Rosai-Dorfman disease (RDD) is a rare disorder composed of a proliferation of histiocytes with varied clinical manifestations.
In this retrospective observational study, we obtained demographic, ...clinical, and outcome data from the medical records of 10 adult patients with RDD seen in the Department of Lymphoma and Myeloma at MD Anderson Cancer Center between 1995 and 2015.
Patients had a median age of 56 years (range, 20-81 years) with equal gender distribution. Five patients were initially treated with systemic therapy. Five received cladribine as initial therapy or for relapse. Other therapeutic agents included clofarabine, lenalidomide, and steroids. The overall response rate was 80% in patients receiving cladribine, with a median progression-free survival of 29 months. Surgery, radiotherapy, and observation were also treatment options for localized disease. With a median follow-up of 65 months, none of the patients have died.
Currently, there is no standard of care for RDD. Treatment should be personalized for each patient depending on the clinical presentation, course of the disease, and prior treatment history. Purine analogues provide excellent responses; however, surgical resection and observation are also suitable for specific cases.
Rosai-Dorfman disease is a rare disorder composed of a proliferation of histiocytes. Owing to the small number of cases and the variable clinical course, the optimal clinical management of this disease is challenging. We present our experience with management of this rare disease.
Summary
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.
Micro-Abstract An index based on the initial absolute lymphocyte and monocyte counts may provide prognostic information regarding outcome beyond that of the International Prognostic Factors Index in ...management of patients with untreated diffuse large cell lymphoma who are receiving R-CHOP chemotherapy.
Summary
This phase II study evaluated the safety and efficacy of denileukin diftitox, an interleukin‐2–diphtheria toxin fusion protein, in relapsed/refractory T‐cell non‐Hodgkin lymphoma (T‐NHL), ...excluding cutaneous T‐cell lymphoma. Eligible patients received denileukin diftitox 18 μg/kg/d × 5 d every 3 weeks for up to eight cycles. Tumour staging was performed every two cycles and the primary endpoint was the objective response rate complete response (CR) + partial response (PR). For 27 patients enrolled, median age: 55 years (range 26–80 years), 70·4% male, and mean prior therapies: 2·5 (range 1–6). Objective responses (six CRs, seven PRs) were achieved in 13 patients (48·1%), stable disease in eight (29·6%) and six (22·2%) had progressive disease. An objective response was achieved in eight of 13 patients (61·5%) with CD25+ tumours (four CR/four PR) and five of 11 patients (45·5%) with CD25− tumours (two CR/three PR). Median progression‐free survival was 6 months (range, 1–38+ months). Most adverse reactions were grade 1/2 and transient. No grade 4–5 toxicities were reported. Denileukin diftitox had significant activity and was well tolerated in relapsed/refractory T‐NHL, with responses observed in both CD25+ and CD25− tumours. Further studies of denileukin diftitox in combination with other agents are warranted in previously untreated and relapsed/refractory T‐NHL.
In 2 randomized phase 3 trials BR resulted in longer progression-free survival (PFS) than frontline R-CHOP in patients with indolent and mantle cell lymphoma. However, in subset analyses of ...follicular lymphoma (FL), the results were incongruent. We conducted a retrospective matched-pair analysis to compare the outcome of patients with advanced stage FL, receiving frontline BR (N = 73) or R-CHOP (N = 73), matched by age, gender, stage, and FL International Prognostic Index score. On multivariable analysis, baseline maximum standardized uptake value (SUV
max
) >13 was associated with use of R-CHOP (p = .001). After a median follow-up of 69 months for the BR arm and 126 months for the R-CHOP arm, 5-year PFS was 80% and 70%, respectively (p = .07). After adjusting for SUV
max
>13, the trend for better PFS in BR was not maintained. Prospective studies are needed to validate the role of pretreatment SUV
max
as a stratification factor in future randomized therapeutic trials in FL.
Hodgkin transformation is a rare complication of chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL). In this study, the authors assessed the incidence, presenting characteristics, and ...outcomes of patients with CLL/SLL who developed Hodgkin lymphoma (HL).
An electronic database search of patients with CLL/SLL who presented at The University of Texas M. D. Anderson Cancer Center Department of Leukemia between 1975 and 2005 was performed.
Among 4121 patients with CLL/SLL, 18 patients (0.4%) developed HL. Presenting features included B-symptoms (67%), lymph node enlargement (79%), splenomegaly (43%), hepatomegaly (29%), hypercalcemia (6%), infection (6%), and mental status changes (6%). The median age was 72 years (range, 49-81 years), and there was a male preponderance (78%). The median time from CLL to HL diagnosis was 4.6 years (range, 0-12.9 years). Fourteen patients (78%) had been previously treated for CLL/SLL. Ten patients (56%) had received >1 prior therapy. The median beta2-microglobulin level was 4.5 mg/L, and the median lactate dehydrogenase level was 610 IU/L. Epstein-Barr virus (EBV) was positive by in situ hybridization for EBV-encoded RNA in 3 of 4 tested patients. Fourteen patients (78%) received chemotherapy. The overall response rate was 44% (complete response rate, 19%). The median overall survival duration was 0.8 years (range, 0.03 years-6.7+ years). The median failure-free survival (FFS) duration was 0.4 years.
The rates of response, survival, and FFS in patients with Hodgkin transformation of CLL/SLL were inferior to those reported in patients with de novo HL and were similar to those in patients with Richter syndrome.
Background
Relapsed or refractory mantle cell lymphoma (MCL) has a poor prognosis. The best outcome is achieved in patients who have a partial or complete response to salvage treatment and proceed to ...allogeneic stem cell transplant.
Patients and Methods
Twenty‐one patients were given a combination regimen of bortezomib, cyclophosphamide, and rituximab at MD Anderson Cancer Center as part of a single‐arm, prospective, open‐label phase II clinical trial. The median age was 66 years, with a median number of prior treatments of three. Sixty‐seven percent had failed intensive chemoimmunotherapy and 43% were intermediate/high risk according to the MCL international prognostic index score, with a median Ki‐67 proliferation index of 45% in those who were tested.
Results
The rates of overall and complete response achieved were 74% and 42%, respectively, with median progression‐free and overall survivals of 9 months and 36.4 months, respectively. The regimen's toxicity profile was acceptable; only 25% of the cycles resulted in grade 3 or 4 neutropenia or thrombocytopenia, and only 3% of cycles produced grade 3–4 fatigue. There were no episodes of grade 3–4 neuropathy.
Conclusion
The combination of bortezomib with cyclophosphamide and rituximab is an effective and well‐tolerated regimen in patients with relapsed/refractory MCL. Because of its low toxicity, future combinations of this regimen with other promising drugs that have different mechanisms of action offer a realistic possibility that may improve outcomes for patients who have MCL.
Implications for Practice
The combination of bortezomib with cyclophosphamide and rituximab represents an additional effective novel salvage regimen for mantle cell lymphoma. This combination adds to the growing list of treatment options available for patients with mantle cell lymphoma.
Relapsed or refractory mantle cell lymphoma has a poor prognosis. This article presents the result of a phase II trial of the combination regimen of rituximab, bortezomib, and cyclophosphamide in patients with relapsed or refractory aggressive mantle cell lymphoma.
Summary
We conducted a prospective randomized phase II study to evaluate two chemotherapy regimens: (i) rituximab plus hyperfractionated cyclophosphamide, vincristine, doxorubicin and dexamethasone ...(R‐HCVAD) alternating with rituximab, high‐dose methotrexate, and cytarabine (R‐MA) and (ii) rituximab, cyclophosphamide, doxorubicin, vincristine and prednisone (R‐CHOP) in diffuse large B‐cell lymphoma (DLBCL). This study randomized patients aged ≤60 years with DLBCL and an age‐adjusted international prognostic index ≥2 to R‐HCVAD/R‐MA or R‐CHOP based on a Bayesian adaptive algorithm. Interim analysis of the first 26 eligible patients showed that the complete response rate (CRR) was higher with R‐HCVAD/R‐MA than R‐CHOP (P = 0·03); thus, R‐CHOP arm was closed. In the final analysis, 49 and 10 eligible patients were treated in R‐HCVAD/R‐MA and R‐CHOP arms respectively; CRR were 82% and 60% respectively (P = 0·13); 3‐year progression‐free survival (PFS) rates were 75·7% and 77·8% respectively (P = 0·53). In the R‐HCVAD/R‐MA arm, 3‐year PFS rates in patients aged 46–60 years and ≤45 years were 70·3% and 87·1% respectively (P = 0·13), and the treatment‐associated early mortality rate in patients >45 years was 12%. In conclusion, R‐HCVAD/R‐MA is associated with excellent outcome in patients ≤45 years old. However, in patients >45 years old, R‐HCVAD/R‐MA is associated with unacceptable mortality rates.
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