High-dose methylprednisolone can induce remissions in patients with fludarabine-refractory chronic lymphocytic leukaemia

2010 ◽  
Vol 46 (12) ◽  
pp. 2145-2149 ◽  
Author(s):  
Wei Xu ◽  
Kou-Rong Miao ◽  
Ming Hong ◽  
Dan-Xia Zhu ◽  
Cheng Fang ◽  
...  
Keyword(s):  
Chronic Lymphocytic Leukaemia ◽  
Lymphocytic Leukaemia ◽  
High Dose ◽  
High Dose Methylprednisolone

High Dose Methylprednisolone and Rituximab Is an Effective Therapy in Advanced Refractory Chronic Lymphocytic Leukaemia Resistant to Fludarabine Therapy.

Blood ◽  
2007 ◽  
Vol 110 (11) ◽  
pp. 3125-3125
Author(s):  
Moez Dungarwalla ◽  
Pamala Kanagasabapathy ◽  
Samar Kulkarni ◽  
Steve O. Evans ◽  
Unell Riley ◽  
...  
Keyword(s):  
Chronic Lymphocytic Leukaemia ◽  
Viral Infections ◽  
Lymphocytic Leukaemia ◽  
Fungal Infections ◽  
Single Agent ◽  
Progression Free Survival ◽  
High Dose ◽  
Fish Analysis ◽  
Free Survival ◽  
High Dose Methylprednisolone

Abstract The management of refractory advanced chronic lymphocytic leukaemia (CLL) continues to pose a considerable challenge to the clinician. CLL patients who are refractory or become resistant to fludarabine containing regimens currently have a poor prognosis. High dose methylprednisolone (HDMP) has been shown to be an effective therapeutic option in patients who are resistant to fludarabine particularly those with bulky lymphadenopathy or refractory cytopenias who are unsuitable for alemtuzumab therapy. We have used HDMP in combination with the anti-CD20 monoclonal antibody, Rituximab, to treat 14 patients with advanced refractory CLL. Eight of fourteen patients were male. The median age was 62.5 years (range 30–71). Twelve patients had bulky lymphadenopathy with nodal masses greater than 5 centimetres in diameter. Nine patients had Binet stage C and the remainder were stage B. Autoimmune manifestations were present in five of the patients, and in one of them fludarabine therapy was contraindicated due to active autoimmune haemolysis. FISH analysis was performed to detect 17p, 11q and 13q deletions and showed 11q23 deletions in five patients. The overall response rate was 93% with a median progression free survival (PFS) of seven months. Two patients achieved a CR, another a nodular PR and 10 patients had a PR. Responses were seen in all 4 patients who had not responded to alemtuzumab as a single agent. Only one patient failed to respond. The median survival was 20 months. All five patients with 11q23 deletions responded, and the mean progression free survival in this subgroup was 10.5 months. These results compare extremely favourably with our own previous study (Thornton et al, 1998) that used HDMP alone in the management of advanced/refractory CLL where only 43% of patients responded and no patients achieved a CR. We have demonstrated that the combination of HDMP with rituximab is more effective than HDMP alone (p<0.01) in advanced refractory CLL. Although HDMP in combination with rituximab causes little or no myelosuppression, 6/14 patients (43%) developed opportunistic fungal or viral infections and this included fungal mould infections, fungal yeast infections and opportunistic viral infections. Three patients died of pulmonary fungal infections, although 2 of these patients had been retreated with alternative regimens. While the immunosuppressive effects of high dose steroids are well recognised, it appears that the addition of rituximab has made these patients more prone to opportunistic infections. In summary, HDMP in combination with rituximab is an effective rescue regime in purine analogue refractory CLL particularly in patients with bulky lymphadenopathy who are unsuitable for alemtuzumab, and in patients with 11q23 deletions.

Rituximab in Combination with High-Dose Steroids in Advanced, Refractory Chronic Lymphocytic Leukaemia.

Blood ◽  
2007 ◽  
Vol 110 (11) ◽  
pp. 4719-4719
Author(s):  
John Quinn ◽  
Sajir Mohamedbhai ◽  
Marilyn Treacey ◽  
Shirley D’Sa ◽  
Amit Nathwani
Keyword(s):  
Stem Cell ◽  
Chronic Lymphocytic Leukaemia ◽  
Stem Cell Transplant ◽  
Lymphocytic Leukaemia ◽  
Median Number ◽  
High Dose ◽  
Cell Transplant ◽  
Allogeneic Stem Cell Transplant ◽  
Post Transplant ◽  
Reduced Intensity

Abstract High-dose methlyprednislone (HDMP) is active in refractory chronic lymphocytic leukaemia (CLL), and rituximab, although showing limited efficacy as a single agent, is effective when used in combination with other cytotoxic agents. Early relapse (<12 months) after purine-analogue based treatment poses a difficult management problem as older patients may be unable to tolerate treatment intensification. This retrospective audit examines the outcome in patients with advanced, refractory/relapsed CLL treated with a combination of high-dose steroids and rituximab. Eleven patients with CLL were treated with rituximab (375mg/m2) and high-dose steroids between 2003 and 2007. Ten patients had advanced and/or refractory disease and one patient had severe autoimmune haemolytic anaemia complicating early-stage CLL. Median age was 70 (range 54–82) and there were 7 male and 4 female patients. Nine patients had Binet stage C disease. Six of the 7 patients for whom results were available had germ-line variable heavy chain immunoglobuliun genes. Median number of prior treatments was 2 (range 1–6) with 9 patients having already received a fludarabine based-regimen. Six patients received a combination of rituximab and high-dose methylprednisolone (1gm/m2 on days 1–5) and 5 patients received a combination of rituximab and high-dose dexamethasone (40mg daily on days 1–4) and. Cycles were repeated every 28 days and the median number of cycles received was 4 (3–6). Antiviral and anti-PCP prophlaxis with aciclovir and co-trimoxazole was routinely prescribed. Response was assessed according to the NCI working group criteria. There was one complete response (CR) and 7 partial responses (PR). Furthermore, 2 of the patients who achieved a PR were successfully salvaged prior to reduced-intensity allogeneic stem-cell transplant and both remain in complete remission (CR) post-transplant. The other 3 patients had minor responses that did not meet NCI response criteria. Median duration of response was 13 months (6–35), excluding the 2 patients who received allogeneic transplants. Three patients required hospital admission with infective complications during treatment. No other significant toxicity was observed. 3 patients have died, none of whom had attained a PR. In conclusion, we found that rituximab in combination with high-dose steroids is a safe and well-tolerated combination in patients with advanced refractory CLL. One patient achieved a CR and we observed a PR in 7/11 patients. Importantly, 2 of these patients were successfully salvaged prior to reduced-intensity conditioning allogeneic stem-cell transplant and both remain in CR at 4 and 12 months respectively post-transplant.

The Use of Low-Dose Alemtuzumab as Single Agent in the Treatment of Complication in Advanced Chronic Lymphocytic Leukaemia

Blood ◽  
2008 ◽  
Vol 112 (11) ◽  
pp. 4212-4212
Author(s):  
Luca Laurenti ◽  
Michela Tarnani ◽  
Idanna Innocenti ◽  
Silvia De Matteis ◽  
Simona Sica ◽  
...  
Keyword(s):  
Chronic Lymphocytic Leukaemia ◽  
Peripheral Blood ◽  
Low Dose ◽  
Lymphocytic Leukaemia ◽  
Single Agent ◽  
Previous Treatment ◽  
High Dose ◽  
End Of Treatment ◽  
Hb Concentration ◽  
Cmv Reactivation

Abstract There are some report in literature about the use of Alemtuzumab in patients affected by advanced B-cell chronic lymphocytic leukaemia who developed severe transfusion-dependent autoimmune haemolytic anaemia (AIHA) resistant to conventional therapy or cutis involvement. We report the use of low-dose Alemtuzumab in 4 AIHA patients and in 1 case of eyelid leukaemia cutis. Alemtuzumab was given subcutaneously at 10 mg three times weekly for 30 administrations (10 weeks). Treatment was stopped for progression disease, grade IV thrombocytopenia and/or infections or Cytomegalovirus (CMV) reactivation. Prophylaxis consiste on co-trimoxazole and aciclovir from the start of the treatment until 2 months after the end of treatment. Peripheral blood count, biochemical screening, antigenemia and CMV DNA analysis, reticulocyte count were conducted weekly. DAT and IAT were studied every two weeks during the treatment. Patient with eyelid leukaemia cutis underwent to histological examination before and after the end of treatment. AIHA response, was defined as the independence from RBC transfusion and a concomitant &gt; 2.0 g/dl rise in Hb concentration. Four male patients developed DATpositive AIHA at a median of 44.5 months from the B-CLL diagnosis. Previous treatment for B-CLL, stage and haemoglobin (Hb) values at Alemtuzumab administration are shown in table 1. Three patients underwent to RBCu transfusion before Alemtuzumab treatment, and one also during the treatment (2RBCu). The median haemoglobin value at first Alemtuzumab administration was 8.25 gr/dl. (table1) Two patients showed CMV reactivation at 5th and 6th week of therapy and were treated with oral ganciclovir for 14 and 21 days respectively. AIHA response was reached at median of 7 weeks of Alemtuzumab therapy in all patients while the median duration time of response to Alemtuzumab therapy was 10 months. Two patients underwent to further treatment for DAT negative progressive disease after 9 and 10 months from the end of Alemtuzumab therapy respectively, one patients was treated after 26 months for AIHA relapse, while the last patients even if showed AIHA remission is currently at 6th week of Alemtuzumab treatment (Hb 8g/dl). At the end of Alemtuzumab administrations the median Hb concentration was 12.7 g/dl regarding clinical responses, the patient no.1 obtained SD, the other 2 PR. Patient with leukemia cutis (LC) showed a constant reduction of eyelid involvement until clinical resolution after 240 mg of Alemtuzumab. Now a day, a manteinance therapy is ongoing with Alemtuzumab 30 mg monthly maintaining complete remission of eyelid localization and partial remission of CLL 10 months after induction therapy. In All patients the therapy has been well tolerated, with mild haematological and extra-haematological side effects (grade I). No episode of febrile neutropenia or bacterial/fungal infection occurred during the treatment. Our data confirmed the literature data about the use of Alemtuzumab, even if with low-dose, as salvage treatment for transfusion-dependent and resistant AIHA in pre-treated B-CLL patients and show a new indication for LC involvement. Table 1: Patient’s clinical characteristics Age/Sex Binet/Rai Stage Months from B-CLL diagnosis and AIHA/LC Previous treatment for B-CLL (number of cycles) Biological Parameter Months between last B-CLL therapy-AIHA/LC Hb at baseline Alemtuzumab treatment (gr/dl) DAT/IAT 68/M C/IV 9 CHOP(6), CVP(3) Unmutated IgVH&#x2028; Zap-70 +&#x2028; CD38 +&#x2028; Del17p 1 9.4 DAT 4+&#x2028; (IgG 4+)&#x2028; IAT 4+ 53/M C/IV 31 Chl/Pdn(6), FC(6), Pdn(6), Ig, Splenectomy Mutated&#x2028; Zap-70 −&#x2028; Normal karyotipe 3 7.1 DAT 2+&#x2028; (IgG 1+)&#x2028; IAT 2+ 46/M C/III 58 CHOP(8), HD-CTX, aPBSCT Unmutated IgVH&#x2028; Normal Kariotype 38 10.1 DAT 4+&#x2028; (IgG 3+; C3d 1+)&#x2028; IAT − 56/M C/IV 64 FC, chl, fludarabine, RIC transplant Unmutated IgVH Zap-70 + CD38 −Del 17p, Del 13q 28 4.9 DAT 4+&#x2028; (IgG 4+)&#x2028; IAT 2+ 61/M B/II 108 Fludarabine, CHOP, INFa, chl/pdn Mutated IgVH&#x2028; Zap-70 +&#x2028; CD38 +&#x2028; Del 17p, +12 24 14.3 Negative M: male, Chl: chlorambucil, Pdn: prednisone, FC: fludarabine+cyclophosphamide, Ig: intravenous immunoglobulin, HD-CTX: high dose-cyclophosphamide, aPBSCT: autologous peripheral blood stem cell transplantation.

Use of Bendamustine in Chronic Lymphocytic Leukaemia Patients with Co-morbidities

2012 ◽  
Vol 08 (01) ◽  
pp. 52 ◽  
Author(s):  
Véronique Leblond ◽  
Keyword(s):  
Chronic Lymphocytic Leukaemia ◽  
Lymphocytic Leukaemia ◽  
Response Rate ◽  
Progression Free Survival ◽  
Standard Of Care ◽  
Complete Response ◽  
Best Supportive Care ◽  
Phase Iii ◽  
High Dose ◽  
Phase Iii Study

Chronic lymphocytic leukaemia (CLL) is the most common adult leukaemia and mainly affects older patients. First-line treatments for 'fit' (go go) and 'unfit' (no go) CLL patients are well defined, in the form of fludarabine–cyclophosphamide–rituximab (FCR) combination chemoimmunotherapy and best supportive care, respectively. However, the majority of CLL patients fall between these two extremes (slow go patients), nevertheless the standard of care for these patients is not well defined. Recent data suggest that bendamustine chemotherapy may be a good option in this group. In a recent Phase III study, significant improvements in overall response rate, complete response and progression-free survival were reported with bendamustine compared with chlorambucil. Chlorambucil plus rituximab has been shown to induce high responses in elderly CLL patients with a relatively low complete response rate. Bendamustine plus rituximab, and reduced-dose fludarabine plus cyclophosphamide plus high-dose rituximab have demonstrated promising efficacy, but have not been evaluated in elderly CLL patients. Several trials are also ongoing evaluating novel cytostatic agents, combination chemotherapy and chemoimmunotherapy regimens in elderly patients.

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