MTD 113-070A User Manual download pdf

January 2012, Vol. 19, No. 1 Cancer Control 37

Introduction

Although recent advances in ﬁ rst-line therapy of chronic

lymphocytic leukemia (CLL) have prolonged the dura-

tion of ﬁ rst remission, patients eventually experience

disease progression, with limited therapeutic options.

1,2

In general, patients with asymptomatic relapsed dis-

ease should be followed expectantly, and indications

From the Department of Malignant Hematology at the H. Lee Mofﬁ tt

Cancer Center & Research Institute, Tampa, Florida.

Submitted May 20, 2011; accepted October 3, 2011.

Address correspondence to Javier Pinilla-Ibarz, MD, PhD, Department

of Malignant Hematology, Mofﬁ tt Cancer Center, 12902 Magnolia

Drive, Tampa, FL 33612. E-mail: Javier.Pinilla@mofﬁ tt.org

Dr Veliz reports no signiﬁ cant relationship with the companies/

organizations whose products or services may be referenced in this

article. Dr Pinilla-Ibarz receives

honoraria from GlaxoSmithKline

Corp, Genentech Inc, and Cephalon Inc.

Gracia Dayton. City Snails. Watercolor on paper, 13⬙ × 22⬙.

Since CLL remains incurable with

standard therapies due to

development of disease refractoriness

continued research is needed to

develop improved treatment

outcomes for patients with CLL.

Treatment of Relapsed or Refractory

Chronic Lymphocytic Leukemia

Marays Veliz, MD, and Javier Pinilla-Ibarz, MD, PhD

Background: Recent advances in the treatment of chronic lymphocytic leukemia (CLL) have moved beyond

the traditional use of alkylating agents and purine analogs into regimens combining these two chemotherapy

classes with monoclonal antibodies.

Methods: This article reviews treatments options for patients with relapsed or refractory CLL.

Results: Several studies have investigated novel agents in treating patients with 17p deletion, TP53 mutation,

and ﬂ udarabine-refractory CLL, as well as patients with suboptimal response to intense treatment. These

investigational agents include rituximab, alemtuzumab, ofatumumab, bendamustine, high-dose methylprednisolone,

lenalidomide, lumiliximab, cyclin-dependent kinase inhibitors, small modular immunopharmaceuticals, Bcl-2

inhibitors, and histone deacetylase inhibitors. While these newer drugs and combination therapies have shown

promise as treatment options for CLL, additional studies are needed to determine the immunosuppression, toxicities,

and infections associated with their use.

Conclusions: Despite improvement in initial overall response rates, most patients relapse and require further

treatment. CLL remains incurable with standard therapies due to development of disease refractoriness. As such,

novel approaches such as those noted above warrant continued research to improve outcomes for patients with CLL.

for reinitiation of treatment should follow the same

guidelines of the National Cancer Institute (NCI) and

the International Workshop on Chronic Lymphocytic

Leukemia (IWCLL) for these patients as for previously

untreated patients.

3,4

Treatment selection of relapsed disease depends on

a variety of factors, including patient age, performance

status, duration of response to initial therapy, type of

prior therapy, disease-related manifestations, and genetic

abnormalities within the CLL cells. In most cases, ﬁ rst-

line therapy can be repeated if the duration of response

has lasted more than 1 year. On the other hand, treat-

ment decisions are more challenging in patients with

therapy-refractory disease or with the 17p deletion and

TP53 mutation. Fluorescence in situ hybridization (FISH)

imaging should be performed in all patients to deter-

mine cytogenetic abnormalities before making treatment

1 2 3 4 5 6 ... 16 17

Summary of Contents

Page 1 - Chronic Lymphocytic Leukemia

January 2012, Vol. 19, No. 1 Cancer Control 37IntroductionAlthough recent advances in ﬁ rst-line therapy of chronic lymphocytic leukemia (CLL) have p

Page 2 - Rituximab as a Single Agent

46 Cancer Control January 2012, Vol. 19, No. 1vivo.116 Following initial phase I studies showing that a 30-minute intravenous bolus followed by 4-ho

Page 3 - Chemoimmunotherapy

January 2012, Vol. 19, No. 1 Cancer Control 47of commonly used CLL agents including ﬂ udarabine, rituximab, and alemtuzumab.127 Clinically, oblimers

Page 4 - Alemtuzumab

48 Cancer Control January 2012, Vol. 19, No. 1to the study drug. CAL-101 reduced lymphadenopathy in all of the patients, and 91% achieved a lymph no

Page 5

January 2012, Vol. 19, No. 1 Cancer Control 49that prevented repeated dosing. Several patients had evidence of antitumor activity following treatmen

Page 6 - Ofatumumab

50 Cancer Control January 2012, Vol. 19, No. 1 16. Bosch F, Ferrer A, López-Guillermo A, et al. Fludarabine, cyclophos-phamide and mitoxantrone in

Page 7 - Bendamustine

January 2012, Vol. 19, No. 1 Cancer Control 51 63. Montillo M, Tedeschi A, Ricci F, et al. Fludarabine, cyclophospha-mide, and alemtuzumab (FCC) i

Page 8 - High-Dose Methylprednisolone

52 Cancer Control January 2012, Vol. 19, No. 1combined with ﬂ udarabine, cyclophosphamide, and rituximab in patients with relapsed or refractory chro

Page 9 - Investigational Agents

January 2012, Vol. 19, No. 1 Cancer Control 53lymphocytic leukemia cells. Blood. 1999;94(4):1401-1408. 153. Aron JL, Parthun MR, Marcucci G, et al

Page 10 - Bcl-2 Inhibitors

38 Cancer Control January 2012, Vol. 19, No. 1decisions since many patients with relapsed CLL often acquire high-risk chromosomal abnormalities such

Page 11 - Kinase-Targeted Therapy

January 2012, Vol. 19, No. 1 Cancer Control 39mg/m2, 43% at a dose of 1,000 mg/m2 to 1,500 mg/m2, and 75% for those treated at the highest dose of 2,

Page 12 - Dasatinib

40 Cancer Control January 2012, Vol. 19, No. 1was administered to 28 patients with recurrent or re-fractory CLL. The regimen showed an OR rate of 78

Page 13 - Conclusions

January 2012, Vol. 19, No. 1 Cancer Control 41frequently occur after intravenous administration.56 The study included 103 patients with ﬂ udarabine-

Page 14

42 Cancer Control January 2012, Vol. 19, No. 1alemtuzumab to the combination (CFAR).65 The regimen consisted of cyclophosphamide 250 mg/m2 on days 3

Page 15

January 2012, Vol. 19, No. 1 Cancer Control 43mg doses), followed by 2,000-mg doses once monthly for 2 years. The study is expected to enroll 25 pat

Page 16

44 Cancer Control January 2012, Vol. 19, No. 177.4% and the CR rate was 14.5%. The OR rate was 92.3% for the subset with del(11q), 100% for trisomy

Page 17

January 2012, Vol. 19, No. 1 Cancer Control 45zumab in patients with ﬂ udarabine-refractory disease, for which OR rates are approximately 30% and CRs

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