Follow-up Bone Marrow Examination Research Articles

Validation of a 12-color flow cytometry assay for acute myeloid leukemia minimal/measurable residual disease detection.

Acute myeloid leukemia (AML) minimal/measurable residual disease (MRD) by multicolor flow cytometry is a complex laboratory developed test (LDT), challenging for implementation. We share our experience in the validation of a 12-color AML MRD flow cytometry assay to meet stringent regulatory requirements. We worked under the guidelines of the CLSI HL62 publication, illustrated the details of the validation process that was tailored to uniqueness of AML MRD, and tested its clinical validity in 61 patients. The "trueness" was determined by correlating with concurrent molecular genetic testing and follow-up bone marrow examinations. Under assay specificity, we shared the details of panel design, analysis, and criteria for interpretation and reporting. The assay accuracy was assessed by testing known positive and negative samples and correlating with molecular genetic testing and follow-up bone marrow examination. The limit of detection (LOD) and limit of quantification (LOQ) were validated to a level between 0.01% and 0.1%, varied from the leukemia-associated immunophenotypes (LAIP) and the numbers of events obtained for analysis. Assay linearity, precision and carry over studies all met acceptable criteria. In the clinical validity test, the concordance was 93%, specificity 98% and sensitivity 83%. The most challenging aspects of the assay were the discrimination of pre-leukemic cells (persistent clonal hematopoiesis) or underlying myelodysplastic clones from AML MRD with immunophenotypic switch or subclone selection. The validation met all criteria and obtained FDA IDE (investigational device exemption) approval. This study provides ample technical and professional details in setting up the AML MRD flow cytometry assay and illustrates through the example of the "fit for purpose" validation process. We also highlight the need for further characterization of abnormal blasts bearing the potential for AML relapse.

Clinical Significance of Persistent Tumor in Bone Marrow during Treatment of High-risk Neuroblastoma.

The records of 63 high-risk neuroblastoma patients with bone marrow (BM) tumors at diagnosis were retrospectively reviewed. All patients received nine cycles of induction chemotherapy followed by tandem high-dose chemotherapy and autologous stem cell transplantation (HDCT/auto-SCT). Follow-up BM examination was performed every three cycles during induction chemotherapy and every three months for one year after the second HDCT/auto-SCT. BM tumor cells persisted in 48.4%, 37.7%, 23.3%, and 20.4% of patients after three, six, and nine cycles of induction chemotherapy and three months after the second HDCT/auto-SCT, respectively. There was no difference in progression-free survival (PFS) rate between patients with persistent BM tumor and those without during the induction treatment. However, after tandem HDCT/auto-SCT, the PFS rate was worse in patients with persistent BM tumor than in those without (probability of 5-yr PFS 14.7% ± 13.4% vs. 64.2% ± 8.3%, P = 0.009). Persistent BM tumor during induction treatment is not associated with a worse prognosis when intensive tandem HDCT/auto-SCT is given as consolidation treatment. However, persistent BM tumor after tandem HDCT/auto-SCT is associated with a worse prognosis. Therefore, further treatment might be needed in patients with persistent BM tumor after tandem HDCT/auto-SCT.

The First Korean Case of Moraxella osloensis Bacteremia in a Patient with Acute Myeloid Leukemia

The First Korean Case of Moraxella osloensis Bacteremia in a Patient with Acute Myeloid Leukemia

Rare Frameshift Mutation Cys475Tyrfs*11 in the BCR/ABL Kinase Domain Contributes to Imatinib Mesylate Resistance in 2 Korean Patients with Chronic Myelogenous Leukemia

Sang Hyuk Park, M.D., Hyun-Sook Chi, M.D., Mi-Ryang Kwon, M.D., Young-Uk Cho, M.D., Seongsoo Jang, M.D., and Chan-Jeoung Park, M.D.. Ann Lab Med 2012;32:452-4. https://doi.org/10.3343/alm.2012.32.6.452

Spontaneous changes in tumour cell dissemination to bone marrow in colorectal cancer

The study aimed to evaluate the incidence of disseminated tumour cells (DTCs) in bone marrow (BM) preoperatively and during follow up and to correlate these with established risk factors in patients with colorectal cancer. We prospectively studied BM in 57 patients using the anti-cytokeratin antibody A45-B/B3. The overall detection rate of DTCs was 23% with a similar detection rate through all stages of the disease. No significant association was found between the presence of DTCs and clinicopathological parameters. After a median follow up of 35.4 months, no differences were found in relapse and overall survival between patients with and without DTC preoperatively. In 31 of 45 patients with local disease, we performed a follow-up BM examination after 1 year. In 26% of the patients, the BM status had changed as compared with the preoperative finding. This is the first study to report the follow up of DTC in BM in colorectal cancer using the A45-B/B3 antibody. The presence of tumour cells in the preoperative BM had no impact on outcome. The BM status had changed after 12 months in a quarter of patients.

Pomalidomide Therapy in Myelofibrosis: 2-Year Follow-up of a Randomized Phase 2 Study.

Abstract 1904Poster Board I-927 BACKGROUND:Pomalidomide is an IMiDsó immunomodulatory drug that was created by chemical modification of thalidomide with the intent to reduce toxicity and enhance therapeutic activity. In a phase-2 randomized study of patients with myelofibrosis (MF), treatment with pomalidomide alone or in combination with a short course of prednisone was shown to be well tolerated and active in alleviating anemia ( JCO 2009). Herein, we report observations during the longer-term follow-up of those patients who had responded to a pomalidomide-containing treatment regimen. METHODS:Both primary and post polycythemia vera/essential thrombocythemia MF were included in the current study. Protocol eligibility criteria included absolute neutrophil count of × 109/L, platelet count of 50 × 109/L and hemoglobin level of < 10 g/dL. Patients with prior thalidomide or lenalidomide therapy were excluded from study participation. Response was assessed by the International Working Group for Myelofibrosis Research and Treatment criteria (IWG-MRT) (Blood. 2006). Pomalidomide was administered daily and continued indefinitely in responding patients. Prednisone was given for the first 3 months only, in a tapering dose schedule, starting at 30 mg/day. RESULTS:A total of 84 patients were enrolled from April 2007 through May 2008 and received treatment with pomalidomide alone 2 mg/day (n=22), pomalidomide 2 mg/day + prednisone (n=19), pomalidomide 0.5 mg/day + prednisone (n=22) or prednisone alone (n=21). Short-term toxicity details have previously been published (Tefferi et al. JCO 2009) and were remarkable for the lack of neuropathy and low prevalence of grade 3 or 4 myelosuppression (5–16%).Based on an intent-to-treat analysis, 16 (25%) of the 63 patients receiving pomalidomide alone or with a 3-month course of prednisone responded at a median of 1.8 months (range 0.9–6.9) from treatment initiation; all responses represented improvement in anemia with little or no effect on splenomegaly. Specifically, 12 of the 16 treatment responders became transfusion independent and the remaining 4 had a hemoglobin increase of > 2 g/dL (median best hemoglobin response = 11.9 g/dL; range 8.5–15.9). Responding patients usually displayed increases in platelet count but there was no consistent change in serum lactate dehydrogenase level.As of August 2009, ten (63%) of the 16 treatment responders were still in anemia remission and receiving pomalidomide therapy; median time on treatment was 19 months (range, 14–26) and median response duration was 17 months (range, 13-24). No new side effects emerged during this period. Six patients discontinued treatment because of either loss of response (n=5) or progressive splenomegaly/leukocytosis (n=1); 3 patients with continued anemia remission have had substantial increases in their spleen size, which qualifies as spleen progression per IWG-MRT. Among 9 patients with available cytogenetic information, all 3 with unfavorable karyotype relapsed while none of the 6 with favorable karyotype did.A small number of patients (n=7) had follow-up bone marrow examination at 1 to 2 years, at the discretion of their treating physician; none of these patients displayed any change in bone marrow fibrosis or JAK2V617F mutational status. Suppression of a monosomy 7 clone was documented in two patients. In one, the percentage of abnormal metaphases decreased from 90% to 15% after 11 months of treatment with pomalidomide but increased back to 100% four months later, when the patient relapsed while still on treatment. In the second patient, the percentage of abnormal metaphases was 65% at baseline, remained at 75% after 10 months of pomalidomide therapy, but decreased to 7% after one month of treatment discontinuation for relapse; a repeat examination in this patient after another 3 months (still off therapy) showed monosomy 7 and new additional abnormalities (including 4q21q25 deletion) in 65% of metaphases evaluated. CONCLUSION:Longer-term follow-up of pomalidomide-treated patients with myelofibrosis confirm the drug's favorable side effect profile. Also, the majority of treatment responders maintain their remission, which is exclusively anemia remission, for at least one year and several remain in remission after 2 years of therapy. The drug has limited effect on splenomegaly and progressive splenomegaly might occur in some patients despite continued remission in anemia. The presence of unfavorable cytogenetic abnormalities predicts relapse. Disclosures:Gale:Celgene: Employment.

P15INK4b Methylation Is Related to Blast Percentage, Thrombocytopenia, the Number of Lineages Involved in Cytopenia and Survival in Myelodysplastic Syndrome at the Time of Diagnosis: a Pyrosequencing Study.

Abstract 3793Poster Board III-729 IntroductionThe inactivation of tumor suppressor genes by promotor hypermethylation, particularly p15INK4b, is believed to contribute to the initiation and the progression of myelodysplastic syndromes (MDS). p15INK4b methylation was found to be more frequent in high-risk MDS (RAEB) at the time of diagnosis, and to be associated with progression to AML in the studies using methylation-specific PCR (MSPCR). We investigated if the quantity of p15INK4b methylation is related to International Prognosic Scoring System variables (IPSS) and survival in the myelodysplastic syndrome (MDS) patients and if the quantity of p15INK4b methylation reflects the bone marrow status (the percentage of blasts or the degree of dysplasia) of the patients under treatment with or without hypomethylating agents. Materials and MethodsThe study included 74 de novo MDS patients including 24 with follow-up bone marrow examination: 10 under treatment with hypomethylating agent and 14 under treatment with other than hypomethylating agent including stem cell transplantation (SCT). We pyrosequenced 63 base pairs of p15INK4b including 11 CpGs using PSQ96MA system (Biotage, Uppsala, Sweden), with the extent of CpG cytosine methylation assessed in terms of methylation index (MtI) and methylation level (MtL). ResultPatients with >5% bone marrow blasts had higher MtI and MtL (58.8% and 10.1%, respectively) than patients with <5% blasts (44.0% and 6.1%, p = 0.031 and p = 0.030, respectively). Methylation quantity was not associated with chromosomal aberrations. The MtI and MtL of patients with thrombocytopenia were higher than patients without thrombocytopenia (62.1% vs. 44.1%, p = 0.009, and 11.2% vs. 6.2%, p = 0.036, respectively); they were higher in patients with cytopenias in °Ã2 lineages than in patients with either unilineage or no cytopenia (56.5% vs. 39.4%, p = 0.055, and 9.8% vs. 4.1%, p = 0.036, respectively). The survival of patients with >50% MtI or >7% MtL was worse than patients with <50% MtI or <7% MtL (p = 0.023 and p = 0.031, respectively). Methylation quantity of p15INK4b did not correlate with the bone marrow status of the patients under treatment regardless of using hypomethylating agent or not. ConclusionUsing pyrosequencing, we showed that the quantity of p15INK4b methylation correlates with thrombocytopenia and blast percentage in MDS patients. Heavy p15INK4b methylation in MDS is associated with adverse survival. Methylation quantity of p15INK4b did not appear to reflect the bone marrow status of the patients under treatment regardless of the use of hypomethylating agent in this study, however, further study with controlled patient group is required to clarify this issue.Fig. 1. Heavy methylation of the p15INK4b promotor region is a prognostic factor for poor survival in MDS patients. (a) Kaplan-Meier curves of MDS patients with MtI >50% and patients with MtI <50% (mean survival time: 1118 days vs. 1864 days, respectively). (b) MDS patients with MtL >7% and patients with MtL <7% (738 days vs. 1804 days, respectively). [Display omitted] [Display omitted] Disclosures:No relevant conflicts of interest to declare.

Initial Evaluation of a 48-h Continuous Intravenous Infusion Weekly Regimen of ON 01910.Na in Advanced Myelodysplastic Syndrome (MDS).

Abstract 3815Poster Board III-751Following initial promising clinical results reported at ASH 2008 (Shenoy et al) in RAEB MDS and AML patients treated with the new investigational agent ON 01910.Na, we have initiated a phase 1/2 single arm escalating dose study in advanced MDS patients with a shorter schedule of administration of ON 01910.Na. The first 13 patients enrolled in our ongoing trial (6 high risk, 1 Intermediate-2 and 5 Intermediate-1 according to IPSS classification; 7 females/6 males, age range: 47-83ys), most of them having failed prior MDS therapies were administered ON 01910.Na as a 48 h continuous intravenous infusion weekly for 3 weeks of a 4-week cycle. Ten patients were treated at the 800 mg/m2/day dose level and 3 at the 1500 mg/m2/day dose level for 4 to 27+ weeks (1 to 6 four-week cycles). Most patients had grade 3 or 4 cytopenias at baseline. Overall the therapy was well tolerated and a few patients reported improvements of well being and pain relief. The most frequently reported adverse events were thrombocytopenia, neutropenia, anemia, fatigue and nausea. Serious adverse events were typical of this patient population and none of them was related to ON 01910.Na except for one case of neutropenia. Bone marrow blastic response was evaluated by bone marrow morphology. Five patients had a pretreatment blast count lower than 5% and no worsening of blast count was observed in the 3 patients who had follow-up bone marrow examination. Another six patients had more than 5% pretreatment bone marrow blasts. Among these patients, two had significant decreases in blast counts compared to pre-treatment values, while two showed stabilization and two progressed. Two patients had hematological improvements (neutrophil and erythroid responses). These results are encouraging and the trial is continuing.PatientBone Marrow BlastsHematological ImprovementPre-Treatment4-8 week Follow-up1<2%2%210-13%Death end 1st cycle31-2%Not Done (Platelet =4)420-30%30%N wk 10-185<5%3%63%Death end 2nd cycle7<5%1-2%825%11%910-13%15%*E wk 1-131035%Discontinued mid 2nd cycle (transplant)119%5%1210%2%1315%20%*16 week Follow-up: 25% blasts Disclosures:Wilhelm:Onconova: Employment.

Acute promyelocytic leukemia in early pregnancy with translocation t(15;17) and variant PML/RARA fusion transcripts

A 32-year-old pregnant woman in the 13th gestational week was brought to Severance Hospital with gum bleeding and easy bruising. Initial laboratory results revealed anemia and thrombocytopenia. In a peripheral blood smear, 81% of leukocytes were large, abnormal promyelocytes. Bone marrow aspiration showed a hypercellular marrow with packed leukemic promyelocytes, and chromosome study revealed a karyotype of 46,XX,t(15;17)(q22;q21)[10]/46,XX[10]. In addition, variant fusion transcripts of PML/RARA were detected in the marrow specimen. The patient was diagnosed with acute promyelocytic leukemia (APL) and was treated with all-trans retinoic acid (ATRA) and idarubicin. One month from the patient's initial diagnosis a follow-up bone marrow examination was performed, revealing complete remission (CR). We know of no previous reports of APL during pregnancy associated with variant PML/RARA fusion transcripts. Here, we describe a novel case of APL in a pregnant woman with a t(15;17) translocation and variant fusion transcripts.

Subcutaneous panniculitis-like T-cell lymphoma presenting with hemophagocytic lymphohistiocytosis and skin lesions with characteristic high-resolution ultrasonographic findings

Subcutaneous panniculitis-like T-cell lymphoma (SPTCL) is an unusual type of skin lymphoma, characterized by subcutaneous soft tissue infiltration with pleomorphic T-cells and benign macrophages that mimic panniculitis. Hemophagocytic lymphohistiocytosis is a rare but potentially fatal disorder which is thought to result from uncontrolled activation and proliferation of T-cells and excessive activation of macrophages. Hemophagocytic lymphohistiocytosis have been reported as the presenting feature in 37% of SPTCL patients. High-resolution ultrasonographic appearance of SPTCL with a characteristic finding has been described in only one patient. We report a 28-year-old woman with hemophagocytic lymphohistiocytosis presented with nonremitting fever, thrombocytopenia, hypofibrinogenemia, hyperferritinemia, increased serum levels of soluble interleukin (IL)-2 receptors and hemophagocytosis in bone marrow examination. Markedly elevated level of serum IL-18 was also demonstrated in our patient. The fever subsided and the ferritin level declined to normal after treatment with oral steroid and etoposide. No evidence of hemophagocytosis was revealed in a follow-up bone marrow examination. However, nonremitting high fever and panniculitis-like skin lesions over her back, arm, lower abdominal wall, and bilateral pretibial regions developed 1 month later. A high-resolution ultrasonography revealed thickening of the subcutaneous fat layer with homogeneous hyperechogenicity pattern and poor-defined margin over the skin lesions. An ultrasound-guided excision biopsy of the nodular lesion over left upper arm was performed and the histopathology showed neoplastic cells with hyperchromatic nucleoli, which extended from deep dermis to subcutaneous fat. The immunochemical stain showed a T-cell lineage of tumor cells. SPTCL was diagnosed and the skin lesions subsided gradually after treatment with anthracycline-based combination chemotherapy.

Phase II Study of the Combination of Low-Dose Thalidomide, Prednisone, and Etanercept (PET Regimen) in the Treatment of Anemia, Splenomegaly, and Constitutional Symptoms Associated with Myelofibrosis with Myeloid Metaplasia (MMM).

BACKGROUND: Disease manifestations in myelofibrosis with myeloid metaplasia (MMM) that require therapy include anemia, thrombocytopenia, hepatosplenomegaly, and constitutional symptoms. We have previously reported on the therapeutic value of low-dose thalidomide in combination with prednisone for the treatment of both anemia and thrombocytopenia in MMM (Blood 2003; 101:2534), and of etanercept (tumor necrosis factor-alpha antagonist) for alleviation of constitutional symptoms (Blood 2002; 99(6):2252). In the current study, we investigated the value of combining all three drugs (PET).METHODS: Study eligibility criteria included a histologically confirmed diagnosis of MMM and either severe anemia (hemoglobin < 10 g/dL) or symptomatic splenomegaly. Protocol treatment was initiated with 50 mg of oral thalidomide (THAL) daily, etanercept (ETAN) 25 mg subcutaneously twice-a-week, and a three month prednisone taper starting at 0.5 mg/kg/day for the first month followed by a 50% reduction for the second months and a further 50% reduction for the third and final month of treatment with prednisone. Patients with a demonstrable clinical response after three months were able to remain on thalidomide and etanercept.RESULTS: 15 patients were enrolled to the trial (median age 66 years, range, 54–77; 14 males). Twelve patients (80%) completed the planned three cycles (i.e. 3 months) of treatment (progression (n=2) and patient choice (n=1) accounted for the withdrawals), nine (60%) patients with evidence of response continued on an additional three months of THAL/ETAN alone (of which 3 progressed prior to study completion). At enrollment, 11 patients (73%) were anemic (7 (47%) were red cell transfusion dependent), 7 (47%) were at least moderately thrombocytopenic (platelet count < 100 x 109//L), and 6 had severe constitutional symptoms (night sweats or disease related fever). Anemia response were seen in 6 (of the 11 eligible; 54%) patients (2 in the non-transfusion dependent (sustained increases of 1.5 and 4.9 g/dL hemoglobin); 4 in transfusion dependent (1 transfusion independent, 3 >50% decrease in transfusion requirements)). All thrombocytopenic patients experienced an increase in platelet counts (median 55% increase (range(10–229) with 2 returning to the normal range (>150 x 109/L)). A greater than 50% decrease in organomegaly was documented in 3 patients with splenomegaly (25% of eligible), and 1 patient with hepatomegaly (25%). Constitutional symptoms resolved, or signifcantly improved in all afflicted. Therapy overall was well tolerated with the majority of toxicities being transient. Neuropathy (grade 1; n=3; grade 2; n=1) and hyperglycemia (grade 2; n=1) were minimal. The only greater or equal to grade 3 toxicities were (grade 3: elevated bilirubin, infection, and blurred vision; grade 4: anemia). Follow-up bone marrow examination, when available, did not show post-treatment histological changes.CONCLUSIONS: This phase II study of combination therapy with thalidomide-prednisone-etanercept in patients with MMM confirms the previously recognized value of etanercept in alleviating constitutional symptoms. However, the PET regimen does not appear to be superior to thalidomide-prednisone combination in terms of therapeutic value for anemia, thrombocytopenia, or splenomegaly.

An unusual presenting feature of precursor T-cell acute lymphoblastic leukemia/lymphoma

Precursor T-acute lymphoblastic leukemia/lymphoma (ALL) comprises approximately 20–25% of adult cases of ALL. Precursor T-ALL tends to present in adolescent males as lymphomas and is characteristically presented with a high leukocyte count or large mediastinal mass at initial presentation. We report here a rare manifestation of precursor T-ALL presenting with clinically significant involvement of ovary and spine at initial presentation. A 33-year-old woman presented with low abdominal pain and lumbago for 1 day in July 2004. Physical examination revealed tenderness in the right lower abdominal region. No enlarged spleen, liver or lymph nodes was palpable. Hematologic data showed Hb level of 8.3 g/dl, 8.91×10/l of WBC with 87% of segmented neutrophils, 10% of lymphocytes, 3% of monocytes, and 328×10/l of platelets. An ultrasound examination of the pelvis revealed a cystic mass with a dimension of 6.5×4.5 cm in the right ovary. An emergent operation was performed for presumed symptomatic ovarian cyst. Ovarian masses were solid masses rather than cystic masses under the laparotomy, and right salpingooophorectomy with left ovary wedge resection was done. Histologic examination of the ovarian masses revealed lymphoblastic infiltration (Fig. 1a). They showed positive immunoreactivity for CD3 (cytoplasmic pattern), CD10 and CD45 (leukocyte common antigen) and negative immunoreactivity for CD20, CD30, CD117 and CD68. On the fourth postoperative day the patient developed abrupt-onset paraplegia and sensory loss of both lower extremities. Magnetic resonance imaging of the spine showed a dorsal epidural mass destroying from T9 to T12, and multiple enhancing lesions in L3, L4, S1 vertebral body were revealed (Fig. 1b). Emergency operative decompression of the spinal cord was done to relieve the lower extremity paraplegia. Autogenous iliac bone graft and from T7 to T12 posterolateral fusion following T9, 10, 11 total and T8 partial decompressive laminectomy was done after the removal of epidural mass. Histologic examination of the spinal mass revealed lymphoblastic and eosinophilic infiltration (Fig. 1c). The lymphoblasts were characterized by positive immunoreactivity for CD3 (cytoplasmic pattern), CD10 and CD45 (leukocyte common antigen) and negative immunoreactivity for CD20, CD30, CD117 and CD68. Under the impression of T lymphoblastic lymphoma, bone marrow examination was done. The bone marrow touch imprint preparation showed that 92% of marrow cells were lymphoblasts. They were variable in size and characterized by high nuclear–cytoplasmic ratio (Fig. 1d). Trephine biopsy showed diffuse infiltration of marrow by lymphoblasts, which revealed numerous mitotic figures (Fig. 1e). Immunohistochemical stain showed positive reactivity for CD3 (cytoplasmic pattern) and negative for CD20 (Fig. 1f). Chromosomal analysis of bone marrow demonstrated a 46XX karyotype in 100% (20/20) of the cells. A CT scan of the chest demonstrated an anterior mediastinal mass approximately 12×8 cm. A diagnosis of precursor T-ALL was made. The patient was started on induction chemotherapy with vincristine, prednisone, daunorubicin and L-asparaginase (VPDL). The anterior mediastinal mass regressed substantially and revealed a focal streaky density on followup chest CT checked on 28 June 2004. In August 2004, remission was successfully achieved as shown by follow-up bone marrow examination. The patient subsequently received further consolidation VPDL therapy and currently remains in good health. Precursor T-ALL is associated with numerous unfavorable presenting features; thus, patients have a worse prognosis than patients with precursor B-ALL. In adults, higher white blood cell counts (>30,000/μl) and older age (>60 years) shorten durations of remissions and overall survival M.-A. Kim (*) . K.-Y. Maeng Department of Laboratory Medicine, Gyeongsang National University Hospital, 90 Chilam-Dong, Jinju, 660-702, South Korea e-mail: givmea2004@yahoo.co.kr Tel.: +82-55-7508639 Fax: +82-55-7622696

Generalized neutrophilic dermatosis: A rare presentation of myelodysplastic syndrome

We present a 30-year-old man admitted with generalized cutaneous lesions, fever and cough. Examination of skin biopsies of a papular lesion revealed dense neutrophilic infiltration of the upper dermis, so these lesions were diagnosed as neutrophilic dermatosis. Peripheral blood examination and bone marrow findings confirmed the diagnosis of myelodysplastic syndrome with excess blasts. The cutaneous lesions improved after administration of corticosteroid and follow-up bone marrow examination revealed a normocellular marrow. One year later he referred with acute myelogenous leukemia (AML-M0). Unfortunately, he did not respond to treatment and died a few months later due to disease progression.

Imatinib-Responsive Hypereosinophilia in a Patient with B Cell ALL

Hypereosinophilia is a rare presenting sign of acute lymphocytic leukemia. A 29-year-old male was diagnosed with idiopathic hypereosinophilic syndrome with respiratory symptoms. Although his peripheral blood eosinophilia decreased in response to treatment with imatinib mesylate, a follow-up bone marrow showed a diffuse infiltrate of myeloperoxidase-negative blasts. He was subsequently diagnosed with CD10 positive precursor B lymphoblastic leukemia. This case underscores the importance of follow-up bone marrow examination in patients who demonstrate imatinib mesylate-responsive eosinophilia.

Phase II Study of the Combination of Low-Dose Thalidomide, Prednisone, and Etanercept (“PET regimen”) in the Treatment of Anemia, Splenomegaly, and Constitutional Symptoms Associated with Myelofibrosis with Myeloid Metaplasia (MMM).

BACKGROUND: Disease manifestations in myelofibrosis with myeloid metaplasia (MMM) that require therapy include anemia, thrombocytopenia, hepatosplenomegaly, and constitutional symptoms. We have previously reported on the therapeutic value of low-dose thalidomide in combination with prednisone for the treatment of both anemia and thrombocytopenia in MMM (Blood 2003; 101:2534) and of etanercept (tumor necrosis factor-alpha antagonist) for alleviation of constitutional symptoms (Blood 2002; 99(6):2252). In the current study, we investigated the value of combining all three drugs (PET).METHODS: Study eligibility criteria included a histologically confirmed diagnosis of MMM and either severe anemia (hemoglobin < 10 g/dL) or symptomatic splenomegaly. Protocol treatment was initiated with 50 mg of oral thalidomide daily, etanercept 25 mg subcutaneously twice-a-week, and a three month prednisone taper starting at 0.5 mg/kg/day for the first month followed by a 50% reduction for the second months and a further 50% reduction for the third and final month of treatment with prednisone. Patients with a demonstrable clinical response after three months were able to remain on thalidomide and etanercept.RESULTS: To date 12 patients have been enrolled to the trial (median age 67 years, range, 54–77; 11 males). At enrollment, all patients were severely anemic (6 were red cell transfusion dependent), 6 were at least moderately thrombocytopenic (platelet count < 100 x 109//L), and 4 had severe constitutional symptoms. The responses to date included resolution of constitutional symptoms in all 4 pertinent patients, a 12–326% improvement in thrombocytopenia in 4 of 6 pertinent patients, and anemia response in 4 patients including one patient who became red cell transfusion independent. A more than 50% decrease in splenomegaly was documented in 3 patients. Only one patient experienced greater or equal to grade 3 toxicity (i.e. elevated bilirubin and infection). Follow-up bone marrow examination, when available, did not show post-treatment histological changes.CONCLUSIONS: The preliminary findings from the current ongoing phase II study of combination therapy with thalidomide-prednisone-etanercept in patients with MMM confirms the previously recognized value of etanercept in alleviating constitutional symptoms. However, at least preliminarily the PET regimen does not appear to be superior to thalidomide-prednisone combination in terms of therapeutic value for anemia, thrombocytopenia, or splenomegaly.