Diana O. Treaba

The Hans algorithm is not prognostic in patients with diffuse large B-cell lymphoma treated with R-CHOP.

Our objective was to evaluate the non-germinal center (GC) profile as a marker for response and survival in DLBCL and to compare the characteristics of patients with GC and non-GC DLBCL treated with rituximab-containing regimens. In this patient-level meta-analysis, retrospective data from 712 newly diagnosed DLBCL patients treated with chemoimmunotherapy from 7 centers were analyzed. GC and non-GC profiles were defined according to the Hans algorithm. Although the non-GC profile showed a trend towards worse overall survival (HR 1.24, 95% CI 0.92-1.66; p=0.15) and progression-free survival (HR 1.29, 95% CI 0.96-1.73; p=0.09), it did not retain its value in the multivariate survival analysis. Additionally, the non-GC profile was independently associated with worse complete response rates (OR 0.55, 95% CI 0.37-0.83; p<0.01) in the multivariate logistic regression analysis. Interestingly, Asian patients had higher proportion of GC DLBCL (p=0.01).

A Novel Missense Mutation in MVK Associated With MK Deficiency and Dyserythropoietic Anemia

Mevalonate kinase deficiency (MKD) is a rare inborn error of metabolism caused by mutations in the mevalonate kinase (MVK) gene. The clinical phenotype is variable, ranging from the hyperimmunoglobulinemia D and periodic fever syndrome (HIDS) to mevalonic aciduria (MA), a severe metabolic disease. We report here for the first time (to our knowledge) the case of a patient with MKD and congenital dyserythropoietic anemia. Clinical and laboratory characteristics of inflammatory attacks were compatible with HIDS, but mild dysmorphic features and elevated urinary mevalonic acid levels in the absence of an inflammatory attack suggested an intermediate phenotype between HIDS and MA. Genomic sequencing of the MVK gene revealed compound heterozygosity for a missense mutation previously described in MA (V310M) and a novel missense mutation (Y116H). By contrast, sequencing of the novel CDAII (SEC23B) gene revealed no mutations, suggesting that the bone marrow abnormalities were causally related to the MKD. Treatment with corticosteroids and colchicine directed at controlling the autoinflammatory disease resulted in improvement of the anemia.

TAFRO Syndrome Associated with EBV and Successful Triple Therapy Treatment: Case Report and Review of the Literature

TAFRO syndrome is a rare constellation of symptoms: thrombocytopenia, anasarca, reticulin fibrosis of the bone marrow, renal dysfunction, and organomegaly. Its pathogenesis involves an excessive and inappropriate cytokine storm, most notably from IL-6, causing multiorgan failure; however, its etiology is undetermined. Starting in 2012, TAFRO syndrome was first identified in Japan as an atypical variant of Castlemans disease. Previous reports include various different treatment protocols with inconsistent survival outcomes. Here we report the first known American, EBV positive but HIV and HHV-8 negative, male with TAFRO syndrome. He was successfully treated with an unusual three-drug regimen including tocilizumab, etoposide, and rituximab. We review the literature of TAFRO syndrome, discuss its possible viral etiology, and propose an original treatment regimen.

Intracellular and extracellular rhomboid shaped crystalline inclusions in a case of IgG lambda restricted plasma cell myeloma: a case report and review of the literature

The presence of crystalline inclusions in plasma cell myeloma is a rare phenomenon and cases have been reported with rod, needle, and rectangular shaped crystals. Here, we present a case of IgG lambda restricted plasma cell myeloma with rhomboid shaped intracellular crystalline inclusions and extracellular crystal depositions in the bone marrow. Since rhomboid crystal depositions can be seen in other clinical conditions such as pseudogout, this case invites consideration of plasma cell myeloma in the differential diagnosis of patients with rhomboid crystalline deposition in the bone marrow and in sites/organs other than the bone marrow.

Primary Undifferentiated Sarcoma of the Kidney Harboring a Novel Variant of CIC-DUX4 Gene Fusion.

To the Editor: In recent issues of this journal, Yoshida et al1 reported on CIC-rearranged sarcomas, and Falzarano et al2 described renal cell carcinomas (RCCs) in patients previously treated for neuroblastoma (NB). Herein, we describe a primary renal CIC-DUX4 sarcoma, originally diagnosed as Wilms tumor (WT), in a patient previously treated for contralateral stage 4 NB. CIC-DUX4 sarcoma was retrospectively suspected after WT1 nuclear staining was reported in 95% and 70% of CIC-rearranged sarcomas.1,3 CIC-DUX4 undifferentiated sarcomas are a group of EWSR1negative primitive tumors or Ewinglike sarcomas with fusion of the human homologue of the Drosophila capicua (CIC) gene on chromosome 19 and the double-homeobox 4 (DUX4) retrogene on chromosome 4 or 10.1,3 Occasional peripheral tumors harbor variant translocation in which the CIC gene is fused with the forkhead box O4 (FOXO4) gene on the X chromosome.4 Yoshida et al1 reported that the majority of their CIC-rearranged sarcomas demonstrated nuclear immunoreactivity for WT1 protein, are positive for calretinin, and negative for NKX2.2. The vast majority of these sarcomas occur primarily in peripheral soft tissues, but visceral cases including the brain are reported.1,5,6

Spontaneous regression of chronic lymphocytic leukemia to a monoclonal B-lymphocytosis or to a normal phenotype

Abstract Spontaneous remission of chronic lymphocytic leukemia (CLL) is an unusual and poorly characterized event. We performed a search for spontaneous remission in patients with CLL. Cases must have had a pathological diagnosis of CLL with disease duration > 6 months. Spontaneous remission was defined as absence of lymphadenopathy or splenomegaly with lymphocyte counts < 5 × 109/L for > 9 months without therapy. We identified 20 cases and included one additional case from our institution. Fourteen cases (67%) showed remission into monoclonal B lymphocytosis (MBL) and seven (33%) into a normal phenotype. There was no difference in age distribution, lymphocyte count or stage between groups. There was a significant difference in the median duration of CLL prior to remission, 13 years in the MBL versus 3 years in the normal phenotype group (p = 0.03). This difference in the duration of CLL prior to remission could be due to a possible distinct pathophysiology for these events.

Low expression of Abelson interactor-1 is linked to acquired drug resistance in Bcr-Abl-induced leukemia.

The basis for persistence of leukemic stem cells in the bone marrow microenvironment remains poorly understood. We present evidence that signaling cross-talk between α4 integrin and Abelson interactor-1 (Abi-1) is involved in the acquisition of an anchorage-dependent phenotype and drug resistance in Bcr-Abl-positive leukemia cells. Comparison of Abi-1 (ABI-1) and α4 integrin (ITGA4) gene expression in relapsing Bcr-Abl-positive CD34+progenitor cells demonstrated a reduction in Abi-1 and an increase in α4 integrin mRNA in the absence of Bcr-Abl mutations. This inverse correlation between Abi-1 and α4 integrin expression, as well as linkage to elevated phospho-Akt and phospho-Erk signaling, was confirmed in imatinib mesylate -resistant leukemic cells. These results indicate that the α4-Abi-1 signaling pathway may mediate acquisition of the drug-resistant phenotype of leukemic cells.

Similar outcomes in Asian and Western patients with diffuse large B-cell lymphoma treated with R-CHOP

BACKGROUND Little is known on racial differences in patients with diffuse large B-cell lymphoma (DLBCL). The aim of this retrospective study is to compare characteristics, prognostic factors and outcomes of Asian and Western patients with DLBCL treated with rituximab, cyclophosphamide, doxorubicin, vincristine and prednisone (R-CHOP). METHODS Patient-level data was collected from 8 centers. All patients were diagnosed with DLBCL and treated with R-CHOP. Patients were divided into Asian and Western, according to the country of report. Comparisons and univariate/multivariate survival analyses were performed. RESULTS 712 patients, 455 Asian and 257 Western patients were included. Westerners were more likely to present with elevated LDH (64% vs. 48%, p<0.01) and advanced stage (58% vs. 49%, p<0.01). After a median follow-up of 36 months, there was no difference in progression-free (PFS; p=0.33) or overall survival (OS; p=0.69). There were no PFS or OS differences between races when evaluating separately each age-adjusted International Prognostic Index category. In the multivariate analyses, performance status and stage were associated with PFS and OS in both races. CONCLUSIONS There are no differences in prognostic factors, PFS and OS between Asian and Western patients with DLBCL treated with R-CHOP.

Complete Remission in Two Cases of Adult T-Cell Leukemia/Lymphoma Treated With Hyper-CVAD: A Case Report and Review of the Literature

BACKGROUND Acute T-cell leukemia/lymphoma (ATLL) is a post thymic (peripheral) T-cell neoplasm caused by human T-cell lymphotropic virus type 1 (HTLV-1). Historically, the chemotherapy regimen CHOP (cyclophosphamide/doxorubicin/vincristine/prednisone) has been the standard treatment of this rare malignancy. However, its prognosis is poor and median survival in the aggressive variants of ATLL is only 6-10 months. Recently, a more aggressive regimen piloted in Japan, vincristine/cyclophosphamide/doxorubicin/prednisone (VCAP)- doxorubicin/ranimustine/prednisone (AMP)- vindesine/etoposide/carboplatin/prednisone (VECP), has been reported to yield better survival results over biweekly CHOP in a phase III trial. However, the hyper- cyclophosphamide/vincristine/doxorubicin/dexamethasone (CVAD) regimen is a much more frequently used regimen for the treatment of aggressive hematologic malignancies, and has a higher intensity then CHOP. Yet, there is little reported experience with hyper-CVAD regimen in ATLL. CASE REPORTS We present 2 patients diagnosed with ATLL who were treated with hyper-CVAD chemotherapy and have achieved a durable complete remission. One of the patients has gone on to receive an allogeneic bone marrow transplantation and has been in complete remission for over 18 months. The other has been in a continuous remission for approximately 12 months. We also review the past published experience with the hyper-CVAD regimen in patients with ATLL. CONCLUSION A commonly used chemotherapy regimen for aggressive hematologic malignancies, hyper-CVAD, can induce durable remissions in patients with ATLL.

Spontaneous perforation of the terminal ileum in an AIDS patient on highly active antiretroviral therapy with disseminated non-tuberculous mycobacterial infection

BACKGROUND Despite the impact of highly active antiretroviral therapy (HAART), mycobacterial infections in patients with AIDS remain a frequent complication. In disseminated cases, both tuberculous and non-tuberculous mycobacterial infections may involve the gastrointestinal system and cause abdominal pain and diarrhea. While there have been cases of small bowel perforation in AIDS patients with Mycobacterium tuberculosis (MTB) infection, no case of bowel perforation in non-tuberculous mycobacterial (NTM) infection has been reported to date. CASE REPORT We report a case of spontaneous perforation of the terminal ileum in an AIDS patient with disseminated non-tuberculous mycobacterial infection who was responding to HAART. CONCLUSIONS Non-tuberculous mycobacteria can lead to spontaneous bowel perforation in patients with AIDS who are responding to HAART.