Management of post-autologous transplant relapse in patients with T-cell lymphomas.

Autologous hematopoietic cell transplantation (AHCT) is often used as a consolidation for patients with peripheral T-cell lymphomas (PTCLs) due to the poor prognosis associated with this heterogenous group of disorders. However, a significant number of patients will experience post-AHCT disease relapse. Here, we report a retrospective study of consecutive 124 patients with PTCLs who underwent AHCT from 2008 to 2020. With a median follow-up of 6.01 years following AHCT, 49 patients (40%) experienced disease relapse. As expected, more patients who were not in first complete remission experienced post-AHCT relapse. Following relapse, majority of the patients (70%) receiving systemic therapies intended as bridging to curative allogeneic HCT. However, only 18 (53%) patients eventually underwent allogeneic HCT. The estimated 3-year OS among patients proceeding to allogeneic HCT was 72% (95% CI 46%-87%). Our report details the pattern of post-AHCT relapse and the management of relapsed disease using different therapeutic modalities.

Programmed death-ligand 1 expression in patients with primary or secondary myelofibrosis.

BACKGROUND: It has been described in mice models that myeloproliferative neoplasm (MPN) with JAK2-V617F mutation has an increased expression of programmed death-ligand 1 (PD-L1) in megakaryocytes leading to cancer immune evasion by inhibiting the T-lymphocytes. AIMS: To quantify and compare the PD-L1 expression on bone marrow (BM) of patients with MPN JAK2 positive, negative, and normal controls. METHODS: We collected BM of patients with MPN JAK2 positive, negative and normal controls from 1990 to 2019. We also created a scoring system to quantify PD-L1 expression in megakaryocytes. RESULTS: We obtained 14 BM with JAK2 positive PMF, 5 JAK2 negative PMF, and 10 patients with normal BM biopsies. PD-L1 expression was higher in the JAK2 positive group compared with the control group with a score of 212.6 versus 121.1 (t-value 2.05, p-value 0.025). In addition, the score was higher in the PMF group regardless of JAK2 mutational status when compared with the control group with score of 205.9 versus 121.1 (t-value 2.12, p-value 0.021). There was no difference in the PD-L1 score between the JAK2 negative versus the control group 187.2 versus 121.1 (t-value 1.02, p-value 0.162). CONCLUSION: These findings suggest that PMF patients with a JAK2 mutation have a higher PD-L1 expression in megakaryocytes compared with the control group. We postulate that the combination of checkpoint and JAK2 inhibitors may be an active treatment option in JAK2 mutated PMF given the higher PD-L1 expression.

Five hundred years of mercury exposure and adaptation.

Mercury is added to the biosphere by anthropogenic activities raising the question of whether changes in the human chromatin, induced by mercury, in a parental generation could allow adaptation of their descendants to mercury. We review the history of Andean mining since pre-Hispanic times in Huancavelica, Peru. Despite the persistent degradation of the biosphere today, no overt signs of mercury toxicity could be discerned in present day inhabitants. However, mercury is especially toxic to the autonomic nervous system (ANS). We, therefore, tested ANS function and biologic rhythms, under the control of the ANS, in 5 Huancavelicans and examined the metal content in their hair. Mercury levels varied from none to 1.014 ppm, significantly less than accepted standards. This was confirmed by microfocused synchrotron X-ray fluorescence analysis. Biologic rhythms were abnormal and hair growth rate per year, also under ANS control, was reduced (P < 0.001). Thus, evidence of mercury's toxicity in ANS function was found without other signs of intoxication. Our findings are consistent with the hypothesis of partial transgenerational inheritance of tolerance to mercury in Huancavelica, Peru. This would generally benefit survival in the Anthropocene, the man-made world, we now live in.

The utility of hyperbaric oxygen therapy in post-transplant cyclophosphamide-induced hemorrhagic cystitis: a case report and review of the literature.

BACKGROUND: To date, there are only a few case reports of cyclophosphamide (Cy)-induced hemorrhagic cystitis (HC) in adult or pediatric allogeneic stem cell transplant (SCT) patients treated successfully with hyperbaric oxygen (HBO). In all the reported cases, Cy was used as a part of the conditioning regimen, rather than post-transplant for graft-versus-host-disease (GVHD) prophylaxis. More recently, the risk of HC in allogeneic SCT is further increased by the widespread use of post-transplantation cyclophosphamide (PTCy) as a highly effective strategy for GVHD prophylaxis. This is the first case reported of PTCy-induced HC successfully treated with HBO to the best of our knowledge. CASE PRESENTATION: In this article, we present a 58-year-old Caucasian male case of allogeneic SCT complicated by severe HC following PTCy, which was successfully treated with HBO, eliminating the need for cystectomy. CONCLUSION: HBO can be a safe, noninvasive, alternative treatment modality for PTCy-induced HC developing in allogeneic SCT patients.

Successful treatment of "accelerated" chronic lymphocytic leukemia with single agent ibrutinib: A report of two cases.

"Accelerated" chronic lymphocytic leukemia/small lymphocytic lymphoma (A-CLL) is a rare histological variant of CLL/SLL, which tends to exhibit an aggressive clinical behavior compared to CLL. Due to the rarity of A-CLL (<1% of all cases), the optimal management remains ill-defined. We report two cases of A-CLL from our institution, in which both relapsed following initial chemoimmunotherapy regimens. Both patients were treated with single agent ibrutinib, a Bruton's tyrosine kinase inhibitor (BTKi), and achieved rapid, deep and durable responses. With the absence of clear guidance on A-CLL treatment, BTKi agents should be considered in the frontline treatment of A-CLL.

Systemic vs. intrathecal central nervous system prophylaxis in primary adrenal/renal diffuse large b-cell LYMPHOMA: A multi-institution retrospective analysis and systematic review.

Primary adrenal lymphoma (PAL) and primary renal lymphoma (PRL) are rare extranodal lymphomas, predominantly of diffuse large B-cell lymphoma subtype. Primary adrenal and renal lymphomas (PARL) exhibit a high predilection for the central nervous system (CNS). Therefore, current guidelines support the use of CNS prophylaxis in PARL, particularly in cases of high-risk Central Nervous System International Prognostic Index (CNS-IPI). However, the route of administration (i.e. systemic vs. intrathecal chemotherapy) has not been clearly elucidated. With this in mind, we initiated an international collaboration and literature review to analyze 50 patient cases, 20 of which received CNS prophylaxis. Based on our analysis, we conclude that PARL may indicate a need for CNS chemo-prophylaxis in the form of systemic high-dose methotrexate (HD-MTX) over intrathecal methotrexate (IT-MTX), although IT-MTX may still have utility in certain cases.

The prognostic implications of tetraploidy/near-Tetraploidy in acute myeloid leukemia: a case series and systematic review of the literature.

The prognostic significance and optimal management of tetraploidy/near-tetraploidy acute myeloid leukemia (T/NT AML) remains unclear given its limited data. This is especially true after factoring in additional chromosomal alterations, which carry their own prognostic weight. Here, we analyze 128 cases of T/NT in AML from the literature along with two additional cases, which is the largest review of this subject to date. Based on our retrospective analysis, we found that regardless of the risk status attributed to cytogenetics, the prognosis of tetraploid or near-tetraploid AML is dismal and should be incorporated within the unfavorable risk group. Complete remission is paramount to survival in this population. Specific induction protocols for high-risk AML appear to have higher rates of complete remission in the T/NT AML population. Moreover, longer overall survival can be achieved with chemotherapy followed by allogeneic stem cell transplantation at first complete remission.

A Case Report with Severe Thrombocytopenia Induced by Axitinib.

Axitinib is an oral, second-generation tyrosine kinase inhibitor that is selective for vascular endothelial growth factor receptors (VEGFR). This agent is approved as monotherapy or in combination with immune checkpoint inhibitors for the treatment of metastatic renal cell carcinoma. Axitinib is associated with a safety profile very similar to other anti-VEGFR inhibitors but usually with fewer hematologic adverse events, due to the selectivity for VEGF. In this report, we presented a rare case of grade 4 axitinib-induced thrombocytopenia, not observed with other antiangiogenic therapies. We discuss the differential diagnostic work-up, the necessary multidisciplinary approach, and the successful management of the case.

Chronic Lymphocytic Leukemia with Translocation (2;14)(p16;q32): A Case Report and Review of the Literature.

We report the case of a young African American male with no significant past medical history presenting with low back and bilateral leg pain; presenting CBC and chemistries revealed elevated white blood cell count of 250,000, with anemia (Hb 6.8 g/dL) and thrombocytopenia (platelets 9 K/µL), and elevated LDH, 1008. Physical examination findings were notable for diffuse lymphadenopathy and lower extremity skin nodules. Interestingly the bone marrow biopsy revealed involvement by CLL/SLL with translocation (2;14)(p16;q32) and trisomy 12. The patient was treated with fludarabine-based chemotherapy and steroids for CLL-related ITP with excellent response. After three cycles of chemotherapy, all the enlarged lymph nodes and skin nodules disappeared, and patient had achieved complete hematologic response. In this paper we also reviewed the available literature of CLL patients with translocation (2;14).

A cohort study evaluating the role of surgery for lung metastases from colorectal cancer.

BACKGROUND/AIM: Surgery may be curative in some patients with metastatic colorectal cancer (mCRC). We analyzed the role of lung metastatectomy in this population. PATIENTS AND METHODS: In this retrospective cohort study, cases were defined as mCRC patients with lung metastases (LM's) who underwent metastatectomy. Controls had LM's but did not undergo resection. RESULTS: There were 28 cases and 46 controls. The median overall survival (OS) was 53 months among the cases and 26.3 months for the controls. The cases were more likely to have 1 or 2 lung metastases, unilateral versus bilateral LM's, metachronous versus synchronous presentation of LM's and more likely to have a carcinoembryonic antigen (CEA) level less than 10 ng/ml at diagnosis. The interval from diagnosis to the development of lung metastases was significantly longer in cases versus controls (22.9 versus 8.5 months). CONCLUSION: Patients selected using these criteria may have prolonged survival with therapy that includes lung metastatectomy.

Therapeutic vaccines in non-small cell lung cancer.

Non-small cell lung cancer (NSCLC) unfortunately carries a very poor prognosis. Patients usually do not become symptomatic, and therefore do not seek treatment, until the cancer is advanced and it is too late to employ curative treatment options. New therapeutic options are urgently needed for NSCLC, because even current targeted therapies cure very few patients. Active immunotherapy is an option that is gaining more attention. A delicate and complex interplay exists between the tumor and the immune system. Solid tumors utilize a variety of mechanisms to evade immune detection. However, if the immune system can be stimulated to recognize the tumor as foreign, tumor cells can be specifically eliminated with little systemic toxicity. A number of vaccines designed to boost immunity against NSCLC are currently undergoing investigation in phase III clinical trials. Belagenpumatucel-L, an allogeneic cell vaccine that decreases transforming growth factor (TGF-ß) in the tumor microenvironment, releases the immune suppression caused by the tumor and it has shown efficacy in a wide array of patients with advanced NSCLC. Melanoma-associated antigen A3 (MAGE-A3), an antigen-based vaccine, has shown promising results in MAGE-A3(+) NSCLC patients who have undergone complete surgical resection. L-BLP25 and TG4010 are both antigenic vaccines that target the Mucin-1 protein (MUC-1), a proto-oncogene that is commonly mutated in solid tumors. CIMAVax is a recombinant human epidermal growth factor (EGF) vaccine that induces anti-EGF antibody production and prevents EGF from binding to its receptor. These vaccines may significantly improve survival and quality of life for patients with an otherwise dismal NSCLC prognosis. This review is intended to give an overview of the current data and the most promising studies of active immunotherapy for NSCLC.

Clinical utility of aromatase inhibitors as adjuvant treatment in postmenopausal early breast cancer.

Breast cancer is the most frequently diagnosed malignancy in women, with over 200,000 new cases diagnosed each year. Adjuvant systemic endocrine therapy has demonstrated its benefits in reducing the risk of occult micro metastatic infiltration by preventing breast cancer cells from receiving endogenous estrogen stimulation. Initial adjuvant treatment with an aromatase inhibitor (AI) is considered the standard of care for most postmenopausal women with node-positive and high-risk node-negative estrogen receptor (ER)-positive breast cancer. Aromatase inhibitors (AIs) are generally preferred over tamoxifen due to their effectiveness in preventing breast cancer recurrence post surgery and when tamoxifen side effects are to be avoided. When compared with tamoxifen, AIs are associated with significantly improved disease-free survival, however no OS advantage has been noted. Potential toxicities such as bone loss, dyslipidemia, musculoskeletal and cardiovascular health issues should be taken into consideration when AIs are to be used.

Leiomyosarcoma of the splenic vein.

Leiomyosarcomas arising from the wall of blood vessels are rare and aggressive neoplasm. We report a case of a previously healthy 66-year-old woman who presented with intermittent abdominal pain, progressive constipation, and weight loss. Abdominal computed tomography showed a 12 cm solid heterogeneous tumor in the tail of the pancreas. The patient subsequently underwent surgical resection of the pancreatic mass. Surprisingly, histological and immunohistochemical analyses revealed leiomyosarcoma arising from the smooth muscle of the splenic vein. After surgery, she received adjuvant chemotherapy. One year later, there was no evidence of local recurrence. In this paper, we discuss the available information about leiomyosarcomas of splenic vein and its management.