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METHODS were divided according to the International Prognostic
Index (IPI) value and numbers of chemotherapeutic
Patients regimens as prognostic factors referred to OS and TTF.
From February 2006 to July 2014, 45 relapsed/
refractory DLBCLs patients treated with GDP-R at our Statistical analysis
Institution entered into the study. Eligibility criteria Before performing survival analysis, an exploration phase
were men or women aged > 18 years; documentation was carried out. Categorical data were described by frequency
of unresponsiveness disease according to the Cheson and percentage, whereas continuous data by mean, median,
criteria, after one or more chemotherapeutic regimens; and range.
[10]
absence of renal, hepatic, and respiratory failure; no
evidence of active infections; HIV-negativity; at least one Complete and partial response to chemotherapy
site of measurable disease; and written informed consent. CR and partial response (CR and PR, respectively, according
In particular, of a total of 45 studied patients, 37 (82%) to the Cheson criteria) in patients with more than 2 or 2
relapsed after achieving an initial complete response (CR), or < 2 chemotherapeutic regimens were assessed by using
while the remaining 8 patients (18%) were primary non- the Fisher exact test.
responders (primary refractory disease). Patient evaluation
included a full history and clinical examination, complete Survival analysis
serum biochemistry with dosage of lactate dehydrogenase The survival was expressed as mean, median, and range. The
(LDH) and β2-microglubulin, peripheral blood and bone endpoints studied included TTF (defined as the time from the
marrow immunophenotyping, bone marrow biopsy, bone beginning of treatment to further disease progression, relapse,
marrow molecular analysis, chest and abdomen and pelvic or death) and OS (defined as the time from diagnosis to the
computed tomographic scan, serology for HIV, hepatitis-B
virus and hepatitis-C virus. The age range of the cohort was last follow-up). Six variables (risk factors) were assessed in
23-84 years. The number of previous therapies (NPTs) was TTF and OS univariate and multivariate survival analysis:
also evaluated in this series. The first-line chemotherapy sex (male, female); age (≤ 65, >65); LDH (≤ 300, >300);
was R-CHOP (n = 35), R-DHAP (n = 2), and hyper-CVAD stage (I-II, III-IV); IPI: (≤ 2, >2); and NPT (≤ 2, >2).
(n = 8). Most cases (27/45) received less than two previous
chemotherapies; 20/45 cases had bone marrow involvement The results of the Cox regression were expressed using
documented by biopsy (stage IV). both the hazard ratios with its related confidence interval
and related P value.
Treatment
GDP-R regimen consisted of gemcitabine (1,000 mg/m ) Survival curves were calculated using the Kaplan-Meier
2
intravenous (IV) on the days 1 and 8; cisplatin (75 mg/m ) method and the log-rank test was used to evaluate the
2
IV on the day 1; rituximab 375 mg/m IV on the day 2; differences between curves. Univariate survival analysis
2
oral dexamethasone 40 mg on the days 1-4; this regimen was performed including each risk factor in a Cox
was given every 3 weeks for a total of four courses. The regression model. All variables significantly influencing
standard anti-emetic regimen including ondansetron and survival in the univariate analysis were analyzed together
dexamethasone was provided prior to chemotherapy. in a Cox regression model as multivariate analysis, with
Chemotherapy was delayed on day 8 until recovery for the aim of studying the independent contribution of each
a maximum of 3 weeks if the neutrophil count was < 0.5 risk factor in explaining survivorship. Furthermore, the
× 10 /L and/or the platelet count was < 50 × 10 /L or if proportional hazard is always verified by using of log(-
9
9
the patient showed grade 3/4 non-hematological toxicity log) curves. The results of the Cox regression were
(except for nausea, vomiting, and alopecia). The dose expressed by hazard ratios with its related confidence
of cisplatin was reduced by 50% in the event of grade interval and related P value calculated by Wald test.
2 neurological toxicity or grade 1 renal toxicity. In the Regression coefficients (B) were also calculated. Statistics
event of febrile neutropenia, grade 4 thrombocytopenia was applied to the overall population (n = 45) and to each
or more than grade 3 non-hematological toxicity (except of the two subsets that were obtained after all patients
alopecia), treatment with 75% of the dose was given. were divided according to whether the IPI value was ≤ 2
Patient’s disease was evaluated for response 1 month or > 2 and the number of chemotherapeutic regimens was
after the end of treatment, and then every 3 months ≤ 2 or > 2 (27 vs. 18 pts, respectively). The cut-off value
during the first 2 years and every 6 months for further for the number of previous chemotherapies and IPI was
3 years. International Workshop NHL response criteria determined by a preliminary investigation considering the
were used to assess the response to treatment. [10] The available data from the study.
toxicity was estimated and graded according to the
National Cancer Institute Common Toxicity Criteria Differences were considered significant at P < 0.05.
version 3.0 grading system. Side-effects were described
in the overall population and in each of 2 subsets that Analyses were performed using the SPSS 21 technology.

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Journal of Cancer Metastasis and Treatment ¦ Volume 2 ¦ Issue 2 ¦ February 29, 2016 ¦