Transient stress lymphocytosis (TSL) is an under-recognized phenomenon associated with an acute stressful event such as physical trauma or various emergency medical conditions. Lymphocytosis generally resolves within several hours to days of the stressor. While most reports of TSL predominantly involve adult patients, it has only rarely been reported in pediatric patients. Here, we describe the clinical course of a 9-year-old male who developed TSL following a traumatic fall from a second-story balcony and provide a systematic literature review of TSL.

Lymphoid aggregates are found in a minority of bone marrow biopsy and aspirate specimens, and when present, the distinction between benign and malignant aggregates can represent a diagnostic challenge. Morphologic and immunophenotypic evaluation of the aggregates can aid in that distinction but in a few cases, detection of immunoglobulin heavy chain (IGH) and kappa light chain (IGK) gene rearrangements may be needed to rule in or out a malignant disease process. We studied the role of testing for IGH/IGK rearrangements in the distinction between benign and malignant B cell-predominant lymphoid aggregates. Only a few studies have addressed this issue and most lacked an adequate number of cases for establishing statistical significance. Our study retrospectively evaluated 120 bone marrow aspirate and biopsy specimens, 79 cases originally diagnosed with benign lymphoid aggregates [4,5], and 41 demonstrating a B-cell lymphoma with malignant aggregates. Immunohistochemical stains were performed on all cases in our study and flow cytometry results were available in the vast majority of cases (98%). All patients included in our study but 9 had at least 2 years of clinical follow-up information. Of the malignant lymphoma cases, IGH/IGK rearrangements were demonstrated by polymerase chain reaction in 60% of the cases. Moreover, clonal rearrangements were identified in 15% of the cases with benign aggregates. After at least 2 years of follow-up, only one case with a positive clonality study occurring in the setting of morphologically benign-appearing bone marrow lymphoid aggregates experienced a relapse of non-Hodgkin lymphoma. Molecular analysis of the IGH and IGK genes may have utility in confirming the presence of malignancy in bone marrow aspirates and biopsy specimens. False-negative results, however, are possible due to testing limitations and sampling issues. Moreover, patients with conditions such as autoimmune disorders or infectious diseases are shown to also develop clonal B-cell lymphoid aggregates. As a result, we recommend a thorough morphological examination, informative immunohistochemical staining, accurate flow cytometric analysis, and current IGH/IGK rearrangement testing when evaluating bone marrow specimens containing B cell-predominant lymphoid aggregates, with the knowledge that molecular clonality results should be carefully interpreted in the context of morphological and immunophenotypic findings to prevent misdiagnosis.

Development of post-chemotherapy histiocyte-rich pseudotumor (PHP) is an underrecognized event following therapy in lymphoma patients and may mimic residual tumor using current therapy monitoring protocols. We report a series of 5 patients with PHP along with a review of the literature. In our series, we describe 3 patients with persistent hypermetabolic masses by positron emission tomography-computed tomography, one with persistent terminal ileal nodules on endoscopy, and one with bone marrow involvement, a site not associated with mass-like disease. Twenty-three patients with long-term follow-up were identified from our series and review of the literature. Forty-four percent of patients received additional therapy, and only 4% of patients died of lymphoma. This study illustrates that PHPs are not identified using current lymphoma therapy monitoring algorithms and may result in overtreatment with risk for additional therapy-related complications. The need for confirmatory tissue biopsy in this setting is recommended.

Kikuchi-Fujimoto disease is a self-limited disease of unknown etiology that is clinically defined by fevers accompanied by tender posterior cervical lymphadenopathy. It often presents acutely or sub-acutely, and due to its non-specific features, the differential diagnosis is broad and includes infectious, autoimmune, and malignant causes. Although cases of extra-cervical disease are not uncommon, involvement of retroperitoneal lymph nodes has only rarely been reported. Here, we describe a patient with Kikuchi-Fujimoto disease who presented with fever of unknown origin, abdominal pain, and enlarged hypermetabolic retroperitoneal lymph nodes.

Incidence trends in acute lymphoblastic leukemia (ALL) demonstrate disparities by race and ethnicity. We used data from the Surveillance, Epidemiology, and End Results Registry to evaluate patterns in ALL incidence from 2000 to 2016, including the association between percentage of people born in a foreign country at the county level and ALL incidence. Among 23,829 persons of all ages diagnosed with ALL, 8,297 (34.8%) were Latinos, 11,714 (49.2%) were non-Latino (NL) Whites, and 1,639 (6.9%) were NL Blacks. Latinos had the largest increase in the age-adjusted incidence rate (AAIR) of ALL during this period compared with other races/ethnicities for both children and adults: The AAIR was 1.6 times higher for Latinos (AAIR = 2.43, 95% confidence interval (CI): 2.37, 2.49) than for NL Whites (AAIR = 1.56, 95% CI: 1.53, 1.59) (P < 0.01). The AAIR for all subjects increased approximately 1% per year from 2000 to 2016 (annual percent change = 0.97, 95% CI: 0.67, 1.27), with the highest increase being observed in Latinos (annual percent change = 1.18, 95% CI: 0.76, 1.60). In multivariable models evaluating the contribution of percentage of county residents who were foreign-born to ALL risk, a positive association was found for percentage foreign-born for NL Whites (P for trend < 0.01) and NL Blacks (P for trend < 0.01), but the reverse was found for Latinos (P for trend < 0.01); this is consistent with tenets of the "Hispanic paradox," in which better health outcomes exist for foreign-born Latinos.

Background: Prodromal/pre-leukemic acute leukemia is rare, mostly described in childhood B-lymphoblastic leukemia (B-ALL), with its initial presentation confused with aplastic anemia (AA). Findings reported in pediatric prodromal/pre-leukemic B-ALL include female preponderance, bone marrow (BM) fibrosis and uniform hypocellularity, and transient recovery. Reports in adults are rarer still. We conducted a retrospective review of adult patients we diagnosed with B-ALL and mixed phenotype acute leukemia with B-lymphoid and myeloid components (MPAL-B/myeloid) with prodromal/pre-leukemic manifestations. We sought to identify common clinical features, peripheral blood (PB) and BM morphology, diagnostic considerations, and clinical follow-up (whenever available) to aid in improved recognition in the adult setting. Methods: Patients with unusual presentations preceding overt acute leukemia were identified from pathology and clinical records from our institution from 2010-2020. These include (a) incidental PB blasts and partial BM-based disease, followed by spontaneous, transient regression (STR); (b) pancytopenia with rare to absent PB blasts and unexpected detection of BM-based blasts (10% or lower), compatible with aleukemic prodrome (AP) cases; (c) pancytopenia without PB blasts yet unexpected excess BM-based blasts (50% or greater) followed by marked reduction of BM-based blasts (compared to initial BM) despite absence of treatment (AP-->SR). BM pathology during prodromal/pre-leukemic phases were reviewed to identify key morphologic features. Results: Seven patients were identified (4 M, 3 F; age range 20-75 years), including one previously described by our group (Table 1). All were of Hispanic ethnicity. They displayed a broad range of symptoms including fatigue, fevers, throat pain, and weight loss. Initial presentations were STR in 3, AP in 2, and AP-->SR in 2. Although variably cellular, all BM trephine biopsies in prodromal/pre-leukemic phase had at least focal hypocellularity with stromal damage, characterized by granular to fibrillary stroma, striking cellular dropout, and multiloculated fat cells with fibrinoid appearance. Relative erythroid hyperplasia was seen in 4, while dyserythropoiesis and dysmegakaryocytopoiesis were both observed in 2 cases, raising concern for myelodysplastic syndrome (MDS). AA and MDS were, in some cases, seriously considered in the initial differential diagnosis. Because of low level BM blasts at initial presentation in most (5/7), definitive lineage designation was sometimes challenging. Furthermore, flow cytometric data was limited and IHC stained only a sparse number of immature B-cells; thus normal precursor B-cell (hematogone) hyperplasia was a strong possibility. Workup in 2 cases during low numbers of BM-based blasts or spontaneous blast reduction (cases #6 and #7, respectively) revealed T-cell clones on PCR/NGS testing. In STR and AP cases, the disease proceeded from initial presentation to overt leukemia within a fairly short interval (range 1.5 - 7.0 months; median 2.5). Final diagnosis in the majority of cases (6/7) was B-ALL, with one case of MPAL-B/myeloid. Conclusion: Herein we describe a series of 7 adult prodromal/pre-leukemic cases of B-lymphoblasts (6 B-ALL; 1 MPAL-B/myeloid) with a variety of clinical presentations. In contrast to the female-predominant pediatric prodromal B-ALLs, most of our adult cases occurred in males. Given pancytopenia, relatively low numbers, and difficulty in assigning blast lineage, diagnostic considerations initially included MDS, AA, and hematogone hyperplasia with marrow regeneration. Key morphologic features that favored a prodromal/pre-leukemic case of B-lymphoblasts over MDS or AA were profound stromal damage and expansion (albeit low numbers) of immature B-cells - findings that would be unusual in low-grade MDS and AA. Intriguingly, in 2 of our cases, T-cell clones detected on PCR testing during low blast levels may indicate an immunologic role of T-cells in transiently reducing blasts in prodromal acute leukemia, as previously suggested by Zimmermannova and colleagues (Haematol2017;102:e225-228). Regardless of whether patients experienced STR, AP, or AP-->SR, close clinical follow-up is advised, as progression to overt leukemia occurs within a relatively short time frame (median of 2.5 months in our series). Disclosures No relevant conflicts of interest to declare.

A 23-year-old male with HIV/AIDS was admitted with worsening dyspnea and cough, high fevers, and anasarca. Imaging studies revealed diffuse interstitial infiltrates and hepatosplenomegaly. Pertinent laboratory values demonstrated elevated levels of ferritin (6039 ng/mL) and triglycerides (264 mg/dL), pancytopenia (absolute neutrophil count <0.1 × 10/L; hemoglobin 5.5 g/dL; platelets [PLTs] 19 × 10/L with reticulocytopenia, elevated fibrinogen (779 mg/dL), elevated D-dimer (2.73 μg/mL FEU), and mildly elevated PT/PTT (17 and 38.5 sec). Of note, PLT counts were refractory to the majority of 74 PLT transfusions, with an average corrected count increment (CCI) of 2607 × 10 cells/L. He also had multiple negative PLT crossmatches, thus eliminating alloimmunization to human leukocyte or human PLT antigens. Marrow aspiration revealed hemophagocytes with intracytoplasmic RBCs and multiple nucleated cells (such as plasma cells, see figure, left) as well as ingested PLTs (i.e., thrombophagocytosis, see figure). Extensive workup for other infectious, autoimmune, and malignant etiologies was negative. He was diagnosed with hemophagocytic syndrome/hemophagocytic lymphohistiocytosis (HLH), supported by the presence of fevers, pancytopenia, hyperferritinemia, hypertriglyceridemia, and cytomorphology compatible with HLH. These findings translated into an HScore of 257, correlating with a greater than 99% probability of HLH. Thrombocytopenia in HLH patients is most commonly attributed to disseminated intravascular coagulation or is multifactorial. However, prominent marrow thrombophagocytosis (reported rarely in the literature) leads us to hypothesize that this may have also contributed to this patient's persistent thrombocytopenia and PLT refractoriness. The patient was unable to tolerate treatment as his condition rapidly deteriorated, leading to his expiration. Received: 29 April 2020 Revised: 10 June 2020 Accepted: 14 June 2020

Abstract Objectives. The causes of ALL are determined in part by genetic factors but less clear is the role of the environment. Temporal and demographic changes in incidence may help illuminate causes and help direct new lines of research. We sought to investigate in the US from 2000-2016, 1) the distribution of ALL incidence by race/ethnicity, 2) trend change in ALL incidence and 3) the association between ALL incidence and location of birth (US or a foreign country) among different ages and race/ethnicity groups. Methods. We used data from the population-based Surveillance, Epidemiology and End Results (SEER) Registry. Age-adjusted incidence rates (AAIRs) per 100,000 persons were calculated for people of Latino ethnicity (all races), Non-Latino (NL) White, NL Black, NL Asian and Pacific Islander (API), NL American Indian, and Alaskan Native (AIAN). Trends of ALL from 2000 to 2016 were evaluated with the annual percent change (APC) of AAIRs. We further used a Poisson regression model with standardized population offset to analyze the association between the community-level percent of people born in a foreign country and the AAIR of ALL among NL Whites, NL Blacks, and Latinos. The analyses were stratified by race/ethnicity and age groups, and adjusted for sex, year of diagnosis and socioeconomic position (SEP, identified with a time-dependent Yost index variable from census tract). Results. Among 23,829 individuals of all ages diagnosed with ALL from 2000 to 2016 in the US, 8,297 were Latinos, 11,714 were NL Whites, and 1,639 were non-Latino Blacks. Compared to NL Whites (AAIR=1.56), the AAIR was significantly higher for Latinos (AAIR=2.43; p<.001) but lower for NL Blacks (AAIR=0.95; p<.001). The AAIR increased significantly from 2000-2016 overall (APC=0.97; 95% CI:0.67, 1.27), with the highest increase in Latinos (APC=1.18; 95% CI: 0.76, 1.60). The AAIR for NL Whites, APIs, and AIANs remained stable during the study period. In adjusted models, AAIRs increased significantly with the percent of foreign-born for NL Whites (p-trend<.001) and Blacks (p-trend<.001), but decreased with the percent of foreign-born for Latinos (p-trend<.001). This finding was consistent for all age groups. Conclusion. The Age Adjusted Incidence Rates (AAIRs) of ALL from 2000-2016 were highest among Latinos compared to other ethnic groups. Latinos had the fastest increase in AAIR in this period, which was significant in the childhood, young adult, and older adult age groups. Our analysis showed several intriguing trends relating to ethnicity and country of origin which remain unexplained in the scientific literature. Most notably, we show that previously-noted increases in the incidence of ALL for Latinos have continued to climb, in both children and adults, establishing this group as the most highly burdened with this disease. These trends should help direct future research into risk identification and disease prevention in the most vulnerable populations. Citation Format: Qianxi Feng, Maria Vergara-Lluri, Ivo Muskens, Roberta McKean-Cowdin, Scott Kogan, Russell Brynes, Adam de Smith, Joseph Wiemels. Trends in acute lymphocytic leukemia (ALL) incidence in the US from 2000-2016 [abstract]. In: Proceedings of the Twelfth AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2019 Sep 20-23; San Francisco, CA. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2020;29(6 Suppl_2):Abstract nr A105.

Supplemental Digital Content is available in the text.

Objectives: To assess bone marrow (BM) sampling in academic medical centers. Methods: Data from 6,374 BM samples obtained in 32 centers in 2001 and 2011, including core length (CL), were analyzed. Results: BM included a biopsy (BMB; 93%) specimen, aspirate (BMA; 92%) specimen, or both (83%). The median (SD) CL was 12 (8.5) mm, and evaluable marrow was 9 (7.6) mm. Tissue contraction due to processing was 15%. BMB specimens were longer in adults younger than 60 years men, and bilateral, staging, and baseline samples. Only 4% of BMB and 2% of BMB/BMA samples were deemed inadequate for diagnosis. BM for plasma cell dyscrasias nonphysician operators, and ancillary studies usage increased while bilateral sampling decreased over the decade. BM-related quality assurance programs are infrequent. Conclusions: CL is shorter than recommended and varies with patient age and sex, clinical circumstances and center experience While pathologists render diagnoses on most cases irrespective of CL, BMB yield improvement is desirable.

Background: ITP, characterized by isolated platelet reduction, is classified as persistent within 3-<12 months (mo) of diagnosis and chronic (cITP) when it continues for ≥12 mo. Theoral thrombopoietin-receptor agonist (TPO-RA), EPAG, is approved for the treatment of previously treated (eg corticosteroids, immunoglobulins) cITP patients (pts). Very few analyses have evaluated EPAG treatment specifically in subgroups of persistent ITP pts. To gain better insight into EPAG effects on platelet counts, and long-term safety, in persistent ITP, a subanalysis of a Phase IV, open-label safety study of EPAG in adults with persistent/cITP (Brynes et al. Acta Haematol 2017;137:66-72) was performed.

Background: Autoimmune myelofibrosis (AIMF) is an underrecognized cause of nonmalignant bone marrow fibrosis which occurs in the presence or absence of a defined systemic autoimmune disease. Patients with AIMF present with cytopenias and autoantibodies, and have a distinctive nonclonal myelofibrosis on bone marrow examination. AIMF is distinguished from primary myelofibrosis by the absence of splenomegaly, eosinophilia, or basophilia, and the absence of abnormal myeloid, erythroid, or megakaryocytic morphology. Objectives: The objective of the study was to describe the clinical presentation and outcomes of patients with AIMF. Methods: We conducted a single-institution, retrospective chart review of patients diagnosed with AIMF to investigate clinical presentations, therapies, and outcomes. Results: Twelve patients with AIMF were identified with a mean follow-up of 5.8 years. All patients had detectable autoantibodies and the majority had concomitant autoimmune disorders. Four patients experienced a complete response of cytopenias and 3 patients experienced a partial response (PR) of cytopenias with immunosuppressive therapy. One patient achieved a PR following splenectomy. No patients were diagnosed with myeloproliferative neoplasms during the follow-up period. Conclusions: AIMF contributes to cytopenias in the subset of patients with various autoimmune disorders. The majority of patients with AIMF experience an improvement in cytopenias with immunosuppressive therapy.

IntroductionEvaluation of cellularity is an essential component of bone marrow trephine biopsy examination. The standard practice is to report the results as visual estimates (VE). Digital image analysis (DIA) offers the promise of more objective measurements of cellularity. MethodsAdult bone marrow trephine biopsy sections were assessed for cellularity by VE. Sections were scanned using an Aperio AT2 Scanscope and analyzed using a Cytonuclear (version 1.4) algorithm on halo software. Intraclass correlation (ICC) was used to assess relatedness between VE and DIA, and between MRI and DIA for a separate subset of patients. Trephine biopsy sections from a subset of patients with bone marrow biopsies uninvolved by malignancy were assessed for age-related changes. ResultsInterobserver VE agreement was good to excellent. The ICC value was 0.81 for VE and DIA, and 0.50 for MRI and DIA. Linearity studies showed no statistically significant trend for age-related changes in cellularity in our cohort (r=-.29, P=.06). ConclusionsAgreement was good between VE and DIA. It may be possible to use DIA or VE to measure cellularity in the appropriate clinical scenario. The limited sample size precludes similar determinations for MRI calculations. Further studies examining healthy donors are necessary before making definitive conclusions regarding age and cellularity.

Extra-osseous masses are rarely seen in Gaucher disease. Here we present a case of a 30-year-old patient with Gaucher disease type 3, receiving β-glucocerebrosidase enzyme replacement therapy, who presented with slowly enlarging masses along her back. There was no osseous extension seen on imaging. Biopsy of the mass ultimately showed extensive soft tissue infiltration by Gaucher cells. No other cases of soft-tissue masses of this extent have been described in the literature, and therefore management remains unclear.

BACKGROUND:The long-term effects of eltrombopag on bone marrow (BM) reticulin and/or collagen deposition in previously treated adults with chronic immune thrombocytopenia (ITP) were assessed.METHODS:Three BM biopsies were collected at baseline and after 1 and 2 years of eltrombopag treatment. Specimens were centrally processed, stained for reticulin and collagen, independently reviewed by 2 hematopathologists, and rated according to the European Consensus 0-3 scale of marrow fibrosis (MF).RESULTS:Of 162 patients enrolled, 93 completed all 3 protocol-specified BM biopsies. All patients with a baseline assessment were negative for collagen. Of 159 patients assessed at baseline, 150 (94%) had normal reticulin (MF-0) and 9 (6%) had minimally increased reticulin (MF-1). After 2 years, 83/93 patients (89%) with BM biopsies had MF-0, 10 (11%) had MF-1, and none had MF-2 or MF-3. Five out of 127 patients (4%) at 1 year and 1 out of 93 (1%) at 2 years had collagen deposition. None of the patients had clinical symptoms typical of BM dysfunction or abnormalities of clinical concern based on white blood cell count or peripheral blood smear.CONCLUSION:For most patients with chronic ITP, eltrombopag is not associated with clinically relevant increases in BM reticulin or collagen formation.

Patients with chronic myelogenous leukemia (CML) present typically with an elevated white blood cell count (WBC) and cytogenetic or molecular genetic evidence of t(9;22)/BCR-ABL1 fusion gene. Rarely, CML patients may present with a normal or mildly elevated WBC and are asymptomatic, and we describe 7 patients in this study. The WBC in these patients ranged from 3.6 to 14.3 K/mm(3) with 50% to 73% granulocytes and 0% blasts. In all patients, t(9;22)(q34;q11.2) was detected by conventional cytogenetics, and BCR-ABL1 fusion was shown, supporting the diagnosis of preleukemic CML (pre-CML). We compared these patients with a group of 5 cases of CML in chronic phase (CML-CP) and 5 bone marrow specimens with a leukemoid reaction (n=5). Reticulin, CD34, and CD61 immunostains were performed on all bone marrow biopsy specimens. Peripheral blood absolute basophilia (≥200/mm(3)) was noted in only 4 of 7 pre-CML cases, whereas it was present in all CML-CP cases and absent in leukemoid reaction cases. The mean ±SD of microvascular density of pre-CML cases (10.0 ± 4.3 vessels/200× field) was twice that of leukemoid reaction cases (5.0 ± 1.0) (P=.02; Student t test) but similar to that of CML-CP cases (12.5 ± 3.6). Microvessels in pre-CML, highlighted by CD34, were tortuous with abnormal branching, although to a lesser extent than those found in CML-CP. Microvessels in leukemoid reaction were generally straight. The percentage of small, hypolobated megakaryocytes, highlighted by CD61 in pre-CML, was 40%, 3 times that found in leukemoid reaction cases (13%) but less than that of CML-CP cases (86%). We conclude that pre-CML should be suspected in patients with a normal to mildly elevated WBC and absolute basophilia. Bone marrow examination can usually distinguish pre-CML from a leukemoid reaction based on the percentage of small, hypolobated megakaryocytes; microvascular density; and morphologic features.

A predominantly diffuse growth pattern and CD23 co-expression are uncommon findings in nodal follicular lymphoma and can create diagnostic challenges. A single case series in 2009 (Katzenberger et al) proposed a unique morphologic variant of nodal follicular lymphoma, characterized by a predominantly diffuse architecture, lack of the t(14;18) IGH/BCL2 translocation, presence of 1p36 deletion, frequent inguinal lymph node involvement, CD23 co-expression, and low clinical stage. Other studies on CD23+ follicular lymphoma, while associating inguinal location, have not specifically described this architecture. In addition, no follow-up studies have correlated the histopathologic and cytogenetic/molecular features of these cases, and they remain a diagnostic problem. We identified 11 cases of diffuse, CD23+ follicular lymphoma with histopathologic features similar to those described by Katzenberger et al. Along with pertinent clinical information, we detail their histopathology, IGH/BCL2 translocation status, lymphoma-associated chromosomal gains/losses, and assessment of mutations in 220 lymphoma-associated genes by massively parallel sequencing. All cases showed a diffuse growth pattern around well- to ill-defined residual germinal centers, uniform CD23 expression, mixed centrocytic/centroblastic cytology, and expression of at least one germinal center marker. Ten of 11 involved inguinal lymph nodes, 5 solely. By fluorescence in situ hybridization analysis, the vast majority lacked IGH/BCL2 translocation (9/11). Deletion of 1p36 was observed in five cases and included TNFRSF14. Of the six cases lacking 1p36 deletion, TNFRSF14 mutations were identified in three, highlighting the strong association of 1p36/TNFRSF14 abnormalities with this follicular lymphoma variant. In addition, 9 of the 11 cases tested (82%) had STAT6 mutations and nuclear P-STAT6 expression was detectable in the mutated cases by immunohistochemistry. The proportion of STAT6 mutations is higher than recently reported in conventional follicular lymphoma (11%). These findings lend support for a clinicopathologic variant of t(14;18) negative nodal follicular lymphoma and suggests importance of the interleukin (IL)-4/JAK/STAT6 pathway in this variant.

Pegylated interferon α-2a (Peg-IFN) has been shown to induce hematologic and molecular responses in patients with the Philadelphia-negative myeloproliferative neoplasms (MPNs), including polycythemia vera (PV) and essential thrombocythemia (ET). We describe a series of patients with long-standing MPNs among whom Peg-IFN was initiated when they developed anemia and increased bone marrow reticulin fibrosis suggestive of early transformation to post-ET (PET) or post-PV (PPV) myelofibrosis (MF). Six patients were treated with Peg-IFN for a mean duration of 33.8 months (range 2–63 months). Five patients had long-standing ET (three were calreticulin (CALR)-positive, one janus kinase 2 (JAK2)-positive, and one JAK2-negative and CALR-negative), and one had long-standing JAK2-positive PV prior to starting Peg-IFN. This is the first study to report that, concurrent with the improvement in anemia, serial laboratory studies demonstrate an increase in serum LDH and left-shifted myeloid cells in the peripheral circulation over approximately 6 months, followed by a gradual normalization of these findings. Splenomegaly also increased and then resolved among responding patients. Serial bone marrow biopsies were available, which showed little change except for improvement in the grade of reticulin fibrosis in two patients. Among patients with early transformation to PET or PPV MF, our data support the efficacy of Peg-IFN in improving hemoglobin levels and reducing splenomegaly. These peripheral blood findings should not, therefore, be considered evidence of treatment failure within the first year of Peg-IFN therapy.