American Journal of Hematology

Goodnough, Lawrence Tim; Shander, Aryeh S.

doi: 10.1002/ajh.21870pmid: 20890909

Hess, Gregory; Nordyke, Robert J.; Hill, Jerrold; Hulnick, Scott

doi: 10.1002/ajh.21837pmid: 20976794

Cancer patients frequently develop chemotherapy‐induced anemia, which can be treated with erythropoiesis‐stimulating agents. These agents have shifted the standard of chemotherapy‐induced anemia treatment away from the previous mainstay of red blood cell transfusions. In July 2007, the Centers for Medicare and Medicaid Services issued a National Coverage Decision restricting reimbursement for erythropoiesis‐stimulating agents to those chemotherapy patients who have hemoglobin levels <10 g/dL at initiation of therapy. This decision was hypothesized to place a greater reliance on transfusions for chemotherapy‐induced anemia treatment. This observational study examined transfusions and erythropoiesis‐stimulating agent utilization rates within defined episodes of chemotherapy care using electronic medical records from seven practices consisting of 39 sites of care across seven states. We compared the frequency of myelosuppressive chemotherapy treatment, erythropoiesis‐stimulating agent administrations, and red blood cell transfusions before and after the National Coverage Decision in oncology patients with chemotherapy‐induced anemia. Although exposure to myelosuppressive chemotherapy was not different, erythropoiesis‐stimulating agent administrations significantly decreased and blood transfusions significantly increased after implementation of the National Coverage Decision. The 31% increase in transfusions for patients aged 65 years and older was significant (P = 0.007) and higher than the 8% increase for patients younger than 65 years (P = 0.358). Changes in practice patterns for chemotherapy‐induced anemia treatment that followed the Centers for Medicare and Medicaid Services reimbursement decision for erythropoiesis‐stimulating agents seem to be impacting practice patterns. Further research is necessary to determine whether these changes represent a widespread and durable shift in patient treatment. Am. J. Hematol., 2010. © 2010 Wiley‐Liss, Inc.

Terrell, Deirdra R.; Vesely, Sara K.; Hovinga, Johanna A. Kremer; Lämmle, Bernhard; George, James N.

doi: 10.1002/ajh.21833pmid: 20799358

Thrombotic thrombocytopenic purpura (TTP) and hemolytic‐uremic syndrome (HUS) represent multiple disorders with diverse etiologies. We compared the gender and race of 335 patients enrolled in the Oklahoma TTP‐HUS Registry across 21 years for their first episode of TTP or HUS to appropriate control groups. The relative frequency of women and white race among patients with TTP‐HUS‐associated with a bloody diarrhea prodrome and the relative frequency of women with quinine‐associated TTP‐HUS were significantly greater than their control populations. The relative frequency of women and black race among patients with idiopathic TTP and TTP‐associated with severe ADAMTS13 deficiency was significantly greater than their control populations. The relative frequency of black race among patients who had systemic lupus erythematosus (SLE) preceding TTP was significantly greater than among a population of patients with SLE, and the relative frequency of black race among patients with other autoimmune disorders preceding TTP was significantly greater than their control population. No significant gender or race disparities were present among patients with hematopoietic stem cell transplantation‐associated thrombotic microangiopathy, TTP associated with pregnancy, or TTP associated with drugs other than quinine. The validity of these observations is supported by the enrollment of all consecutive patients across 21 years from a defined geographic region, without selection or referral bias. These observations of different gender and race disparities among the TTP‐HUS syndromes suggest the presence of different risk factors and may serve as starting points for novel investigations of pathogenesis. Am. J. Hematol., 2010. © 2010 Wiley‐Liss, Inc.

Abdulmalik, Osheiza; Safo, Martin K.; Seeholzer, Steven H.; Asakura, Toshio; Hasbrouck, Nicole C.; Russell, J. Eric

doi: 10.1002/ajh.21831pmid: 20872549

Hb Baden (β18Val→Met) is a rare variant hemoglobin that has never been functionally or clinically characterized. We describe a Hb Baden heterozygote who exhibits normal growth and development, as well as age‐ and gender‐appropriate hematological values. Surprisingly, in vitro analyses demonstrate that Hb Baden is relatively unstable and exhibits an abnormally high affinity for O2. These properties are likely to affect the physiologies of individuals who inherit the βBaden mutation in trans to a determinant for either a functionally relevant hemoglobinopathy or a mild thalassemia. The data also provide insights into the function of the A‐helix/AB‐segment of β globin, supporting a structural model in which this poorly understood region serves as a scaffold that fixes the positions of other helices that directly impact β‐globin function. Am. J. Hematol., 2010. © 2010 Wiley‐Liss, Inc.

Schuster, Steven R.; Rajkumar, Sundararajan Vincent; Dispenzieri, Angela; Morice, William; Aspitia, Alvaro Moreno; Ansell, Stephen; Kyle, Robert; Mikhael, Joseph

doi: 10.1002/ajh.21845pmid: 20842638

IgM multiple myeloma (MM) and Waldenstrom's macroglobulinemia (WM) are two distinct hematologic entities with the common finding of an IgM monoclonal gammopathy. Distinguishing these two diagnoses is critical as the approach to therapy is different. A priori, we defined IgM MM as a symptomatic clonal plasma cell proliferative disorder characterized by an IgM monoclonal protein (regardless of size), 10% or more plasma cells on bone marrow biopsy, plus the presence of lytic bone lesions and/or translocation t(11;14). Twenty‐one patients met this definition of IgM MM. All 21 patients had lytic bone lesions. Of the 16 evaluated with FISH, 6 (38%) demonstrated t(11;14). Median overall survival was 30 months, which is similar to non‐IgM myeloma patients treated during this period and shorter than what would be expected for WM. In this, the largest series of patients with IgM MM, we describe the clinical features and prognosis of patient with IgM MM using a strict definition for the disease. The subset of patients without lytic lesions or t(11;14) but with immunophenotypic features suggestive of MM need further study. Am. J. Hematol., 2010. © 2010 Wiley‐Liss, Inc.

Kim, Dong Hwan (Dennis); Sriharsha, Lakshmi; Jung, Chul Won; Kamel‐Reid, Suzanne; Radich, Jerald P.; Lipton, Jeffrey H.

doi: 10.1002/ajh.21850pmid: 20882527

Early recognition of high‐risk patient is important to improve long‐term outcomes following imatinib therapy for chronic myeloid leukemia (CML). Some controversy surrounds the question, which of short‐term response parameters at which time‐point, including complete cytogenetic response (CCyR) or major molecular response (MMR) at 6 or 12 months, is the best predictor for treatment outcomes. In this comprehensive analysis, we adopted landmark analysis method, time‐dependent Cox's proportional hazard model, and receiver‐operating characteristics (ROC) method to analyze time‐to‐response parameter as predictor of long‐term outcomes in 187 chronic phase (CP) CML patients. Regardless of the methods of analysis, earlier achievement of short‐term response such as CCyR or MMR could predict the higher probability of achieving better interim outcome (such as treatment failure or loss of response [LOR]). Similar to the findings from other studies, our ROC analysis provided cutoff time points for MMR (18–36 months) and CCyR (6–12 months) that were the best predictors for LOR or treatment failure, which can be an indirect evidence supporting the ELN recommendation. The patient who achieves short‐term response rapidly will have a lower risk of losing response or failing after imatinib therapy in CML patients. Am. J. Hematol., 2010. © 2010 Wiley‐Liss, Inc.

Eleutherakis‐Papaiakovou, Evangelos; Kostis, Evangelos; Migkou, Magda; Christoulas, Dimitrios; Terpos, Evangelos; Gavriatopoulou, Maria; Roussou, Maria; Bournakis, Evangelos; Kastritis, Efstathios; Efstathiou, Eleni; Dimopoulos, Meletios A.; Papadimitriou, Christos A.

Frezzato, Maurizio; Giaretta, Ilaria; Madeo, Domenico; Rodeghiero, Francesco

doi: 10.1002/ajh.21854pmid: 20872553

The pathogenesis of chronic lymphocytic leukemia (CLL) has not been fully elucidated. Moreover, the time required for the initial B lymphocyte IGH gene rearranged clone to manifest as a clinical entity remains unknown. We searched for previous IGH gene rearranged B lymphocyte clones in healthy people who developed CLL and estimated the time for the clone to become clinically detectable. To this aim, we identified all incident cases of CLL diagnosed in a cohort of 15,055 healthy subjects aged 18–65 years enrolled in a prospective survey on thrombophilia. Seven CLL cases were identified at a median follow‐up of 54 months (range, 18–89). The estimated incidence was 0.46 cases/10,000 person‐years (CI: 0.17–1.00). A PCR was performed to detect IGH gene rearrangement at enrollment and at CLL diagnosis. Comparison was possible in six subjects. In five, the same IGH gene rearrangement and gene sequence were already present 39–89 months before CLL diagnosis. A mutated status was identified in four of five cases. The median age at diagnosis was 66.2 years, and all subjects were asymptomatic. Two patients expressing the IGHV1‐69 gene with an unmutated status required treatment 16 and 40 months after diagnosis. The IGHV4 family genes were rearranged in the remaining cases, all showing a mutated status. No additional rearrangements or mutations in the rearranged gene were found during follow‐up. An identical clonal IGH gene rearrangement may precede CLL diagnosis by several years. Am. J. Hematol., 2010. © 2010 Wiley‐Liss, Inc.

Goto, Naoe; Hara, Takeshi; Tsurumi, Hisashi; Ogawa, Kengo; Kitagawa, Junichi; Kanemura, Nobuhiro; Kasahara, Senji; Yamada, Toshiki; Shimizu, Masahito; Nakamura, Mitsuhiro; Matsuura, Katsuhiko; Moriwaki, Hisataka

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Kohrt, Holbrook E.; Patel, Samit; Ho, Michelle; Owen, Terri; Pollyea, Daniel A.; Majeti, Ravindra; Gotlib, Jason; Coutre, Steve; Liedtke, Michaela; Berube, Caroline; Alizadeh, Ash A.; Medeiros, Bruno C.

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