Kit Lu

A multigene array for measurable residual disease detection in AML patients undergoing SCT

AML is a diagnosis encompassing a diverse group of myeloid malignancies. Heterogeneous genetic etiology, together with the potential for oligoclonality within the individual patient, have made the identification of a single high-sensitivity marker of disease burden challenging. We developed a multiple gene measurable residual disease (MG-MRD) RQ–PCR array for the high-sensitivity detection of AML, retrospectively tested on 74 patients who underwent allo-SCT at the NHLBI in the period 1994–2012. MG-MRD testing on peripheral blood samples prior to transplantation demonstrated excellent concordance with traditional BM-based evaluation and improved risk stratification for post-transplant relapse and OS outcomes. Pre-SCT assessment by MG-MRD predicted all clinical relapses occurring in the first 100 days after allo-SCT compared with 57% sensitivity using WT1 RQ–PCR alone. Nine patients who were negative for WT1 prior to transplantation were correctly reclassified into a high-risk MG-MRD-positive group, associated with 100% post-transplant mortality. This study provides proof of principle that a multiple gene approach may be superior to the use of WT1 expression alone for AML residual disease detection.

A retrospective review of acupuncture use for the treatment of pain in sickle cell disease patients: Descriptive analysis from a single institution

Objectives:This retrospective study describes the use of acupuncture for adult sickle cell patients in a single institution. Materials and Methods:We identified 47 sickle cell disease patients referred for acupuncture at the National Institutes of Health between January 2005 and September 2011. All patients were enrolled in a Study of the Natural History of sickle cell disease and signed consent. We reviewed patient demographics, location of acupuncture treatment sessions (inpatient vs. outpatient), number of sessions received, sites of pain, patient pain reporting, and the use of other complementary therapies. Results:Of the 47 patients (60% women, median age 36 y) referred for acupuncture, 42 had homozygous SS disease (89%) and 5 had SC disease (11%). Over half of the patients (51%) reported >3 sites of pain. Only 24 patients (51%) underwent acupuncture treatment. Of those who elected not to receive acupuncture, a majority (87%) accepted some other forms of complementary therapies. Nine patients underwent only inpatient acupuncture for acute vaso-occlusive crisis. Eleven patients received only outpatient acupuncture treatment for chronic pain, and 4 patients received both inpatient and outpatient treatments. For the patients who received inpatient acupuncture treatment for acute vaso-occlusive crisis, there was a significant reduction of reported pain score immediately after acupuncture treatment with an average pain reduction of 2.1 points on the numeric pain scale (P<0.0001). Excluding the 2 outliers, 75% of patients (n=13) in the outpatient setting described their pain as improved compared with prior session. Discussion:To our knowledge, this is the largest retrospective review of acupuncture use in the sickle cell population. This analysis describes the use of acupuncture and raises the possibility of its use as an adjuvant for pain management in this population. Future clinical trials are needed to evaluate acupuncture’s efficacy and effectiveness for pain management in different treatment settings and for various types of pain etiologies among the sickle cell population.

Contrast enhanced cardiac CT reveals coronary artery disease in 45% of asymptomatic allo-SCT long-term survivors.

Contrast enhanced cardiac CT reveals coronary artery disease in 45% of asymptomatic allo-SCT long-term survivors

Clinical and biological predictors of outcome following relapse of CML post-allo-SCT.

While there are now fewer allogeneic stem cell transplants (allo-SCT) performed for chronic myeloid leukemia (CML), leukemic relapse post-transplant remains a persistent problem. To better define clinical and biological parameters determining post-relapse outcome, we studied 59 patients with CML relapsing after HLA-identical sibling allo-SCT between 1993 and 2008. Eighteen (30.5%) were transplanted in advanced phase and 41(69.5%) in chronic phase. With a median follow up from relapse of 7.9 years, 5-year post-relapse survival (PRS) was 62%. Multivariate analysis found disease status at transplant, time to diagnosis of relapse from transplant, and pre- transplant TKI use as significant factors associated with PRS. Analysis of BCR-ABL transcript expression in the hematopoietic progenitor compartment was performed in 36 patients (22 relapsed, 8 non-relapsed, and 6 TKI alone controls). Patients with BCR-ABL expression in their early hematopoietic stem cell compartment (HSC: Lineage−CD34+CD38-CD90+) had worse survival irrespective of the disease status. We conclude disease status remains the strongest clinical prognostic factor for PRS in CML following allo-SCT. The persistence of BCR-ABL expression in the progenitor cell compartment in some patients after SCT emphasizes the need to target CML-leukemia stem cells.Although there are now fewer allo-SCTs performed for CML, leukemic relapse post transplant remains a persistent problem. To better define clinical and biological parameters determining postrelapse outcome, we studied 59 patients with CML relapsing after HLA-identical sibling allo-SCT between 1993 and 2008. Eighteen (30.5%) were transplanted in advanced phase and 41 (69.5%) in chronic phase. With a median follow-up from relapse of 7.9 years, 5-year post relapse survival (PRS) was 62%. Multivariate analysis found disease status at transplant, time to diagnosis of relapse from transplant and pretransplant tyrosine kinase inhibitor (TKI) use as significant factors associated with PRS. Analysis of BCR-ABL transcript expression in the hematopoietic progenitor compartment was performed in 36 patients (22 relapsed, 8 non-relapsed and 6 TKI alone controls). Patients with BCR-ABL expression in their early hematopoietic stem cell compartment (Lineage−CD34+CD38−CD90+) had worse survival irrespective of the disease status. We conclude that disease status remains the strongest clinical prognostic factor for PRS in CML following allo-SCT. The persistence of BCR-ABL expression in the progenitor cell compartment in some patients after SCT emphasizes the need to target CML-leukemia stem cells.

Clinical comorbidity predictive measures in ex vivo T-cell-depleted allogeneic hematopoietic stem cell transplantation

Clinical comorbidity predictive measures in ex vivo T-cell-depleted allogeneic hematopoietic stem cell transplantation

Cellular immune profiling after sequential clofarabine and lenalidomide for high risk myelodysplastic syndromes and acute myeloid leukemia

Patients with high risk myelodysplastic syndromes (MDS) and acute myelogenous leukemia (AML) are commonly older with multiple co-morbidities, rendering them unsuitable for intensive induction chemotherapy or transplantation. We report preliminary cellular immune profiling of four cases receiving sequential clofarabine and lenalidomide for high risk MDS and AML in a phase I study. Our results highlight the potential of immune profiling for monitoring immune-modifying agents in high risk MDS and AML.

Atrial flutter associated with carboplatin administration.

Objective: To report a novel case of atrial flutter associated with carboplatin administration and review chemotherapy-related cardiac toxicities, focusing on platinum-containing compounds. Case Report: A 69-year-old man with extensive small cell lung cancer and asymptomatic cardiovascular and cerebrovascular disease was inconsistently adherent to his medication regimen. While undergoing carboplatin infusion, he developed atrial flutter. He had no other immediate arrhythmogenic causes of atrial flutter and the arrhythmia spontaneously reverted to sinus rhythm after 24 hours. His condition remained stable until he died 8 days later. The cause of death was unknown and the family declined postmortem examination. Discussion: Although this patients cardiac history and nonadherence to his medications may have increased his susceptibility to develop atrial arrhythmias, the Naranjo probability scale reveals a possible relationship between atrial flutter and Infusion of carboplatin. A literature search revealed other adverse cardiac events due to platinum compounds; however, to our knowledge, this case is the first to describe an association with atrial flutter. A definitive causal link cannot be determined, but this may have been the result of a direct arrhythmogenic effect of treatment or to a novel hypersensitivity reaction. Given the potential deleterious impact of drug-induced arrhythmias, we have reported this case to the Food and Drug Administration as a new adverse effect of carboplatin. Conclusions: Providers should consider cardiac monitoring during carboplatin infusion in patients with known cardiac disease or at high risk of cardiac complications.