Evaluation of the MD Anderson tumor score for diffuse large B-cell lymphoma in the rituximab era.

OBJECTIVES: Diffuse large B-cell lymphoma (DLBCL) is an aggressive heterogeneous lymphoma with standard treatment. However, 30%-40% of patients still fail, so we should know which patients are candidates for alternative therapies. IPI is the main prognostic score but, in the rituximab era, it cannot identify a very high-risk (HR) subset. The MD Anderson Cancer Center reported a score in the prerituximab era exclusively considering tumor-related variables: Tumor Score (TS). We aim to validate TS in the rituximab era and to analyze its current potential role. METHODS: From GELTAMO DLBCL registry, we selected those patients homogeneously treated with R-CHOP (n = 1327). RESULTS: Five-years PFS and OS were 62% and 74%. All variables retained an independent prognostic role in the revised TS (R-TS), identifying four different risk groups, with 5-years PFS of 86%, 71%, 50%, and very HR (28%). With a further categorization of three variables of the original TS (Ann Arbor Stage, LDH and B2M), we generated a new index that allowed an improvement in HR assessment. CONCLUSIONS: (a) All variables of the original TS retain an independent prognostic role, and R-TS remains predictive in the rituximab era; (b) R-TS and additional categorization of LDH, B2M, and AA stage (enhanced TS) increased the ability to identify HR subsets.

High ten-year remission rates following rituximab, fludarabine, mitoxantrone and dexamethasone (R-FND) with interferon maintenance in indolent lymphoma: Results of a randomized Study.

We report a single-centre, randomized study evaluating the efficacy and safety of concurrent fludarabine, mitoxantrone, dexamethasone (FND) and rituximab versus sequential FND followed by rituximab in 158 patients with advanced stage, previously untreated indolent lymphoma, enrolled between 1997 and 2002. Patients were randomized to 6-8 cycles of FND followed by 6 monthly doses of rituximab or 6 doses of rituximab given concurrently with FND. All patients who achieved at least a partial response received 12 months of interferon (IFN) maintenance. Median ages were 54 and 55 years. The two groups were comparable with the exception of a higher percentage of females (65% vs. 43%) and baseline anaemia (23% vs. 11%) in the FND followed by rituximab group. Complete response/unconfirmed complete response rates were 89% and 93%. The most frequent grade ≥ 3 toxicity was neutropenia (86% vs. 96%). Neutropenic fever occurred in 21% and 16%. Late toxicity included myelodysplastic syndrome (n = 3) and acute myeloid leukaemia (n = 5). With 12·5 years of follow-up, no significant differences based on treatment schedule were observed. 10-year overall survival estimates were 76% and 73%. 10-year progression-free survival estimates were 52% and 51%. FND with concurrent or sequential rituximab, and IFN maintenance in indolent lymphoma demonstrated high response rates and robust survival.

Long-term outcomes, secondary malignancies and stem cell collection following bendamustine in patients with previously treated non-Hodgkin lymphoma.

Despite the long history of bendamustine as treatment for indolent non-Hodgkin lymphoma, long-term efficacy and toxicity data are minimal. We reviewed long-term data from three clinical trials to characterize the toxicity and efficacy of patients receiving bendamustine. Data were available for 149 subjects at 21 sites. The median age was 60 years at the start of bendamustine (range 39-84), and patients had received a median of 3 prior therapies. The histologies included grades 1-2 follicular lymphoma (FL; n = 73), grade 3 FL (n = 23), small lymphocytic lymphoma (n = 20), marginal zone lymphoma (n = 15), mantle cell lymphoma (n = 9), transformed lymphomas (n = 5), lymphoplasmacytic lymphoma (n = 2) and not reported (n = 2). The median event-free survival was 14·1 months. Nine of 12 attempted stem cell collections were successful. With a median follow-up of 8·9 years, 23 patients developed 25 cancers, including 8 patients with myelodysplastic syndrome/acute myeloid leukaemia. These data provide important information regarding the long-term toxicity of bendamustine in previously treated patients. A small but meaningful number of patients achieved durable remissions following bendamustine. These rigorously collected, patient-level, long-term follow-up data provide reassurance that bendamustine or bendamustine plus rituximab is associated with efficacy and safety for patients with relapsed or refractory indolent non-Hodgkin lymphoma.

Rituximab plus hyper-CVAD alternating with MTX/Ara-C in patients with newly diagnosed mantle cell lymphoma: 15-year follow-up of a phase II study from the MD Anderson Cancer Center.

Intensive chemotherapy regimens containing cytarabine have substantially improved remission durability and overall survival in younger adults with mantle cell lymphoma (MCL). However, there have been no long-term follow-up results for patients treated with these regimens. We present long-term survival outcomes from a pivotal phase II trial of rituximab, hyper-fractionated cyclophosphamide, vincristine, doxorubicin and dexamethasone alternating with methotrexate and cytarabine (R-HCVAD/MA). At 15 years of follow-up (median: 13·4 years), the median failure-free survival (FFS) and overall survival (OS) for all patients was 4·8 years and 10·7 years, respectively. The FFS seems to have plateaued after 10 years, with an estimated 15-year FFS of 30% in younger patients (≤65 years). Patients who achieved complete response (CR) after 2 cycles had a favourable median FFS of 8·8 years. Six patients developed myelodysplastic syndrome/acute myeloid leukaemia (MDS/AML) whilst in first CR. The 10-year cumulative incidence of MDS/AML of patients in first remission was 6·2% (95% confidence interval: 2·5-12·2%). In patients with newly diagnosed MCL, R-HCVAD/MA showed sustained efficacy, with a median OS exceeding 10 years in all patients and freedom from disease recurrence of nearly 15 years in almost one-third of the younger patients (≤65 years).

Prognostic significance of baseline peripheral absolute neutrophil, monocyte and serum ß2-microglobulin level in patients with diffuse large b-cell lymphoma: a new prognostic model.

There are limited reports that baseline peripheral absolute neutrophil count (ANC), absolute monocyte count (AMC), absolute lymphocyte count (ALC) and serum ß2-microglobulin level independently predict survival in patients with diffuse large B-cell lymphoma (DLBCL). To confirm these findings, we analysed these parameters together with components of the International Prognostic Index (IPI) in patients with newly-diagnosed DLBCL. We evaluated baseline clinical features for their ability to predict survival in 817 newly diagnosed, previously untreated patients with DLBCL who received frontline treatments between October 2001 and December 2011. The median age at diagnosis was 58 years. Multivariate analysis identified elevated baseline ANC (P = 0·036), AMC (P = 0·028) and serum ß2-microglobulin level (P < 0·001), poor performance status (P < 0·001) and high number of extranodal disease sites (P = 0·0497) as independent unfavourable predictors of OS; serum ß2-microglobulin level was the strongest predictor of survival outcomes among all the parameters. High baseline serum ß2-microglobulin, ANC and AMC levels are independent prognostic factors for short overall survival in patients with newly diagnosed DLBCL. Our new model, based on the above five parameters, better stratifies patients into various risk categories than the IPI for newly diagnosed DLBCL.

POEMS Syndrome: A Rare Disease With A Challenging Diagnosis.

A complex conglomerate of symptoms, signs, and abnormalities are present with POEMS syndrome, making the diagnosis, management and follow-up a challenge. Recognizing the disease early on may be difficult. Many patients are initially misdiagnosed as having others disorders, for example: multiple myeloma. There is no standard treatment for patients diagnosed with POEMS syndrome.

Metastatic Ovarian Tumor Masquerading as Atypical Pneumonia.

Krukenberg tumor is a malignancy in the ovary from a primary lesion in the gastrointestinal tract and a metastatic signet ring cell adenocarcinoma to the ovary. Stomach is the most common primary site, but other organs can serve as a primary site. The lymphatic system is the most likely route for metastasis. CA 125 levels can be used for screening for early detection of ovarian metastasis as well as for monitoring the course of disease. The prognosis of Krukenberg tumor is poor and no curative treatment is currently available.

Phase II study of bortezomib in combination with rituximab, cyclophosphamide and prednisone with or without doxorubicin followed by rituximab maintenance in patients with relapsed or refractory follicular lymphoma.

This non-comparative phase II study (ClinicalTrials.gov: NCT00715208) evaluated bortezomib in place of vincristine in established rituximab-chemotherapy regimens in relapsed/refractory follicular (FL) or marginal zone lymphoma (MZL). Patients were allocated (physician/patient preference) to receive six 21-d cycles of: bortezomib 1·6 mg/m(2) (days 1, 8), rituximab 375 mg/m(2) (day 1), cyclophosphamide 1000 mg/m(2) (day 1) and prednisone 100 mg (days 1-5; VR-CP; 47 FL, 1 MZL patients); or bortezomib, rituximab, prednisone per VR-CP, cyclophosphamide 750 mg/m(2) and doxorubicin 50 mg/m(2) (day 1; VR-CAP; 4 FL, 2 MZL, 1 chronic lymphocytic leukaemia patients). With VR-CP, the response rate was 77%, with a 27% complete response rate. After a median follow-up of 10·9 months, 40% of patients had relapsed/progressed or died. Median duration of response and progression-free survival was 21·9 and 14·9 months, respectively. Common drug-related grade ≥3 adverse events were neutropenia (25%), thrombocytopenia (6%) and lymphopenia (6%). Thirteen (27%) patients reported peripheral neuropathy (one grade 3). With VR-CAP, one FL patient achieved complete response and three FL and two MZL patients achieved partial responses. Three patients reported drug-related grade 1/2 peripheral neuropathy. Weekly bortezomib and rituximab represents an active, feasible treatment platform in FL. VR-CP was active and well tolerated in patients with relapsed/refractory FL.

Clinical and pathological features of colorectal cancer in patients at a community hospital in Puerto Rico.

OBJECTIVE: Colorectal cancer (CRC) is among the most common cancers in Puerto Rico. Few studies have correlated clinical and pathological variables with the overall survival of CRC patients in Puerto Rico. We report the clinical and pathological characteristics of patients who underwent surgical resection at a community hospital in Puerto Rico. METHODS: Demographic and pathological variables of patients who underwent CRC surgery at Hospital del Maestro from 2006 through 2011 were reviewed. Descriptive statistics (mean, range, and frequency) and the Cox proportional hazards model were used to determine the influence of demographic and pathological variables on survival, after adjusting for age. RESULTS: Two hundred and five CRC pathology reports were reviewed. Adenocarcinoma represented the most common pathology (202/205; 98.5%). Females represented 52% of the population (106/202) while males represented 48% (96/202). The median age was 71 years (30-96). The right colon was the most common site of presentation (49.7%; 100/201). Stage III was the most common stage at presentation. The presence of mucin, perineural or lymphatic invasion and tumor size were not related to decreased survival. Being male, having a higher stage at diagnosis, and having a moderately or poorly differentiated tumor were characteristics related to decreased survival. CONCLUSION: This study provides information on clinical and pathological variables and their influence on the overall survival of CRC patients at a community hospital in Puerto Rico. Further research must be performed to identify potential disparities and their influence on the prognosis of this patients.

Clinical Features and Therapeutic Outcomes Comparing Primary Mediastinal Large B-cell Lymphoma to Mediastinal Hodgkin Disease.

Currently, there is limited data available comparing Primary Mediastinal Large B-cell Lymphoma (PMBL) and mediastinal Hodgkin disease, nodular sclerosis type (HDNS). This is a retrospective cohort study that compares the clinical features, histology through immunohistochemistry (IHC) and treatment outcomes of 19 cases of PMBL and 39 cases of HDNS diagnosed over 13 years at a single institution in San Juan, PR. Superior Vena Cava syndrome (SVCS) and elevated Lactate Dehydrogenase (LDH) levels were more frequently seen in the PMBL cohort. At the median follow-up visit, of 74 months, no significant difference was seen in overall survival or progression free survival between PMBL and HDNS. Almost all of the relapses in the PMBL group occurred within 12 months of diagnosis. Our data suggests that PMBL and HDNS differ in their clinical presentation and have a favorable prognosis.

Long term results of a phase 2 study of vincristine sulfate liposome injection (Marqibo(®) ) substituted for non-liposomal vincristine in cyclophosphamide, doxorubicin, vincristine, prednisone with or without rituximab for patients with untreated aggressive non-Hodgkin lymphomas.

Vincristine sulfate liposome injection (VSLI; Marqibo(®) ; M) is active in relapsed and refractory lymphomas, and approved in the United States for relapsed and refractory adult acute lymphocytic leukaemia. We evaluated VSLI (2·0 mg/m(2) without dose cap) substituted for non-liposomal vincristine (VCR) in a cyclophosphamide, doxorubicin, vincristine, prednisone ± ritiximab (CHOP±R) regimen, creating CHMP±R in 72 untreated, aggressive non-Hodgkin lymphoma patients, including 60 with diffuse large B-cell lymphoma (DLBCL). The overall response rate was 96% (69/72) including complete response (CR) in 65 (90%) and unconfirmed CR in 2 (3%). Median progression-free survival (PFS) and overall survival (OS) were not reached at median follow-up of 8 and 10·2 years, respectively. The 5- and 10-year PFS and OS were 75%, 63%, 87%, and 77%, respectively. Despite VSLI exposure of up to 35 mg, the safety profile of CHMP±R was comparable to that reported for CHOP±R. Grade 3 peripheral neuropathy was reported in 2 (3%) patients; there was no reported Grade 3/4 constipation. CHMP±R was highly active, generally well tolerated, and compared favourably to historical trials with R-CHOP in DLBCL. This enhanced activity probably reflects VCR dose intensification, pharmacokinetic optimization, and enhanced delivery afforded by VSLI. A Phase 3 trial of R-CHMP versus R-CHOP in elderly patients with untreated DLBCL is ongoing.

Recent advances in the management of mantle cell lymphoma.

PURPOSE OF REVIEW: This review will discuss the most recent literature regarding frontline therapy, treatment of patients not eligible for intensive chemotherapy, and novel agents for relapsed/refractory patients with mantle cell lymphoma (MCL). RECENT FINDINGS: Longer follow-up of previously studied intensive regimens still demonstrates encouraging results, but late relapses are still evident. Consolidation and maintenance strategies continue to be attractive options to be explored in this disease that is characterized by frequent relapses and short remissions. The combination of bendamustine-rituximab was demonstrated to be noninferior and less toxic to R-CHOP and should be considered the new standard of care for elderly patients. Multiple novel agents directed towards different molecular targets like BTK, mTOR, PI3K, HDAC, and BCL-2, involved in the pathogenesis of MCL have shown promising results. SUMMARY: Management of MCL still represents a challenge due to heterogeneity of the disease. As we approach the molecular era of oncology, future strategies should focus on combination of newer agents with known effective regimens to improve outcome.

Lenalidomide in combination with rituximab for patients with relapsed or refractory mantle-cell lymphoma: a phase 1/2 clinical trial.

BACKGROUND: The combination of rituximab and lenalidomide has shown promise for the treatment of mantle-cell lymphoma (MCL) in preclinical studies. We aimed to identify the maximum tolerated dose (MTD) of lenalidomide when combined with rituximab in a phase 1 trial and to assess the efficacy and safety of this combination in a phase 2 trial in patients with relapsed or refractory MCL. METHODS: Patients with relapsed or refractory MCL who had received one to four previous lines of treatment were enrolled in this single-arm, open-label, phase 1/2 trial at MD Anderson Cancer Center. In phase 1, to identify the MTD of lenalidomide, four patient cohorts received escalating doses (10, 15, 20, and 25 mg) of daily oral lenalidomide on days 1-21 of each 28-day cycle. 375 mg/m(2) intravenous rituximab was also administered in four weekly doses during cycle 1 only. In phase 2, patients received rituximab plus the MTD of lenalidomide, following the same cycles as for phase 1. Treatment in both phases continued until disease progression, stem-cell transplantation, or severe toxicity. The primary efficacy endpoint was overall response (complete or partial response). The secondary efficacy endpoint was survival. We used the Kaplan-Meier method to estimate response duration, progression-free survival, and overall survival. Analysis was by intention to treat. This study is registered with ClinicalTrials.gov, number NCT00294632. FINDINGS: 52 patients were enrolled between Feb 10, 2006 and July 30, 2009, 14 in phase 1 and 44 (including six patients who received the MTD of lenalidomide in the phase 1 portion) in phase 2. The MTD was 20 mg lenalidomide. One patient who was treated with 25 mg lenalidomide developed a grade 4 non-neutropenic infection and died. In the phase 2 portion of the study, grade 3-4 haematological toxicities included neutropenia (29 patients), lymphopenia (16 patients), leucopenia (13 patients), and thrombocytopenia (ten patients). There were only two episodes of febrile neutropenia. Among 44 patients in phase 2, 25 (57%) had an overall response: 16 (36%) had a complete response and nine (20%) had a partial response. The median response duration was 18·9 months (95% CI 17·0 months to not reached [NR]). The median progression-free survival was 11·1 months (95% CI 8·3 to 24·9 months), and the median overall survival was 24·3 months (19·8 months to NR). Five of 14 patients who had received bortezomib treatment before enrolment achieved an overall response. INTERPRETATION: Oral lenalidomide plus rituximab is well tolerated and effective for patients with relapsed or refractory MCL. FUNDING: Celgene.

An Unexpected Presentation of a Maxillary Non-Hodgkin Lymphoma in an Elderly Hispanic Patient.

Extranodal NK/T-cell lymphoma (ENKTL), nasal type and aggressive NK cell leukemia are rare in Western World been less than 1% in USA to 8% in Asia among Non-Hodgkin's lymphomas. It is aggressive, with poor outcome and optimal treatment is unclear. A combination therapy that includes Peg-Asparaginase (SMILE) has been employed in young patients. An 85-year-old Puerto Rican male presented with anorexia, epistaxis, vertigo and involuntary facial movements. He was treated with injectable Onabotulinum toxin A due to suspicion of a hemifacial spasm. However, a CT scan demonstrated a left maxillary sinus lesion extending into the left middle turbinate with biopsy consistent with ENKTL. We adjusted therapy to patient's age and performance receiving Gemcitabine-Oxaliplatin (Gemox) with radiation obtaining a complete response with persistent negative Epstein Barr DNA titers. ENKTL is a rare disease initially misdiagnosed in our elderly patient, who demonstrated adequate response with a modified therapeutic regime.

Rectal adenocarcinoma: proposal for a model based on pretreatment prognostic factors.

OBJECTIVE: Currently the choice of chemotherapy regimen in rectal cancer is made prior to surgery in contrast to colon cancer where it is made postoperatively after the pathological stage has been determined. If we could identify which are the important pretreatment prognostic factors in rectal cancer, we could then target those patients with unfavorable features to investigate potentially more effective preoperative chemotherapy regimens aimed at those with unfavorable features. The present study aimed to determine pre-treatment prognostic factors that are associated with an unfavorable outcome. METHODS: A retrospective review of 99 rectal cancer patients operated at the Auxilio Mutuo Hospital, San Juan, Puerto Rico, and the San Pablo Hospital, Bayamón, Puerto Rico was done. Socio-demographic, clinical and treatment data were collected. RESULTS: Of the 99 cases, 54% were males. The mean age +/- standard deviation was 62.2 +/- 10.4. In age-adjusted Cox model, male gender (HR [95%CI]: 3.32 [1.09-10.13]), mucinous carcinoma (HR [95% CI]: 3.67 [1.25-10.77]), and clinical stages II & III (HR [95%CI]: 8.19 [1.08-62.08]) were predictors of poor prognosis. In the multivariate age-adjusted analysis, a tendency towards a poorer prognosis was observed for male patients (HR: 2.60), carcinoembryonic antigen level > or =5 ng/ml (HR: 2.55), mucinous carcinoma (HR: 2.96), and clinical stages II & III (HR: 4.96), although results were not statistically significant (p > 0.05). CONCLUSION: Although current therapeutic results are relatively favorable with preoperative 5-fluorouracil and radiotherapy, future clinical trials should address the management of those cases with adverse pretreatment prognostic factors so that they can be treated with potentially more effective albeit more toxic chemotherapy regimens.

Triple negative breast cancer: a retrospective study of Hispanics residing in Puerto Rico.

OBJECTIVE: Triple-negative breast cancer (TNBC) demonstrates unique clinicopathological characteristics and survival outcomes. Several studies have documented important disparities in Hispanic women compared to other racial/ethnic groups; nevertheless, data on this entity in a population based Latin country are very limited. Our goal was to assess demographic and clinicopathological characteristics in essentially a pure population of Puerto Rican females with TNBC residing in Puerto Rico, as well as to determine their overall survival and progression-free survival in order to compare with published data. METHODS: By searching the electronic medical records data base, 54 patients were identified as TNBC. The median follow-up period was 25 months (range, 2-78). Univariate analysis of pretreatment risk factors was conducted. RESULTS: The median age at diagnosis was 55 years. Of 54 cases, 51 had stage I-III presentation. T1/T2 tumors were found in 88.9% and absence of nodal involvement in 68.5%. Prognostic factors for progression free survival (PFS) that were statistically significant were lymph node involvement (p = 0.02), tumor size > 2 cm (p = 0.037) and stage IV (p = 0.00002). The 5-year overall survival and PFS were 81% and 80%, respectively. CONCLUSION: RESULTS are very similar to published data on females from North America and Europe. Differences in clinical outcome and stage at diagnosis in Hispanic women with TNBC are more likely explained by socioeconomic status and adequate access to care, rather than biological/genetic differences. The association of triple-negative breast cancer with poor prognosis deserves re-evaluation given that patients with negative node involvement and no metastasis appear to be highly

Home-based management of COVID-19 by identification of low-risk features.

BACKGROUND: Covid-19 is a triphasic disorder characterized by a viral phase lasting 7-10 days from first onset of symptoms. In approximately 20% it is followed by a second stage heralded by elevation of pro-inflammatory markers such as ferritin, IL-6, CRP, LDH and D-dimers. We hypothesized that those with few abnormalities would have a low risk for progression to respiratory insufficiency and could be monitored at home without treatment. METHODS: Inclusion criteria included age >21, O2 saturation >90%. To be observed without treatment patients could not have >1 of the following: CRP > 10 mg/dL, high LDH, ferritin > 500 ng/ml, D-dimer > 1 mg/L, IL-6 > 10 pg/ml, absolute lymphocyte count <1,000, O2 sat <94%, or CT chest evidence of pneumonia. Primary endpoint: progression to respiratory failure. Secondary endpoint: 28-day survival. RESULTS: Of 208 entered, 132 were monitored without therapy. None progressed to respiratory failure or died. CONCLUSIONS: We have shown that our approach can identify cases who can safely be observed without treatment, thus avoiding expensive, potentially toxic therapies, and circumventing unnecessary, costly hospitalizations. These results support our hypothesis that after applying our criteria, 64% of Covid-19 cases can be monitored as outpatients without therapy.

Single-Arm, Open-Label Phase 2 Trial of Preemptive Methylprednisolone to Avert Progression to Respiratory Failure in High-Risk Patients with COVID-19.

Introduction: Covid-19 is a triphasic disorder first typified by a viral phase that lasts from the first onset of symptoms until seven days later. This is followed by a second and third phase, initially characterized by the appearance of lung infiltrates, followed in 20% by respiratory failure. The second phase is usually heralded by an elevation of serologic inflammatory markers including CRP, ferritin, IL-6, LDH as well as D-dimers. Approximately 20% proceed to the second phase and are usually then treated with dexamethasone, provided they are oxygen-dependent since these are the only cases that benefit from dexamethasone. If we had objective criteria to predict this 20% that develop severe illness, they could preemptively be treated with steroids. In this exploratory study we investigated the early use of preemptive steroids in the setting of early disease, in high-risk non-oxygen dependent cases. Methods: Eligible patients were those 21 years or older with a diagnosis of Covid-19 and oxygen saturation ≥91%. For patients to be classified as high-risk, they had to exhibit two or more of the following abnormalities 7-10 days after first symptom: IL-6 ≥ 10 pg/ml, ferritin > 500 ng/ml, D-dimer > 1 mg/L (1,000 ng/ml), CRP > 10 mg/dL (100 mg/L), LDH above normal range lymphopenia (absolute lymphocyte count <1,000 /µL), oxygen saturation between 91-94%, or CT chest with evidence of ground glass infiltrates. Primary endpoint was progression to respiratory failure. CALL score method was used to predict the expected number of cases of respiratory failure. High risk patients received methylprednisolone (MPS) 80 mg IV daily x 5 days starting no earlier than seven days from first onset of symptoms. The primary endpoint was progression to hypoxemic respiratory failure defined as PaO2 <60 mm Hg or oxygen saturation ≤90%. Secondary endpoints included survival at 28 days from registration, admission to intensive care and live discharge from the hospital. Change in levels of inflammatory markers and length of hospitalization were also assessed. Results: In 76 patients, the expected number with respiratory failure was 30 (39.5%), yet only 4 (5.3%) developed that complication (p=.00001). Survival at 28 days was 98.6%.Improvement in inflammatory markers correlated with favorable outcome. Conclusions: Our results are encouraging and suggest that this approach is both effective and safe.

Ten-year follow-up after intense chemoimmunotherapy with Rituximab-HyperCVAD alternating with Rituximab-high dose methotrexate/cytarabine (R-MA) and without stem cell transplantation in patients with untreated aggressive mantle cell lymphoma.

Mantle cell lymphoma (MCL) has a poor overall survival after treatment with conventional chemotherapy. Intense chemoimmunotherapy without consolidation stem cell transplantation is a potential therapeutic option. We report on a prospective Phase II study with rituximab in combination with fractionated cyclophosphamide, vincristine, doxorubicin and dexamethasone (R-Hyper-CVAD) alternating with rituximab in combination with high-dose methotrexate-cytarabine (R-MA) in untreated patients with diffuse and nodular MCL and their blastoid variants. Ninety-seven patients were treated, of whom 97% responded and 87% achieved a complete remission. At 10 years of follow up (median 8 years), the median overall survival (OS) for all patients had not been reached and the median time to failure (TTF) for all patients was 4.6 years, without a plateau in the curves. For the group of patients aged 65 years or younger, the median OS had not been reached and the median TTF was 5.9 years. Multivariate analysis revealed pre-treatment serum levels of beta(2) microglobulin, International Prognostic Index (IPI) score and mantle cell IPI (MIPI) score, as predictive of both OS and TTF. We conclude that intense chemoimmunotherapy without stem cell transplantation is effective for untreated aggressive MCL.