Delaying pegaspargase during induction in adults with acute lymphoblastic leukaemia is associated with lower risk of high-grade hepatotoxicity without adversely impacting outcomes.

Pegaspargase is a key drug for the treatment of younger adults with acute lymphoblastic leukaemia (ALL). Pegaspargase-associated hepatotoxicity is most common during induction, and its incidence increases with age and body mass index (BMI). We hypothesized that the delayed administration of pegaspargase during induction is associated with lower risk of hepatotoxicity while retaining efficacy.

Shorter long-term post-transplant life expectancy may be due to prior chemotherapy for the underlying disease: analysis of 3012 patients with acute myeloid leukemia enrolled on 9 consecutive ECOG-ACRIN trials.

Several studies reported that patients with acute myeloid leukemia (AML) who remain in long-term remission after allogeneic or autologous transplant have a shorter life expectancy, compared to the general population. However, little is known about the life expectancy of adult long-term survivors of AML who were treated with chemotherapy alone without a transplant and there have been no comparisons with survival among the general population. The current study indicates that the life expectancy of AML patients who achieved and maintained CR for at least 3 years is shorter than expected for age in the US population.

Asparaginase: How to Better Manage Toxicities in Adults.

Purpose Of Review: This review aims to help oncologists who predominantly treat adults better understand and manage asparaginase associated toxicities and prevent unnecessary discontinuation or reluctance of its use.

Recent Findings: Given the data supporting the benefit of incorporating multiple doses of asparaginase in pediatric type regimens, it is prudent to promote deeper understanding of this drug, particularly its toxicities, and its use so as to optimize treatment of ALL. Although asparaginase is associated with a variety of toxicities, the vast majority are not life threatening and do not preclude repeat dosing of this important drug.

SOHO State of the Art Updates and Next Questions | Asparaginase-Understanding and Overcoming Toxicities in Adults with ALL.

The adoption of pediatric-inspired regimens in young adults with newly diagnosed acute lymphoblastic leukemia (ALL) has significantly improved their survival outcomes. Pediatric-inspired regimens in ALL rely profoundly on delivering adequate dosing of non-myelosuppressive drugs of which asparaginase, a bacterial derived agent, is a key component. Asparaginase therapy is associated with a spectrum of unique toxicities that are observed more frequently in adult patients compared to children with ALL, and this observation has contributed to the reluctance of adult oncologists to administer the drug to their patients.

Treatment of Patients with Acute Myeloid Leukemia with the Targeted Alpha-Particle Nanogenerator Actinium-225-Lintuzumab.

Purpose: The anti-CD33 antibody lintuzumab has modest activity against acute myeloid leukemia (AML). To increase its potency, lintuzumab was conjugated to actinium-225 (225Ac), a radionuclide yielding 4 α-particles. This first-in-human, phase I trial was conducted to determine the safety, pharmacology, and biological activity of 225Ac-lintuzumab.

Optimizing use of L-asparaginase-based treatment of adults with acute lymphoblastic leukemia.

Acute lymphoblastic leukemia (ALL) is a malignancy of lymphoid progenitor cells occurring at an annual incidence rate of approximately 1.1 to 2.1 per 100,000 person-years globally.

Immunophenotype of acute lymphoblastic leukemia in minorities- analysis from the SEER database.

Acute Lymphocytic Leukemia (ALL) is a malignancy that originates from immature lymphoid cells and is clinically established with flow cytometry through disease-specific markers. Variation between ethnic groups is an epidemiological aspect of ALL. Higher incidence rates have been observed in Latin American patients and ALL in Latinos carries a dismal prognosis.

Arsenic trioxide therapy predisposes to herpes zoster reactivation despite minimally myelosuppressive therapy.

Acute Promyelocytic Leukemia (APL) is a unique subtype of acute myeloid leukemia that is highly responsive to minimally myelosuppressive therapy with all-trans retinoic acid (ATRA) and arsenic trioxide (ATO). We and others have observed a higher than expected incidence of herpes zoster reactivation in APL patients treated with ATO. Memorial Sloan Kettering Cancer Center (MSKCC) has been using ATO since 1997 in all relapsed APL patients, and more recently has included it in our front-line APL regimens.

Pediatric-inspired chemotherapy incorporating pegaspargase is safe and results in high rates of minimal residual disease negativity in adults up to age 60 with Philadelphia chromosome-negative acute lymphoblastic leukemia.

Administration of pediatric-inspired chemotherapy to adults up to age 60 with acute lymphoblastic leukemia (ALL) is challenging in part due to toxicities of asparaginase as well as myelosuppression. We conducted a multicenter phase II clinical trial (NCT01920737) investigating a pediatric-inspired regimen, based on the augmented arm of the Children's Cancer Group 1882 protocol, incorporating 6 doses of pegaspargase 2000 IU/m2, rationally synchronized to avoid overlapping toxicity with other agents. We treated 39 adults ages 20-60 years (median, 38 years) with newly-diagnosed ALL (n=31) or lymphoblastic lymphoma (n=8).

Managing toxicities with asparaginase-based therapies in adult ALL: summary of an ESMO Open-Cancer Horizons roundtable discussion.

With recent prospective clinical trials that used paediatric regimens with multiple doses of pegylated form of asparaginase (PEG asparaginase) in adults reporting significantly improved survival compared with historical data with regimens that used less asparaginase, PEG asparaginase is increasingly being used in the treatment of adult acute lymphoblastic leukaemia (ALL). However, administering asparaginase still comes with its challenges, especially in adult patients. Therefore, it is important to understand how to manage its toxicities properly.

At three years, patients with acute lymphoblastic leukaemia are still at risk for relapse. Results of the international MRC UKALLXII/ECOG E2993 trial.

Late relapse [>3 years from complete remission (CR)] in acute lymphoblastic leukaemia (ALL), is unusual. Data from the MRC UKALLXII/ECOG E2993 trial are presented to evaluate the incidence and characteristics of late relapse in adult ALL. Of 1,909 patients, 1,752 (92%) achieved CR and among these 757 (43·2%) relapsed; 691 (91·3%) within three years and 66 (8·7%) beyond.

How I treat the toxicities of pegasparaginase in adults with acute lymphoblastic leukemia.

Administering asparaginase has always been problematic in adults because most general oncologists who treat adults are not familiar with its usage and toxicity. The toxicity profile of the drug is unique and is not observed with any other chemotherapy agent. Furthermore, asparaginase is almost exclusively used in acute lymphoblastic leukemia (ALL), which is a very rare cancer in adults.

Therapy-related acute lymphoblastic leukemia: Where do we stand with regards to its definition and characterization?

Acute lymphoblastic leukemia (ALL) arising in patients with prior malignancy is increasingly being reported. Although terms such as 'secondary' and 'therapy-related' have been interchangeably used to characterize these cases of ALL in a similar fashion to acute myeloid leukemia (AML), it must be noted that some reported cases have not had exposure to cytotoxic therapy and hence a causal relationship between the prior malignancy and subsequent ALL is difficult to establish. Therefore, the use of the term secondary ALL to describe such cases without exposure to cytotoxic therapy is preferably avoided and will not be discussed here.

Combination chemotherapy plus dasatinib leads to comparable overall survival and relapse-free survival rates as allogeneic hematopoietic stem cell transplantation in Philadelphia positive acute lymphoblastic leukemia.

Background: The Philadelphia chromosome is associated with a poor prognosis in acute lymphoblastic leukemia (ALL). While hematopoietic stem cell transplantation (HSCT) has been regarded as a favorable treatment option in adult Philadelphia-positive (Ph+) ALL, its benefit is less clear in the era of newer generation tyrosine kinase inhibitors (TKIs) like dasatinib.

Methods: This was a retrospective study that analyzed the outcomes of adult patients with Ph+ ALL treated with either combination chemotherapy plus dasatinib or combination chemotherapy plus dasatinib followed by allogeneic HSCT.

High-Dose Vincristine Sulfate Liposome Injection, for Advanced, Relapsed, or Refractory Philadelphia Chromosome-Negative Acute Lymphoblastic Leukemia in an Adolescent and Young Adult Subgroup of a Phase 2 Clinical Trial.

Purpose: A study of vincristine sulfate (VCR) liposome injection (VSLI) was conducted in patients with advanced, relapsed, or refractory, Philadelphia chromosome-negative acute lymphoblastic/lymphocytic leukemia (ALL). A retrospective subgroup analysis of the results was performed to evaluate the safety and efficacy of VSLI in the adolescent and young adult (AYA) patients.

Methods: Of the 65 patients treated in the pivotal Phase 2 Study HBS407 (NCT00495079), 44 patients were aged ≤39 years (median 27 [range 19-39] years) and were included in this analysis.

The emerging story of acute lymphoblastic leukemia among the Latin American population - biological and clinical implications.

Higher incidence rates and poor outcomes have been reported among Latin American patients (Latinos) with acute lymphoblastic leukemia (ALL). Distinct patterns in recent genomic studies allude to a predisposing genetic component. In this review, we critically examine the increasing amount of empirical information on the epidemiology, outcomes and genomics of Latinos with ALL.

Treatment of young adults with Philadelphia-negative acute lymphoblastic leukemia and lymphoblastic lymphoma: Hyper-CVAD vs. pediatric-inspired regimens.

For young adults with acute lymphoblastic leukemia, pediatric-based regimens are likely to provide the following when compared to hyper-CVAD regimens: better disease control, less hospitalization time, diminished acute toxicities, decreased financial cost, more quality-adjusted life years, and fewer adverse late effects, such as infertility, myelodysplasia, and second malignant neoplasms. There are also reasons to expect less cardiac and cognitive dysfunction after pediatric regimens. The improved quality and quantity of life associated with pediatric regimens renders them preferable to hyper-CVAD regimens for the treatment of Philadelphia-negative B-precursor or T-cell acute lymphoblastic leukemia and lymphoblastic lymphoma in young adults.

Very poor long-term survival in past and more recent studies for relapsed AML patients: The ECOG-ACRIN experience.

This study examines the long-term OS of relapsed AML patients who were enrolled to 9 successive ECOG-ACRIN trials for newly diagnosed AML, during 1984-2008. The objectives were to examine whether there is a trend of improvement in the survival of relapsed AML patients in the more recent studies and to search for prognostic factors that are associated with long-term OS after relapse. A total of 3012 patients were enrolled, 1779 (59.

Pediatric-Inspired Treatment Regimens for Adolescents and Young Adults With Philadelphia Chromosome-Negative Acute Lymphoblastic Leukemia: A Review.

Importance: The incidence of acute lymphoblastic leukemia (ALL) and lymphoblastic lymphoma (LBL) in adolescent and young adult (AYA) patients (age range, 15-39 years) in the United States is increasing at a greater rate than in younger or older persons. Their optimal treatment has been increasingly debated as pediatric regimens have become more widely used in the age group. This review compares the basic features of pediatric and adult chemotherapy regimens for ALL and LBL, recognizes and describes the challenges of the pediatric regimen, and suggests strategies to facilitate its adoption for AYAs with ALL and LBL.

Pegaspargase-related high-grade hepatotoxicity in a pediatric-inspired adult acute lymphoblastic leukemia regimen does not predict recurrent hepatotoxicity with subsequent doses.

Pediatric acute lymphoblastic leukemia (ALL) regimens, including higher cumulative asparaginase doses, have been investigated in adult ALL to improve outcomes. Preliminary results are promising, but hepatotoxicity rates with long-acting pegaspargase are greater in adults than children. However, adult pegaspargase-related hepatotoxicity is not as clearly defined despite being the commonest adult toxicity.

Phase 2 trial of a multivalent WT1 peptide vaccine (galinpepimut-S) in acute myeloid leukemia.

A National Cancer Institute consensus study on prioritization of cancer antigens ranked the Wilms tumor 1 (WT1) protein as the top immunotherapy target in cancer. We previously reported a pilot study of a multivalent WT1 peptide vaccine (galinpepimut-S) in acute myeloid leukemia (AML) patients. We have now conducted a phase 2 study investigating this vaccine in adults with AML in first complete remission (CR1).

Impact of Chromosomal Rearrangement upon DNA Methylation Patterns in Leukemia.

Genomic instability, including genetic mutations and chromosomal rearrangements, can lead to cancer development. Aberrant DNA methylation occurs commonly in cancer cells. The aim of this study is to determine the effects of a specific chromosomal lesion the translocation t(9:22), in establishing DNA methylation profiles in cancer.

A case of acute myeloid leukemia with e6a2 BCR-ABL fusion transcript acquired after progressing from chronic myelomonocytic leukemia.

Philadelphia (Ph) chromosome is a cytogenetic hallmark of chronic myeloid leukemia (CML). Most patients with CML harbor either the e13a2 or e14a2 BCR-ABL fusion product, while a small subset of the cases expresses e1a2 or e19a2 transcripts. We report a patient with chronic myelomonocytic leukemia (CMML), initially Ph chromosome negative at presentation, with rapid disease progression to acute myeloid leukemia (AML) and appearance of Ph chromosome and BCR-ABL e6a2, a very uncommon fusion transcript.