (>400 ng/mL) [18%]. Statistical correlations were significant for: weight loss (P = 0.0056), pain (P = 0.0025), Child-Pugh score (P = 0.001), tumor size, Okudas and TNM stages, metastases, thrombosis, type of treatment (all p < 0.0001), and female sex (p < 0.004). AFP correlated with survival overall, in patients untreated, transplanted, or undergoing locoregional treatments; but not in those surgically treated. In the discriminant analysis, the related variables were size, female sex, Child-Pugh score, TNM staging (steps 1–4). When using the receiver operating characteristic curve, the prognostic reliability of AFP was limited with area under the curve of 0.59. Finally, patients with low expression of BCL2 had high AFP levels (p < 0.05). AFP positively correlated with Edmonson score (p < 0.0001).CONCLUSION:The evaluation of this large series of HCC patients allowed us to: confirm the low sensitivity (54%) of AFP in the diagnosis of HCC and its prognostic value, albeit limited, being tumor size, female sex (intriguingly enough), Child-Pugh score, and TNM staging independent predictors.

Percutaneous radiofrequency thermal ablation for hepatocellular carcinoma

Radiofrequency thermal ablation is the first therapeutic option in percutaneous treatment of hepatocellular carcinoma but data on its long‐term efficacy and safety are not conclusive.

Intrathecal chemotherapy in lymphomatous meningitis

Central Nervous System (CNS) involvement in lymphoma can occur whether at diagnosis or, more often, at the progression or recurrence of disease and the most frequent clinical manifestation is lymphomatous meningitis (LM). The first risk factor for LM development is the histotype, with the highest incidence for highly aggressive non-Hodgkins lymphomas (NHL) such as Burkitts lymphoma (BL) and lymphoblastic lymphoma/acute lymphoblastic leukemia (LBL/ALL) and the lowest for indolent NHL. LM prophylaxis in aggressive NHL (other than BL and LBL/ALL) is a much debated question, because the identification of specific risk factors remains controversial. Moreover, there is not a consensus if the LM prophylaxis should consist of systemic chemotherapy (CT), intrathecal (i.t.) CT or both. In case of LM, the i.t. CT has a key role, but there is not a consensus on treatment schedule. Newer intensified regimens and rituximab lead to reconsider the whole approach to LM.

Fatal HBV-related liver failure during lamivudine therapy in a patient with non-Hodgkin's lymphoma.

.Wereportthecaseofa59-year-oldmanadmittedtoourdepartmenton2August2006withfever,fatigueandjaundice.InDecember2005thepatientwasfirstdiagno -sedwithstageIIBbulkydiffuselargeBcelllymphoma,CD20+withanaaIPIof1.Atthetimeofdiagnosis,hehadsplenomegalyandhepatomegaly;laparoscopicspleenandliverbiopsyresultedinahistologicaldiagnosisofsplenicinfiltrationofnon-Hodgkin’slymphoma(NHL)inacontextofchronichepatitis(withmildactivity,gradeG2),suggestiveofviralinfection.Stagingwascompletedwiththoracicandabdomi-nalCTthatevidencedaspleniclesionof13x14x16cmalongwithliverinvolvementwithsmallnodulesinthefourthsegmentandseveralmesenteric,hepatichilumandparaaorticinvolvedlymphnodes.SerologyrevealedthepatienttobeachronicHBVcarrier(HbsAgpositive).ThepatientwasHbeAgnegativeandanti-HBcpositivewithahighHBVDNAtiterof5,017,954IU/mL.CoexistinghepatitisCorhepatitisDviruswasexcludedbeforechemotherapy.Thelevelofaspartateaminotransferase(AST)was60U/L(normal10-45U/L),alanineaminotransferase(ALT)was50U/L(normal10-50U/L),whiletheremainingroutinebiochemicalexaminationsincludingbiliru -bin,albumin,plateletandWBCcountswerewithinnormalranges.ViralsequencingoftheHBVstraindidnotrevealthepresenceofmutationsassociatedwithresistanceto lamivudine. Lamivudine treatment 100 mg/day was started together with achemotherapyregimenconsistingofcyclophosphamide,doxorubicin,vincristine,prednisoneandrituximab(CHOP-R)givenfor8cycles.PETCTafterchemotherapyshowedremissionoftheneoplasticdiseasebutasplenicresidual,sothepatientwasgivenadditionalradiotherapytothesplenicarea(lastcourseon7July2006).Athisadmissiontoourdepartment,thepatient’shematologicalpanelwasnormalbutliverbiochemistryrevealedserumASTtobe3,878U/L,ALT4,364U/L,totalbilirubin137.1 mol/L,alkalinephosphatase138U/L,andalbumin35.5g/L.Othernonviralcausesofacutehepatitiswereexcluded.HBVDNAwas95,528IU/mL.Thepatientwasstillonlamivudinetreatment.ViralsequencingoftheHBVstrainrevealedthepresenceofacombinedL180MandM204Imutation,whichisassociatedwithre -si tan ce o lmv ud

Acute promyelocytic leukemia after Stanford V plus radiotherapy for advanced Hodgkin lymphoma

ABVD chemotherapy (adriamycin, bleomycin, vinblastine, dacarbazine) is considered the standard treatment for advanced Hodgkin lymphoma. However, pulmonary and cardiac toxicity rates due to bleomycin and adriamycin, increased by mediastinal irradiation, and treatment failures (about 25%) prompted the development of new regimens, including BEACOPP [1] and Stanford V [2]. The Stanford V regimen, followed by consolidation involved-field (IF) radiotherapy (RT) was designed to maximise dose intensity reducing the total dose of adriamycin (to 150 mg/m), bleomycin (to 30 U/m), nitrogen mustard (to 18 mg/m), avoiding procarbazine. Preliminary reports showed that the Stanford V regimen with RT was well tolerated and effective for bulky, advanced-stage Hodgkin lymphoma [2]. These results were confirmed by several studies [3,4], the latest one performed by Nebraska Lymphoma Study Group [5]. The long-term survivors from Hodgkin lymphoma are at risk for second malignancies (solid tumors, leukemia and non-Hodgkin lymphoma) that account for the majority of late deaths [1]. When compared with the general population, the risk of myelodysplasia and secondary acute leukemia is increased 10to 80-fold and it appears to be related to the total dose of alkylating agents and DNA topoisomerase-II inhibitors. The cumulative risk of secondary leukemia varies from 6 to 9% after MOPP regimen; 2.5% after the escalated BEACOPP regimen and 0.5% after the standard ABVD. We report a case of acute leukemia in a 28-year-old woman who was treated for Hodgkin lymphoma with Stanford V regimen followed by radiotherapy. In September 1999, the patient was first diagnosed with a IIB, non bulky, subdiaphragmatic, mixed cellularity Hodgkin lymphoma. Bone marrow examination was normal. In October 1999, Stanford V chemotherapy was administered for 10 weeks instead of the planned 12 weeks followed by subdiaphragmatic involved-field radiotherapy; chemotherapy was stopped earlier because of grade 4 constipation. During the neutropenic phases, the patient received G-CSF. The whole treatment was completed in May 2000. The patient achieved a complete remission and enjoyed good health for 4 years. In September 2004, she was admitted to the Department of Hematology with a disseminated intravascular coagulation. Hemoglobin was 97 g/L, white blood cell count was 86.36 10/L, platelet count 116 10/L, LDH 698 U/L. The diagnosis of Acute Promyelocytic Leukemia (APL) was established upon examination of both peripheral blood and bone marrow smears. The blasts had the following

A Comparison of the Conditioning Regimens BEAM and FEAM for Autologous Hematopoietic Stem Cell Transplantation in Lymphoma: An Observational Study on 1038 Patients From Fondazione Italiana Linfomi

BEAM (carmustine [bis-chloroethylnitrosourea (BCNU)]-etoposide-cytarabine-melphalan) chemotherapy is the standard conditioning regimen for autologous stem cell transplantation (ASCT) in lymphomas. Owing to BCNU shortages, many centers switched to fotemustine-substituted BEAM (FEAM), lacking proof of equivalence. We conducted a retrospective cohort study in 18 Italian centers to compare the safety and efficacy of BEAM and FEAM regimens for ASCT in lymphomas performed from 2008 to 2015. We enrolled 1038 patients (BEAM = 607, FEAM = 431), of which 27% had Hodgkin lymphoma (HL), 14% indolent non-Hodgkin lymphoma (NHL), and 59% aggressive NHL. Baseline characteristics including age, sex, stage, B-symptoms, extranodal involvement, previous treatments, response before ASCT, and overall conditioning intensity were well balanced between BEAM and FEAM; notable exceptions were median ASCT year (BEAM = 2011 versus FEAM = 2013, P < .001), Sorror score ≥3 (BEAM = 15% versus FEAM = 10%, P = .017), and radiotherapy use (BEAM = 18% versus FEAM = 10%, P < .001). FEAM conditioning resulted in higher rates of gastrointestinal and infectious toxicities, including severe oral mucositis grade ≥3 (BEAM = 31% versus FEAM = 44%, P < .001), and sepsis from Gram-negative bacteria (mean isolates/patient: BEAM = .1 versus FEAM = .19, P < .001). Response status at day 100 post-ASCT (overall response: BEAM = 91% versus FEAM = 88%, P = .42), 2-year overall survival (83.9%; 95% confidence interval [CI], 81.5% to 86.1%) and progression-free survival (70.3%; 95% CI, 67.4% to 73.1%) were not different in the two groups. Mortality from infection was higher in the FEAM group (subhazard ratio, 1.99; 95% CI, 1.02 to 3.88; P = .04). BEAM and FEAM do not appear different in terms of survival and disease control. However, due to concerns of higher toxicity, fotemustine substitution in BEAM does not seem justified, if not for easier supply.

Post Transplant Lymphoproliferative Disorders After Liver Transplantation

Post-transplant lymphoproliferative disorder (PTLD) is a clearly recognized and potentially life threatening complication after solid organ or bone marrow transplantation. It comprises a spectrum of diseases ranging from infectious mononucleosis and lymphoid hyperplasia to highly aggressive lymphoma. The disease has increased clinical importance in view of the constantly rising number of organ transplant recipients and the development of more potent and specific immunosuppressive drugs.