Efficacy Of Cladribine Research Articles

Cladribine-Based Therapy for Acute Myeloid Leukemia in Child, Adolescent, and Early Young Adult Patients: The MD Anderson Cancer Center Experience.

Background: Cladribine-based combination chemotherapy has demonstrated promising efficacy in patients with relapsed/refractory adult acute myeloid leukemia (AML), prompting its increased utilization in the frontline; in pediatrics, it has been typically reserved for relapsed or refractory cases. While fludarabine has been used more commonly as a purine analog in intensive regimens, cladribine may be an important alternative. Methods: We performed a retrospective study at MD Anderson Cancer Center from January 2015 to July 2023, which included patients aged 1-21 years with refractory or relapsed AML who received cladribine outside of a transplant conditioning. Results: A total of 30 patients were included, with a median age of 20 years (range, 2-21), and 55% being male. Similar to adults, cladribine exhibited good tolerability in pediatric and adolescent patients, with the most common adverse events being febrile neutropenia and myelosuppression. The most common grade 3 or 4 adverse events included febrile neutropenia (55%) and sepsis (26%), and there were no treatment discontinuations due to adverse events. Among patients with a median number of 2 (0-7) prior treatments, the overall response rate (CR/CRi) was 45%, and median event-free and overall survival were 6 and 12 months, respectively. Disease progression resulted in 4 deaths within 30 days of treatment. Conclusions: Cladribine was tolerated in pediatrics. No new safety signals were seen with cladribine regimens in this cohort. Response assessment is limited due to the heavily pretreated cohort. Further prospective studies are warranted on the safety and efficacy of cladribine and establish its role in pediatric, adolescent, and early young adult patients with AML.

Efficacy of Cladribine, Low-Dose Cytarabine, and Venetoclax in Relapsed/Refractory Acute Myeloid Leukemia in a High-Risk Ethnically Diverse Cohort

Efficacy of Cladribine, Low-Dose Cytarabine, and Venetoclax in Relapsed/Refractory Acute Myeloid Leukemia in a High-Risk Ethnically Diverse Cohort

Safety and efficacy of Cladribine in real life sitting, Kuwait Experience (P8-3.014)

<h3>Objective:</h3> To study the effectiveness and the safety of Cladribine treatment in MS patients in a real-world clinical setting. <h3>Background:</h3> Cladribine was approved for treatment of multiple sclerosis (MS). Real-world data is very limited. <h3>Design/Methods:</h3> This observational, prospective study included MS patients who had at least one year follow-up after second course of Cladribine treatment. Baseline patient clinical and radiological characteristics recorded within one year prior to Cladribine initiation. The relapse rate, disability measures, radiological activity and adverse events at last visit were assessed. <h3>Results:</h3> A total of seventy-two patients, 59 (81.9%) were females, mean age 36.32 ±10.06 years old, mean disease duration 7.21±6.19. Most patients (n=32; 44.4%) were naïve to any treatment. Forty patients (55.6%) completed two courses of treatment. At the end of observational period, most of our cohort was relapse free (85% versus 25%; P&lt;0.001) and few had new T2 lesions (7.5% versus 70.8%; P&lt;0.001 and gadolinium enhancement 5% versus 66.7%; P&lt;0.001) in MRI compared to baseline. ARR was significantly reduced 0.15 ±0.36 versus 0.85±0.53; P&lt;0.01). Most of cohort 90% has no progression of disability. No evidence of disease activity 3 (NEDA-3) was achieved in 30 (75%) patients. It was achieved in 87.5% of naive patients versus 66.7% in patients who received prior disease modification drugs before Cladribine initiation. Infections 6 (n=6; 8.4%) lymphocytopenia (n=3; 4.2%), and elevated liver enzymes (n=1; 1.4%) were reported. <h3>Conclusions:</h3> The effectiveness and safety profile of cladribine in this study were consistent with data of phase 3 clinical trials. Early initiation of cladribine is associated with favorable outcome. <b>Disclosure:</b> Dr. AlMojel has nothing to disclose. Dr. Al-Hashel has nothing to disclose. Dr. Alroughani has received personal compensation in the range of $5,000-$9,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Biogen, Bayer, Novartis, Merck, Roche, Sanofi. Dr. Alroughani has received personal compensation in the range of $5,000-$9,999 for serving on a Speakers Bureau for Bayer, Biogen, Novartis, Merck, Roche, Sanofi. Dr. Ahmed has nothing to disclose.

Treatment with Cladribine Tablets Beyond Year 4: A Position Statement by Southeast European Multiple Sclerosis Centers.

Based on the results of the pivotal CLARITY study, cladribine tablets were approved for use in the European Union in 2017 as a high-efficacy therapy for highly active relapsing-remitting multiple sclerosis (MS). Cladribine tablets are used as an induction therapy: half of the total dose is given in year 1 and the other half in year 2. In the CLARITY Extension trials, repeating the dose routinely in years 3 and 4, was not associated with significantly improved disease control. However, there is very limited evidence on how to manage people with MS (pwMS) beyond year 4, which is increasingly important because more and more patients are now ≥ 4years after cladribine treatment. Overall, postapproval data show that treatment with two cladribine cycles effectively controls disease activity in the long term. However, there is general agreement that some pwMS with suboptimal response could benefit from retreatment. This study reviews the practical aspects of using cladribine tablets, summarizes the evidence from clinical trials and real-world studies on the safety and efficacy of cladribine, and proposes a treatment algorithm developed by expert consensus for pwMS previously treated with cladribine. In brief, we propose that additional courses of cladribine tablets should be considered in patients with minimal (no relapses, 1-2 new lesions) or moderate (1 relapse, 3-4 new lesions) disease activity, while significant disease activity (> 1 relapse, > 3 new lesions) or progression should warrant a switch to another high-efficacy treatment (HET). More evidence is needed to improve the treatment guidelines for pwMS who previously received cladribine.

Venetoclax, Cladribine Plus Low-Dose Cytarabine Achieved High Remission in Patients with Relapse/Refractory Acute Leukemia: Preliminary Results of a Phase II Study

Background: Patients with relapse/refractory acute leukemia often show resistance to conventional chemotherapy and have dismal prognosis. Salvage therapy using venetoclax combined with hypomethylating agents achieved an overall response rate of approximately 40% in relapsed/refractory (R/R) acute myeloid leukemia (AML) patients. Cladribine is an adenosine deaminase resistant analog of adenosine. The efficacy of cladribine and venetoclax in R/R acute leukemia (AL) has not been reported. Here, we report preliminary results of venetoclax, cladribine plus low-dose cytarabine (CAV regimen) in the treatment of R/R AL. This study was registered at ClinicalTrials.gov (NCT05190549). Methods: 30 patients were enrolled from March 2021 to May 2022 at the First Affiliated Hospital of Soochow University. 21 patients were diagnosed with R/R AML (6 patients with favorable risk, 2 patients of intermediate risk and 13 patients with high risk at diagnosis) (Table 1). Seven patients were diagnosed with R/R Philadelphia chromosome-negative B-cell acute lymphoblastic leukemia (ALL) (5 with high risk and 4 patients of unknown). The CAV regimen consisted of cladribine 5 mg/m2/day from day 1 to day 3 or day 5, cytarabine 20mg/m2, q12h for 7-10 days, venetoclax 100mg d1, 200 d2, 400 mg/day from day 3 to day 28 (The exact number of days is at the investigator's decision). Bone marrow evaluation were performed within 1 week at the end of treatment. Results: The median age of enrolled patients were 39 in AML and 35 in ALL. 13/21 (66.9%) of AML patients and 5/9 (51.6%) of ALL patients had high-risk cytogenetics at diagnosis. All patients showed early relapse (less than 12-months from CR1). After one cycle of the CAV regimen, the overall response rate (ORR=CR+CRi+MLFS+PR) for AML was 90.5%. The rate of CR/CRi/MLFS was 81% in AML and CR/CRi was 55.6% in ALL. The estimated 1-year overall survival (OS) in AML and ALL was 91.7% and 100%, respectively. The event-free survival (EFS) for AML and ALL were 74.9% and 87.5%, respectively. The median OS, EFS of one year for all 30 patients were not reached. There was no significant statistical difference of disease type in OS (P=0.162) and EFS (P=0.935). During the treatment with CAV regimen, 7 patients (33.3%) developed grade 1 to 2 elevated transaminases. 5 patients (23.8%) developed grade 1 to 2 nausea and vomiting and 1 patient(7.4%) developed grade 3 nausea and vomiting. 3 patients(14.3%) developed grade 1 to 2 skin pruritus and rash. During a median follow-up of 116-days, 3 patients died of disease relapse(Picture1,2). There was no CAV treatment-related mortality. Conclusion: The CAV regimen was an effective and safe salvage strategy in relapse/ refractory acute leukemia. Figure 1View largeDownload PPTFigure 1View largeDownload PPT Close modal

Systemic Mastocytosis: Response to the Efficacy of Cladribine(2-CdA) with Current Terminology and Approach.

Systemic Mastocytosis: Response to the Efficacy of Cladribine(2-CdA) with Current Terminology and Approach.

Venetoclax (Ven) added to intensive chemo with cladribine, idarubicin, and AraC (CLIA) achieves high rates of durable complete remission with low rates of measurable residual disease (MRD) in pts with newly diagnosed acute myeloid leukemia (AML).

7539 Background: Ven is a BCL2 inhibitor that is approved in combination with lower intensity therapy for pts with newly diagnosed AML who are ineligible for intensive chemo. We previously reported the safety and efficacy of cladribine and araC with idarubicin in young and fit pts with AML. Here, we studied the combination of ven with the intensive CLIA regimen in newly diagnosed AML. Methods: Pts &lt; 65 yrs with newly diagnosed FLT3-wildtype AML were enrolled. Induction was cladribine 5 mg/m2 IV on D 1-5, followed by ara-C 1.5 g/m2 IV on D 1-5, idarubicin 10 mg/m2 IV D 1-3, and ven at an effective dose of 400mg PO on D2-8. There was no ramp up for ven and dose modifications for CYP3A4 inhibitors were made. Consolidation consisted of up to 5 more cycles of CLIA+Ven. All pts underwent baseline next generation sequencing and MRD testing by multiparameter flow cytometry at the time of response. Results: 18 pts are enrolled, with a median age of 50 yrs (range, 18-64). Baseline pt characteristics are in Table. 16 pts were evaluable for response and 2 are too early. 14 of 16 pts (88%) achieved a remission, including 10 (63%) complete remission (CR) and 4 (25%) CR with incomplete count recovery (CRi). The median time to response was 1 cycle and the median number of cycles given was 2 (1-5). 10 of the 14 responders (71%) had undetectable MRD at the time of remission. Both nonresponding pts had a complex karyotype and 1 had a TP53 mutation. With a median follow up of 4.5 months (0.2 – 11.2), none of the responding pts have relapsed. 8 of the 14 responders (57%) have received allogeneic stem cell transplant. The median survival has not been reached; the 6-month OS and RFS are 90% and 100%, respectively. Treatment was well tolerated, with 0% 4-week mortality. The median days to ANC ≥ 1 and Platelets ≥ 100 were 30 (19-49) and 26 (18-39), respectively. Tumor lysis syndrome was not seen. The most common adverse events were neutropenic fever, pneumonia, nausea, and liver transaminitis. Conclusions: The addition of ven to CLIA was safe and effective in newly diagnosed pts with AML. The combination was not associated with early mortality or prolonged myelosuppression, but did result in high rates of durable MRD negative remissions. Clinical trial information: NCT02115295 . [Table: see text]

The Efficacy of Cladribine (2-CdA) in Advanced Systemic Mastocytosis

Systemic mastocytosis (SM) is a rare clonal disorder with multi-organ involvements and shortened life expectancy. To date, no curative treatment for SM exists. Cladribine (2-CdA) is a purine analogue showing activity against neoplastic mast cells and its use was found to be effective in some patients with SM. Nine patients (six males and three females) with advanced SM at median age of 63 years (range 33–67) who received at least one course of 2-CdA were included in a retrospective analysis. Study patients were classified as having aggressive SM (ASM; n = 7) and SM with an associated hematological neoplasm (SM-AHN; n = 2). The “C” findings were as follows: (1) absolute neutrophil count (ANC) < 1 × 109/l (n = 1) and/or hemoglobin level < 10 g/dl (n = 4) and/or platelet count < 100 × 109/l (n = 4); (2) hepatomegaly with ascites (n = 4); (3) skeletal involvement (n = 2); (4) palpable splenomegaly with hypersplenism (n = 3) and (5) malabsorption with weight loss (n = 5). Treatment consisted of 2-CdA at dose 0.14 mg/kg/day intravenously over a 2-h infusion for 5 consecutive days. Median dose per cycle was 45 mg (range 35–60). Median number of cycles was 6 (range 1–7). Overall response rate (ORR) was 66% (6/9 pts) including three partial responses and three clinical improvements. ORR was 100% and 66% for SM-AHN and ASM, respectively. Median duration of response was 1.98 years (range 0.2–11.2). At the last contact, five patients died, four have little disease activity, but remain treatment- free. 2-CdA seems to be beneficial in some patients with SM, however the response is incomplete.

Long-term follow-up of Cladribine, high-dose Cytarabine, and Idarubicin as salvage treatment for relapsed acute myeloid leukemia and literature review.

Outcome for relapsed acute myeloid leukemia (AML) is poor. Cladribine has activity in AML, and an enhancing effect on other cytostatic drugs thus may help overcome resistance. Here, we present the final analysis of our phase II trial evaluating safety and efficacy of cladribine, cytarabine, and idarubicin (CAI) in relapsed AML. Patients with relapsed AML after at least 6months remission received two courses of CAI. After 9 patients, prolonged neutropenia prompted protocol change (omission of idarubicin in 2nd course and dose-reduction of cytarabine). Primary endpoints were remission rate and safety. Twenty patients received treatment, fourteen one, and six two courses CAI/CA. After first course, complete remission (CR/CRi) was achieved in 60%. Most frequent toxicity was infection. Median OS was 8.8months in all patients and 21.1months in those with CR. Nine patients (48%) proceeded to allogeneic stem cell transplantation (allo-SCT), four of those are still alive and in CR, accounting for a 5-year survival rate of 55% of transplanted patients. Cladribine, cytarabine, and idarubicin in relapsed AML is feasible and induces good response rates. As expected, infections are the most important complication. However, combined with allo-SCT, long-term survival can be achieved in a substantial number of patients.

Efficacy and Safety of Intravenous Cladribine in Patients with Rapidly Evolving or Early Secondary Progressive Multiple Sclerosis.

BackgroundMultiple sclerosis (MS) is an autoimmune and demyelinating inflammatory disease that affects the central nervous system (CNS). The etiology of the disease remains unknown. Multiple theories highlight genetic, environmental, and infectious factors that may a role. MS is considered as the main cause of disability in young people. Cladribine, known chemically as (2-Chloro-2′-deoxyadenosine), is a purine analog chemotherapy used for hairy cell leukemia and other B-cell lymphomas. The goal of this study was to evaluate the safety and efficacy of cladribine in patients with rapidly evolving or early secondary progressive MS.MethodsThis observational, single-center, retrospective chart review at the MS Clinic in the Ottawa General Hospital, Ottawa, Canada. A total of 24 patients (median Expanded Disability Status Scale (EDSS) of 4.5) received cladribine (0.07 mg/kg/day) for four consecutive days every six months for ≥ 2 cycles with further cycles depending on lymphocyte recovery or disease activity to a maximum of eight cycles from 2005 until 2016 were included. Four patients who were already diagnosed with rapidly evolving or early secondary progressive multiple sclerosis (SPMS) were induced with cladribine. We evaluated relapse, EDSS, and magnetic resonance imaging (MRI) results.ResultsOut of 24 patients (ages ranging from 30 - 60), 80% were female. Median follow-up time was seven years. The mean relapse rate in the two years before patients were given cladribine was 1.25. Twenty patients had previously received multiple disease-modifying therapies (DMTs) (≥ 2) prior to receiving cladribine. Following cladribine, eight patients suffered 10 relapses (33.3% of the cohort). Annualized relapse rates (ARRs) were reduced from 1.25 to 0.42, which was statistically significant (p-value = 0.002). There was no mean difference in EDSS (p-value = 0.06): 16% deteriorated, 62% did not change, and 12.5% improved. New MRI activity (new T2 or Gad+ lesions) was noted in only seven of 24 patients. ConclusionParenteral cladribine reduced the relapse rate from 1.25 to 0.42, which was statistically significant (p-value = 0.002). MRI activity in patients with rapidly evolving or early secondary progressive multiple sclerosis had a reasonable safety profile.

Acute Myeloid Leukemia Induction with Cladribine: Effects of Age and Leukemia Risk

Background: Acute myeloid leukemia (AML) induction traditionally includes seven days of cytarabine and three days of an anthracycline (7+3). Co-administration of cladribine may increase efficacy of cytarabine. This rationale directed Saint Louis University (SLU) to adopt a regimen derived from the Polish Adult Leukemia Group (Holowiecki, JCO 2012) which adds five days of cladribine to idarubicin based 7+3 (IAC). We report the SLU experience with toxicity and survival following IAC induction. Additionally, we discuss the effects of IAC in patients 60 and older as an area of particular interest.Methods: Retrospective analysis of patients with newly diagnosed AML (APL excluded) and high-risk MDS who received IAC from January 2009 to September 2015. IAC was initiated as cytarabine 200mg/m2 by continuous infusion for seven days, idarubicin 12mg/m2 daily for three days, and cladribine 5mg/m2 for five days. Mortality and disease response were analyzed, with stratification by age and NCCN leukemia risk classification.Results: Of 107 patients, 57 patients (53%) were age 60 and older. By NCCN cytogenetic and molecular stratification, 21 (20%) had favorable risk; 43 (40%) intermediate risk; and 43 (40%) poor risk leukemia. Complete response (CR) occurred in 75 (70%) patients and CRi in an additional 9 patients (8%) for an overall response rate of 79% (see Table 1). At one year, 58% of patients were still alive with 47% (27/57) of patients ≥60 years and 72% (36/50) of those <60 years surviving (OR 2.8, 95% CI 1.3-6.4). When stratifying by NCCN risk, no deaths at one year occurred among the favorable risk group (0/21), but 16/43 (37%) and 28/43 (65%) occurred in intermediate and poor-risk strata, respectively (p<0.001 by chi-squared). Median overall survival was 17.2 months with mean follow-up of 32.8 months. Cox proportional hazard ratio (HR) for death were significant for age ≥60 compared to age <60 (HR 2.2, 95% CI 1.3-3.7). Additionally, HR for intermediate risk leukemia was 6.2 (95% CI 1.8-21) and for poor risk leukemia it was 11 (95% CI 3.4-36), when each were compared to favorable risk. Thirty-three (31%) of patients were known to have received an allogeneic transplant, of which 42% (14/33) were 60 and older.Adverse events: Overall, the treatment related mortality (TRM) (defined as death within the first 28 days) was 11%. Eleven of 12 TRM events occurred in patients ≥60 years (OR 12, 95% CI 1.5-94). Diarrhea occurred in 71% of patients with 46% enduring mucositis. Intensive care unit admission occurred in 23% overall, and infections were documented in 73% of patients. Most common infectious etiology was coagulase negative staph in 29% (23/78). For patients surviving to discharge (90/107), median hospitalization was 30 days post induction.Conclusions: Cladribine combined with cytarabine and idarubicin is an effective induction regimen for AML with high rates of CR, even in patients 60 and older. Our data show that NCCN leukemia risk is a better predictor of survival compared to age and that patients aged ≥60 years have better survival (lower HR for death) compared to those with intermediate or poor risk leukemia. Additionally, CR and 1 year overall survival with IAC are better than expected in the older cohort, however, TRM is elevated among those 60 and older. Higher intensity regimens in older patients may be justified in select patients, especially given the greater life expectancies enjoyed in the modern era. Several ongoing prospective trials investigating the safety and efficacy of cladribine in older patients will provide additional information to inform the use of IAC in older patients. [Display omitted] [Display omitted] DisclosuresNo relevant conflicts of interest to declare.

A phase I/II trial of reduced intensity allogeneic hematopoietic cell transplant for hematologic malignancies using cladribine, thiotepa and rabbit antithymocyte globulin

We conducted a phase I/II trial to assess the efficacy of cladribine, thiotepa and antithymocyte globulin as a reduced-intensity conditioning regimen for refractory or high-risk hematologic malignancy. The preparative regimen consisted of cladribine 5 mg/m2/day for 5 days, thiotepa 200 mg/m2/day for 3 days and ATG 3 mg/kg/day (day − 5) followed by allogeneic peripheral blood stem cell transplant. Twelve patients were transplanted from a human leukocyte antigen (HLA) matched family member. Two patients were treated at dose level I but both experienced grade IV dose limiting toxicities, and therefore the thiotepa dose was reduced to 133 mg/m2/day (dose level II). Only two of the next six patients experienced dose limiting toxicities. Median age was 46 years. At dose level II, the median time to neutrophil and platelet engraftment was 17 and 20 days, respectively. The incidence of acute and chronic graft-versus-host disease (GVHD) was 40% and 30%, respectively. Day + 100 non-relapse mortality was 0% and at 1 year was 20%. Median overall survival (OS) was 42 months and 2-year OS was 70%. Median progression-free survival (PFS) was 11 months and 2-year PFS was 40%. We conclude that the reduced-intensity conditioning regimen of cladribine, thiotepa and ATG achieved excellent donor chimerism with acceptable toxicity.

Efficacy of Cladribine, Cytarabine, G-CSF (Neupogen), Mitoxantrone (CLAG-M Regimen) Compared to Standard 3+7 (Anthracycline and Cytarabine) in Secondary Acute Myeloid Leukemia (sAML) After Azanucleosides Failure

Abstract 256 BACKGROUND:Several recent reports indicated low response rates (20–30%) and poor outcome with standard anthracycline and cytarabine (3+7) induction regimen for sAML arising from MDS after azanucleosides failure (Bello et al. Cancer 2011 Apr 117) (Jabbour et al, Cancer 2010 August 15,116) (Prebt et al, JCO 2011 July) (Lin et al, ASH 2010 #2913). CLAG-M is an effective regimen in treating relapsed/refractory AML including relapsed/refractory sAML. The CR rate for CLAG-M was reported as high as 58% (Wrzesien-Kus, Robak et al. Eur J Haematol 2008 Feb). We compared the efficacy of CLAG-M to standard 3+7 as induction strategy in sAML after azanucleosides failure. METHODS:This was a retrospective case-control study. Data were obtained from the Moffitt Cancer Center (MCC) electronic records. Patients (18 years of age and older) with sAML who received primary induction therapy with the CLAG-M regimen (Cladribine 5 mg/m2/d intravenous (IV) over 2 hours(hrs) days (d) 1–5, Cytarabine (Ara-C) 2 g/m2/day IV over 4 hrs starting 2 hrs after cladribine d1-5, Mitoxantrone (Novantrone)10mg/m2/d IV d1-3, Filgrastim (Neupogen) 300 mcg subcutaneous d0-5), were compared to matched controls (sAML, prior azanucleoside failure) who received standard 3+7 regimen ((Ara-C) 100 mg/m2/d civi d1-7 and Idarubicin 12 mg/m2/d iv d1-3) or (Cytarabine (Ara-C) 100 mg/m2/d civi d1-7 and Daunorubicin 45–60 mg/m2/d iv d1-3)). Baseline characteristics collected included age, gender, race, ECOG performance status, prior treatments, MDS IPSS score, leukocyte count and myeloblast percentage at induction, karyotype risk group, and duration between original MDS diagnosis and sAML. The primary endpoint was overall survival (OS), and secondary endpoints included response rates defined by standard AML response criteria and feasibility of allogeneic stem cell transplantation (allo SCT).Descriptive statistical analyses were utilized. Chi square analysis and t- test were utilized to compare categorical and continuous variables, respectively. Kaplan-Meier method was used to estimate OS and log rank test was used to compare the 2 groups. All data were analyzed using SPSS version 19.0 statistical software. RESULTS:Twenty five patients who received CLAG-M were compared to a control of 24 patients treated with 3+7 for sAML arising from MDS after azanucleosides failure treated at MCC. The baseline characteristics were similar in the two groups with no statistically significant differences noted except that more patients had an ECOG PS 1 in 3+7 group (table-1).Table 1Baseline Patient CharacteristicsVariableCLAG-M3+7P-ValueAgeAge > 60 years18 (72%)19 (79.2%)0.56GenderMale19 (76%)17 (70.8%)0.70RaceCaucasian23 (92%)20 (87%)0.48ECOG PS019 (76%)9 (40.9%)0.03216 (24%)11 (50%)0.32202 (9.1%)missing02 (9.1%)KaryotypeIntermediate11 (44%)14 (58.3%)Poor14 (56%)10 (41.7%)0.95WBC (k/μL)mean8.48.2Myleoblasts %mean35440.07Prior MDS IPSSInt-21 (4%)1 (4.3%)0.95High24 (96%)22 (95.7%)0.08missing01Hypomethylating Agent UseYes22 (88%)24 (100%)Duration between MDS and AML (mo)mean17130.44The CLAG-M cohort had a trend towards higher overall response rate (CR/CRi) 56% (N=14) compared to 29% (N=7) standard 3+7 (p=0.058). The median OS was 202 days (95%CI 97–307) versus 86 days (95%CI 30–142) (p=0.025) respectively in CLAG-M and 3+7 (Figure-1). The one year OS was 45% in CLAG-M group compared to 9% in 3+7 group. [Display omitted] Seven patients (28%) in the CLAG-M cohort versus 1 patient (4.2%) in the 3+7group received allo SCT (p= 0.024). The median OS was not reached for patients who proceeded to allo SCT in the CLAG-M cohort compared to 112 days for patients who did receive allo SCT in the 3+7 cohort (p=0.007). The mean duration of hospitalization was 33 days with CLAG-M compared to 41 days with 3+7 (p=0.08). CONCLUSION:CLAG-M as an induction regimen for sAML from MDS after azanucleosides failure was associated with better OS compared to standard 3+7 therapy. There was a trend towards higher response rates with the CLAG-M regimen which allowed more patients to proceed to allo SCT. These results need to be confirmed in a randomized prospective clinical trial. Disclosures:No relevant conflicts of interest to declare.

Cladribine Treatment in Two-Hour Intravenous Infusion for Previously-Treated Low Grade B-Cell Lymphoma : A Pilot Study

Cladribine is approved to be used in 24-hour continuous infusion for the treatment of low-grade lymphoma by the Ministry of Health, Labor and Welfare in Japan. Pharmacokinetic studies showed that the antitumor activity of cladribine by 2-hour infusion should be comparable to that given by continuous infusion. The safety and anti-tumor activity of short infusion of cladribine was shown in hairy cell leukemia, chronic lymphocytic leukemia and low-grade non-Hodgkin's lymphoma in Europe. We therefore underwent a pilot study to confirm the safety and efficacy of cladribine given by 2-hour infusion for Japanese patients with relapsed or refractory indolent B-cell lymphoma. Cladribine at a dose of 0.09 mg/kg was administered in 2-hour intravenous infusion for 5 consecutive days. The treatment was repeated at a 28-day interval for at least 2 cycles, and its efficacy and toxicity were investigated. Fourteen patients were entered into this study. Eight patients (57%) responded to cladribine, including 2 (14%) complete response (CR) and 6 (43%) partial response (PR). The median duration of response was 20+ and 21+ months for CR, and 12 months ranging from 3 to 34 months for PR, respectively. Grade 3 or 4 neutropenia and lymphocytopenia occurred in 43% and 71% of patients, respectively, but there was no febrile neutropenia or opportunistic infection associated with cladribine treatment. No other adverse events greater than grade 3 were encountered. The tumor response and degree of toxicity were comparable with those observed in cladribine treatment given by continuous infusion at a same dose. Cladribine can be administered in 2-hour infusion in an outpatient clinic and is therefore quite convenient for patients.