Jesse Jaso

Impact of induction regimen and stem cell transplantation on outcomes in double-hit lymphoma: A multicenter retrospective analysis

Patients with double-hit lymphoma (DHL), which is characterized by rearrangements of MYC and either BCL2 or BCL6, face poor prognoses. We conducted a retrospective multicenter study of the impact of baseline clinical factors, induction therapy, and stem cell transplant (SCT) on the outcomes of 311 patients with previously untreated DHL. At median follow-up of 23 months, the median progression-free survival (PFS) and overall survival (OS) rates among all patients were 10.9 and 21.9 months, respectively. Forty percent of patients remain disease-free and 49% remain alive at 2 years. Intensive induction was associated with improved PFS, but not OS, and SCT was not associated with improved OS among patients achieving first complete remission (P = .14). By multivariate analysis, advanced stage, central nervous system involvement, leukocytosis, and LDH >3 times the upper limit of normal were associated with higher risk of death. Correcting for these, intensive induction was associated with improved OS. We developed a novel risk score for DHL, which divides patients into high-, intermediate-, and low-risk groups. In conclusion, a subset of DHL patients may be cured, and some patients may benefit from intensive induction. Further investigations into the roles of SCT and novel agents are needed.

Atypical chronic myeloid leukemia is clinically distinct from unclassifiable myelodysplastic/myeloproliferative neoplasms

Atypical chronic myeloid leukemia (aCML) is a rare subtype of myelodysplastic/myeloproliferative neoplasm (MDS/MPN) largely defined morphologically. It is, unclear, however, whether aCML-associated features are distinctive enough to allow its separation from unclassifiable MDS/MPN (MDS/MPN-U). To study these 2 rare entities, 134 patient archives were collected from 7 large medical centers, of which 65 (49%) cases were further classified as aCML and the remaining 69 (51%) as MDS/MPN-U. Distinctively, aCML was associated with many adverse features and an inferior overall survival (12.4 vs 21.8 months, P = .004) and AML-free survival (11.2 vs 18.9 months, P = .003). The aCML defining features of leukocytosis and circulating myeloid precursors, but not dysgranulopoiesis, were independent negative predictors. Other factors, such as lactate dehydrogenase, circulating myeloblasts, platelets, and cytogenetics could further stratify MDS/MPN-U but not aCML patient risks. aCML appeared to have more mutated RAS (7/20 [35%] vs 4/29 [14%]) and less JAK2p.V617F (3/42 [7%] vs 10/52 [19%]), but was not statistically significant. Somatic CSF3R T618I (0/54) and CALR (0/30) mutations were not detected either in aCML or MDS/MPN-U. In conclusion, within MDS/MPN, the World Health Organization 2008 criteria for aCML identify a subgroup of patients with features clearly distinct from MDS/MPN-U. The MDS/MPN-U category is heterogeneous, and patient risk can be further stratified by a number of clinicopathological parameters.

Multi-color flow cytometric immunophenotyping for detection of minimal residual disease in AML: past, present and future

Current chemotherapeutic regimens achieve CR in a large percentage of patients withxa0 AML. However, relapse after CR remains a significant problem. The presence of leukemic cells at levels too low to be detected by conventional microscopy, termed minimal residual disease (MRD), has been associated with an increased risk of relapse and shortened survival. Detection of MRD requires the use of highly sensitive ancillary techniques. Multi-color flow cytometric immunophenotyping is a sensitive method for quick and accurate detection of MRD. Use of this method in patient management may result in lower rates of relapse and improved survival, and is an effective means of assessing novel therapeutic agents. This method can be used in the vast majority of patients with AML, regardless of the immunophenotypic, cytogenetic and molecular genetic abnormalities present. Unfortunately, conflicting data regarding optimum methods of measurement and reporting, as well as the expertize required to interpret results have limited broad application of this technique. We provide a broad overview of this technique, including its advantages and limitations, and discuss the methods employed at our institution. We also review several possible areas of future investigation.

Breast implant-associated anaplastic large cell lymphoma: sensitivity, specificity, and findings of imaging studies in 44 patients

Breast implant-associated anaplastic large cell lymphoma (BIA ALCL) is a newly described clinicopathologic entity. The purpose of this study is to describe the imaging findings of patients with BIA ALCL and determine their sensitivity and specificity in the detection of the presence of an effusion or a mass related to BIA ALCL. A retrospective search was performed of our files as well as of the world literature for patients with pathologically proven BIA ALCL who had been assessed by any imaging study including ultrasound (US), computerized tomography (CT), magnetic resonance imaging (MRI), or positron emission tomography (PET)–CT, as well as mammography. The sensitivity and specificity of each imaging modality in the detection of an effusion or a mass around breast implants was determined. We identified 44 patients who had BIA ALCL and imaging studies performed between 1997 and 2013. The sensitivity for detecting an effusion was 84, 55, 82, and 38xa0%, and for detecting a mass was 46, 50, 50, and 64xa0%, by US, CT, MRI, and PET, respectively. The sensitivity of mammography in the detection of an abnormality without distinction of effusion or mass was 73xa0%, and specificity 50xa0%. Progression-free survival was worse in patients with an implant-associated mass (pxa0=xa00.001). Conclusions: Current imaging with US, CT, MR, and PET appears suboptimal in the detection of an imaging abnormality associated with BIA ALCL. This under diagnosis may reflect a lack of awareness of this rare entity suggesting the need for better understanding of the spectrum of imaging findings associated with BIA ALCL by breast imagers.

Prognostic significance of immunophenotypic and karyotypic features of Philadelphia positive B-lymphoblastic leukemia in the era of tyrosine kinase inhibitors

Philadelphia chromosome (Ph)‐positive B‐lymphoblastic leukemia exhibits immunophenotypic, karyotypic, and molecular genetic heterogeneity. The prognostic significance of these parameters was assessed in the context of intensive tyrosine kinase inhibitor (TKI)‐based chemotherapy.

CD5-positive mucosa-associated lymphoid tissue (MALT) lymphoma: a clinicopathologic study of 14 cases

Extranodal marginal zone lymphoma of mucosa-associated lymphoid tissue (MALT lymphoma) is a B-cell neoplasm that is typically CD5 negative. We describe the clinicopathologic, immunophenotypic, and cytogenetic features of 14 cases of CD5+ MALT lymphoma. There were 9 men and 5 women (median age, 68 years; range, 34-87 years). MALT lymphoma was initially diagnosed in salivary glands (n = 4), nasopharynx (n = 2), and 1 case each in conjunctiva, thyroid, stomach, colon, skin, lung, kidney, and retroperitoneum. Two patients had localized disease; 9 had disseminated disease with generalized lymphadenopathy (n = 8), multifocal lymphoma (n = 6), or bone marrow involvement (n = 5). No staging information was available for the remaining patients. None presented with B symptoms, splenomegaly, cytopenias, lymphocytosis, monoclonal gammopathy, or elevated serum lactate dehyrogenase. Serum β2-microglobulin was elevated in 6. Morphologically, the neoplasms had features typical of MALT lymphoma being composed of small- to medium-sized cells with round to slightly irregular nuclear contours and moderate amount of cytoplasm. Lymphoepithelial lesions were noted in 4 cases. CD5 was positive in all cases by immunohistochemistry (n = 12) and/or flow cytometry (n = 11). All cases assessed were negative for cyclin D1 (13/13) and CD10 (11/11). Conventional cytogenetics in 7 cases showed trisomy 3 in 3 and diploid in 4. With a median follow-up of 71 months (range, 2-131 months), overall survival at 5 years was 100%, although 5 patients required chemotherapy. Our results show that CD5 expression is rare in MALT lymphoma, and is often associated with nongastric disease and an increased tendency to present with disseminated disease. Overall survival is excellent with appropriate therapy.

Impact of oncogene rearrangement patterns on outcomes in patients with double-hit non-Hodgkin lymphoma

Double‐hit lymphomas (DHLs) are collectively defined as B‐cell non‐Hodgkin lymphomas harboring rearrangements of MYC as well as B‐cell lymphoma 2 (BCL2) and/or B‐cell lymphoma 6 (BCL6). To the authors knowledge, the impact of specific oncogene rearrangements on outcomes of patients with DHL who are treated with immunochemotherapy has not been previously described.

Bone marrow fibrosis in patients with primary myelodysplastic syndromes has prognostic value using current therapies and new risk stratification systems

Bone marrow fibrosis has recently been recognized as an adverse histological feature in patients with primary myelodysplastic syndromes. In this study, we assessed the prognostic impact of bone marrow fibrosis in patients with primary myelodysplastic syndromes under the recently revised new risk stratification systems: the New Comprehensive Cytogenetic Scoring System and the Revised International Prognostic Scoring System. From 2002 to 2012, a total of 79 (13%) patients with primary myelodysplastic syndromes and moderate/severe bone marrow fibrosis were identified; and these patients were compared with a control group of 166 patients with myelodysplastic syndromes but no significant fibrosis. Bone marrow fibrosis predicted an inferior overall survival and leukemia event-free survival for patients who received no hematopoietic stem cell transplant in univariate and multivariate analysis. Eleven patients with bone marrow fibrosis and 32 control group patients underwent hematopoietic stem cell transplant; and bone marrow fibrosis was an independent risk for an inferior overall survival but not leukemia-free survival. In addition, 17 (4%) patients developed bone marrow fibrosis during the course of myelodysplastic syndromes, which was accompanied by clinical and cytogenetic evidence of disease progression. JAK2 V617F mutations were detected in 6 of the 28 patients with bone marrow fibrosis presenting at the time of diagnosis and 2 of the 7 patients with bone marrow fibrosis developing in the course of disease, significantly higher than the control group patients. We conclude that bone marrow fibrosis is an adverse risk feature in primary myelodysplastic syndromes in the current therapeutic era, and this risk feature is not captured by newly revised risk stratification systems. Inclusion of bone marrow fibrosis in patient assessment may further aid in risk-adapted therapeutic decisions.

Clinicopathologic Features of CD5-Positive Nodal Marginal Zone Lymphoma

OBJECTIVESnTo describe the clinicopathologic findings of seven patients with CD5-positive nodal marginal zone lymphoma (NMZL).nnnMETHODSnWe searched cases of NMZL over a 10-year interval and identified seven cases of CD5-positive NMZL. The clinical, histologic, and immunophenotypic findings of this group were reviewed, and the frequency of dissemination in this group was compared with that of 66 patients with CD5-negative NMZL.nnnRESULTSnOther than CD5 expression, the histologic and immunophenotypic findings were typical of NMZL. Six (86%) of seven patients had lymphadenopathy above and below the diaphragm, and all six patients assessed had bone marrow involvement. In the CD5-negative group, 28 (42%) patients had lymphadenopathy above and below the diaphragm, and 36 (55%) had bone marrow involvement (P = .045 and P = .037, respectively). Six of seven patients were alive at last follow-up, with a median follow-up of 32 months (3-154 months).nnnCONCLUSIONSnCD5 expression in NMZL correlates with a higher frequency of dissemination, but patients have an indolent clinical course and excellent overall survival.

Impact of induction regimen and stem cell transplantation on outcomes in patients with double hit lymphoma: a large multicenter retrospective analysis

Patients with double-hit lymphoma (DHL), which is characterized by rearrangements of MYC and either BCL2 or BCL6, face poor prognoses. We conducted a retrospective multicenter study of the impact of baseline clinical factors, induction therapy, and stem cell transplant (SCT) on the outcomes of 311 patients with previously untreated DHL. At median follow-up of 23 months, the median progression-free survival (PFS) and overall survival (OS) rates among all patients were 10.9 and 21.9 months, respectively. Forty percent of patients remain disease-free and 49% remain alive at 2 years. Intensive induction was associated with improved PFS, but not OS, and SCT was not associated with improved OS among patients achieving first complete remission (P = .14). By multivariate analysis, advanced stage, central nervous system involvement, leukocytosis, and LDH >3 times the upper limit of normal were associated with higher risk of death. Correcting for these, intensive induction was associated with improved OS. We developed a novel risk score for DHL, which divides patients into high-, intermediate-, and low-risk groups. In conclusion, a subset of DHL patients may be cured, and some patients may benefit from intensive induction. Further investigations into the roles of SCT and novel agents are needed.