Gastric MALT Lymphoma: A 8-Year Experience.

Gastric mucosa-associated lymphoid tissue non-Hodgkin lymphoma (gMALT NHL) is the second most common gastrointestinal lymphoma (50% of all gastric lymphomas), being closely associated with Helicobacter pylori infection, justifying that antibiotic therapy is effective in over 75% of all cases. This is a retrospective study analyzing all adult gMALT NHL cases diagnosed and treated in a single center for 8 years, focusing on demographic features, treatment outcomes, and survival analysis. Sixty patients with a median age of 61 years (53.3% female gender) were analyzed. Most of the cases had localized disease (66.7% were Lugano stage I) and had low IPI scores (median: 1). There was a high prevalence of Helicobacter pylori infection (68.3%). Nearly 97% of the cases received treatment for the disease, a median of one line; 55% of the patients treated endured complete response after first-line therapy (mostly antibiotics). Median overall survival time and median progression-free survival time were not reached. The mean follow-up time was 81.8 months (95% CI: [73.3-90.3]). Thirty-six patients (60%) achieved a 3-year follow-up time; the mortality rate was 15% at the end of the study. Age superior to 65 years and transformation into DLBCL were statistically significant negative prognostic markers for survival in this study (p = 0.006 and p = 0.033, respectively). Our study confirms that gMALT NHL is an indolent disease with long-term survival. Many patients, however, are exposed to several treatment lines along their disease course.

Gastric Diffuse Large B-Cell Lymphoma: A Single-Center 9-Year Experience.

Gastric diffuse large B cell lymphoma (DLBCL) represents the majority of all gastric lymphomas. We report a series of gastric DLBCL diagnosed and treated in a single center, between 2010 and 2018 (included). We retrospectively analyzed the population demographic features, treatment outcomes and survival. One-hundred-and-one patients were studied, 50.5% males and median age of 64 years [23-94]. Lugano staging was I in 16.8%, II1 in 20.8%, II2 in 10.9%, IIE in 13.9% and IV in 34.7% of cases. Twenty percent had Helicobacter pylori infection. R-CHOP-like therapy was used as first line in 96.9% of the patients. A complete response was achieved in 80% after first line therapy. At 3-years of follow-up (FU), 54% were in complete remission. The mean FU time was 73.6 months. Median overall survival and median progression free survival were not reached. We identified seven factors with negative impact in survival: age above 65 years-old (p < 0.01), ECOG 2-3 (p < 0.01), B symptoms (p = 0.001), bulky disease (p = 0.003), IPI 3-4 (p = 0.001), more than 3 treatment lines (p < 0.01), absence of response to first line treatment (p < 0.01). This study demonstrates that gastric DLBCL is a potentially curable disease with R-CHOP-like therapy, entailing long term survival and comparing well with other published series.

Discontinuation of tyrosine kinase inhibitors in CML patients in real-world clinical practice at a single institution.

BACKGROUND: Most patients with chronic myeloid leukemia (CML) treated with tyrosine kinase inhibitors (TKIs) will relapse if treatment is withdrawn, but various trials have recently demonstrated that a significant proportion of patients who achieved a stable and deep molecular response (DMR) can stop therapy without relapsing. However, most information on treatment cessation was obtained from clinical trials with strict recruiting criteria. METHODS: We evaluated the outcome of 25 patients with CML that discontinued TKI therapy in our institute in real-world clinical practice. RESULTS: Of the 25 patients, 76% discontinued therapy in sustained deep molecular response (SDMR) and 24% were in unsustained DMR (UDMR). Discontinuation of therapy due to adverse effects was observed in 5 and 50% of the patients in the SDMR and UDMR groups, respectively. After TKI discontinuation, patients were followed for a median of 24 months. At the time of this analysis, 56% patients had a molecular relapse after a median of 4 months. SDMR and longer treatment duration were associated with lower probability of molecular relapse: 25% in SDMR patients with TKI treatment > 96 months and 85% in UDMR patients with TKI treatment ≤96 months. All relapsed patients promptly resumed TKI therapy and regained at least major molecular response (MMR). CONCLUSIONS: Our results suggest that TKI discontinuation is safe outside clinical trials and particularly effective in CML patients who are in SDMR with longer TKI treatment duration.

Southwestern Oncology Group pretreatment risk criteria as predictive or prognostic factors in acute myeloid leukemia.

Acute myeloid leukemia (AML) is a clonal hematological malignant condition and the implications of pretreatment risk criteria as predictive or prognostic factors are constantly under evaluation. With this study, the authors' intent was to characterize AML patients and to evaluate the clinical outcome associated with Southwestern Oncology Group (SWOG) coding pretreatment risk criteria/cytogenetic score. Between 2002 and 2010, 225 patients were diagnosed with AML at the Portuguese Institute of Oncology (Porto, Portugal). From this patient group, 128 patients aged <65 years were selected. The patients were treated using a combination of cytarabine and anthracycline, with the addition of cyclosporine when bone marrow dysplasia was observed. A median survival of 24 months was observed in this group. The patients were divided in subgroups according to the SWOG pretreatment risk criteria. We observed a statistically significant association of non-favorable SWOG coding with female gender [P=0.025; risk ratio (RR)=3.632, 95% confidence interval (CI): 1.113-11.852], indication for allogeneic bone marrow transplantation (P=0.023, RR=1.317, 95% CI: 1.184-1.465), complete response achievement (P=0.013, RR=1.385, 95% CI: 11.232-1.556) and relapse (P=0.048, RR=3.181, 95% CI: 10.966-10.478). Furthermore, SWOG pretreatment risk criteria also significantly affected global overall survival (OS; P=0.003) and OS at 5 years (P=0.001). A multivariate Cox regression analysis supported response to induction therapy (3-year OS: P=0.011, RR=0.385, 95% CI: 10.184-0.806; 5-year OS: P=0.012, RR=0.388, 95% CI: 10.597-1.994), consolidation (3-year OS: P=0.005, RR=0.328, 95% CI: 0.150-0.720; 5-year OS: P=0.002, RR=0.308, 95% CI: 0.144-0.657) and the diagnosis of therapy-related aml (3-year OS: P=0.016, RR=2.756, 95% CI: 0.486-1.281; 5-year OS: P=0.031, RR=2.369, 95% CI: 1.081-5.189) as prognostic factors, but this was not confirmed for SWOG pretreatment risk criteria. Therefore, we concluded that the reproducibility of the application of the SWOG pretreatment risk criteria may not be available as a prognostic factor in every acute leukemia population. However, its application as a predictive factor of response has been confirmed in our population.

Effect of therapy-related acute myeloid leukemia on the outcome of patients with acute myeloid leukemia.

Therapy-related acute myeloid leukemia (t-AML) is a rare and almost always fatal late side effect of antineoplastic treatment involving chemotherapy, radiotherapy or the two combined. The present retrospective study intended to characterize t-AML patients that were diagnosed and treated in a single referral to an oncological institution in North Portugal. Over the past 10 years, 231 cases of AML were diagnosed and treated at the Portuguese Institute of Oncology of Porto, of which 38 t-AML cases were identified. Data regarding the patient demographics, primary diagnosis and treatment, age at onset of therapy-related myeloid neoplasm, latency time of the neoplasm, cytogenetic characteristics, AML therapy and outcome were collected from medical records. A previous diagnosis with solid tumors was present in 28 patients, and 10 patients possessed a history of hematological conditions, all a lymphoproliferative disorder. Breast cancer was the most frequent solid tumor identified (39.5% of all solid tumors diagnosed). The mean latency time was 3 years. In the present study, t-AML patients were older (P<0.001) and more frequently carried cytogenetic abnormalities (P=0.009) compared with de novo AML patients. The overall survival time was observed to be significantly poorer among individuals with t-AML (P<0.001). However, in younger patients (age, <50 years) there was no difference between the overall survival time of patients with t-AML and those with de novo AML (P=0.983). Additionally, patients with promyelocytic leukemia possess a good prognosis, even when AML occurs as a secondary event (P=0.98). To the best of our knowledge, the present study is the first to evaluate t-AML in Portugal and the results are consistent with the data published previously in other populations. The present study concludes that although t-AML demonstrates a poor prognosis, this is not observed among younger patients or promyelocytic leukemia patients.

Mucositis care in acute leukemia and non-Hodgkin lymphoma patients undergoing high-dose chemotherapy.

PURPOSE: This study intends to provide new insights into the incidence and care of mucositis by the epidemiological characterization of patients with hematological malignancy treated at our institution. It also aims to understand the effectiveness of several treatments used. METHODS: This is a longitudinal observational single-center study-convenience sample-which includes malignant hematologic inpatients submitted to high-dose CT from February to August 2012. We registered epidemiological data, diagnosis, oral mucositis daily questionnaire (OMDQ), World Health Organization (WHO) oral toxicity scale, and supportive medications used for mucositis. RESULTS: We evaluated 30 patients who had 73 episodes of hospitalization, having recorded the development of mucositis in 21.9 % (n = 16) episodes (22 patients with acute leukemia (AL) and 8 patients with non-Hodgkin lymphoma (NHL)). Grades 3-4 mucositis was reported in 4.1 % of the total episodes. The results of OMDQ showed some limitations in the quality of life, of patients with mucositis, related with the ability to eat and drink due to mouth pain (p < 0.001). In patients with NHL and AL, neutropenia entails an increased risk of mucositis (p < 0.001). Patients who did not initiate early prophylaxis with conservative measures developed mucositis earlier (p < 0.05). CONCLUSIONS: The incidence of mucositis is high, being reported mainly in AL patients, with limitations in quality of life. Grade 4 neutropenia increases mucositis risk. Early prophylaxis with basic oral care may delay mucositis. Further studies are crucial to characterize mucositis epidemiology, physiopathology, and its management.

Genetic and clinical characterization of 45 acute leukemia patients with MLL gene rearrangements from a single institution.

Chromosomal rearrangements affecting the MLL gene are associated with high-risk pediatric, adult and therapy-associated acute leukemia. In this study, conventional cytogenetic, fluorescence in situ hybridization, and molecular genetic studies were used to characterize the type and frequency of MLL rearrangements in a consecutive series of 45 Portuguese patients with MLL-related leukemia treated in a single institution between 1998 and 2011. In the group of patients with acute lymphoblastic leukemia and an identified MLL fusion partner, 47% showed the presence of an MLL-AFF1 fusion, as a result of a t(4;11). In the remaining cases, a MLL-MLLT3 (27%), a MLL-MLLT1 (20%), or MLL-MLLT4 (7%) rearrangement was found. The most frequent rearrangement found in patients with acute myeloid leukemia was the MLL-MLLT3 fusion (42%), followed by MLL-MLLT10 (23%), MLL-MLLT1 (8%), MLL-ELL (8%), MLL-MLLT4 (4%), and MLL-MLLT11 (4%). In three patients, fusions involving MLL and a septin family gene (SEPT2, SEPT6, and SEPT9), were identified. The most frequently identified chromosomal rearrangements were reciprocal translocations, but insertions and deletions, some cryptic, were also observed. In our series, patients with MLL rearrangements were shown to have a poor prognosis, regardless of leukemia subtype. Interestingly, children with 1 year or less showed a statistically significant better overall survival when compared with both older children and adults. The use of a combined strategy in the initial genetic evaluation of acute leukemia patients allowed us to characterize the pattern of MLL rearrangements in our institution, including our previous discovery of two novel MLL fusion partners, the SEPT2 and CT45A2 genes, and a very rare MLL-MLLT4 fusion variant.