Search

Stiff person syndrome (SPS) is a rare, debilitating neurological illness characterised by rigidity and spasms of the axial muscles, causing severe restrictions to mobility. SPS can be classic, partial or paraneoplastic. We report a case of a young woman who presented with seizures and painful spasms of the thoracolumbar muscles who was subsequently diagnosed with SPS. Serological work revealed glutamic acid decarboxylase (GAD) antibodies and imaging showed a large mediastinal mass. The patient underwent surgical resection of the mediastinal mass and final pathology revealed well-differentiated mediastinal liposarcoma. She received five sessions of plasma exchange and her neurological symptoms gradually improved after surgery. This case highlights a rare case of GAD antibody-positive paraneoplastic SPS associated with mediastinal liposarcoma.

Carfilzomib is a selective proteosome inhibitor that is commonly used in the treatment of relapsed or refractory multiple myeloma. Carfilzomib has been commonly associated with respiratory side effects. It can rarely also cause fatal pulmonary toxicity. We present a case of a man in his 50s with plasma cell leukaemia who was initiated on treatment with carfilzomib and dexamethasone. He developed severe pneumonitis requiring oxygen via a high-flow nasal cannula. After an extensive workup, a temporal relationship between the carfilzomib use and exacerbation of the pulmonary symptoms was found. Carfilzomib was permanently discontinued, and the patient was started promptly on methyl prednisolone with complete resolution of his symptoms. Due to the associated risk of mortality if not detected early, we wish to highlight this rare but serious pulmonary toxicity associated with carfilzomib that was managed with high-dose glucocorticoids.

Mantle cell lymphoma (MCL) is an incurable B cell non-Hodgkin's lymphoma with a variable clinical course. Central nervous system (CNS) involvement is a rare and dreaded complication in MCL. We report a case of leptomeningeal relapse of MCL that was successfully treated with a single-agent Bruton’s tyrosine kinase inhibitor. A man in his 50s with MCL was treated with six cycles of bendamustine–rituximab, achieving a complete remission (CR) and was subsequently placed on rituximab maintenance for 2 years. Four years later, he was hospitalised with symptoms of organic brain syndrome. Brain MRI and cerebrospinal fluid analysis confirmed CNS relapse of MCL. He was treated with dexamethasone, ibrutinib 560 mg/day and intrathecal cytarabine with improvement in neurological symptoms, and a follow-up MRI showed CR. The patient was later switched to acalabrutinib due to intolerance to ibrutinib. The patient is tolerating this regimen well, remaining in CR 3 years later.

Therapy-related acute myeloid leukemia (t-AML) usually stems from exposure of the bone marrow to cytotoxic chemotherapy and/or radiation therapy. t-AML is usually associated with poor overall survival, but occasionally t-AML can involve favorable-risk cytogenetics, including core binding factor AML (CBF-AML), which shows a recurrent chromosomal rearrangement with t(8;21) (q22;22) and ‘inv(16) (p13.1;q22)/t(16;16)(p13.1;q22)’, leading to ‘ RUNX1::RUNX1T1 and CBFB::MYH11’ fusion genes, respectively. Therapy-related CBF-AML (t-CBF-AML) accounts for 5–15% of CBF-AML cases and tends to have better outcomes than t-AML with unfavorable cytogenetics. Although CBF-AML is sensitive to high-dose cytarabine, t-CBF-AML has worse overall survival than de novo CBF- AML. The objective of this review is to discuss the available data on the pathogenesis, mutations, and therapeutic options in patients with t-CBF-AML.

A man in his 60s presented with a gradual progressive right-sided neck mass. Initial core biopsy was inconclusive and he was treated with a short course of oral prednisone for presumed sarcoidosis. Two months later, the patient developed worsening dysphagia, hoarseness of voice, dyspnea, and weight loss. Physical examination revealed bilateral cervical and right axillary lymphadenopathy. A right axillary lymph node excisional biopsy was performed and immunohistochemistry was diffusely positive for OCT4, SALL4, CD117, PLAP, confirming the diagnosis of metastatic seminoma. He received three cycles of bleomycin, etoposide, and cisplatin; bleomycin was omitted for the fourth cycle due to concern for toxicity. Restaging scans after four cycles of chemotherapy showed a favorable response to therapy. Unfortunately, the patient died from bleomycin pulmonary toxicity. This case illustrates a rare and atypical presentation of metastatic seminoma in an elderly patient.

Blast crisis (BC) is one of the most dreaded complications of chronic myeloid leukemia (CML). Fortunately, the incidence of BC has diminished markedly in the BCR-ABL tyrosine kinase inhibitor (TKI) era. The primary objective of initial treatment in BC is to achieve a second chronic phase (CP) and to proceed to an allogeneic stem cell transplantation (SCT) in eligible patients. The clinical outcome of patients with CML BC remains unsatisfactory, even with highly potent TKIs, as remissions are short lived and there is an unmet need for novel therapies. We provide a comprehensive summary reviewing the current management of Lymphoid BC.

326 Background: Renal transplant recipients (RTRs) are at an increased risk of developing solid organ malignancies. Given improved allograft survival and life expectancy, the incidence of prostate cancer (PC) in RTRs appears to be increasing. Previous studies have reported the incidence of PC among RTRs to be between 0.3% and 3.24%. Limited data is available on the clinical characteristics, treatment, predictive markers, and outcomes of PC in RTRs. Methods: We performed a single-center retrospective study of male RTRs who developed PC. We collected the following data on RTRs who underwent transplantation between January 1, 1999, and December 31, 2019: baseline demographics, cause of end-stage renal disease (ESRD), duration of dialysis prior to RT, type of RT (cadaveric vs. living donor), immunosuppressive regimen, interval from RT to diagnosis of PC, stage of PC, type of treatment received, allograft survival, and overall survival (OS) were collected. Results: Among 1093 male RTRs, 15 (1.37%) developed PC. The median age at diagnosis of PC was 60 (range, 49-75) years. Subject races were African American (n=7), Hispanic (n=3), White (n=3), and other (n=2). The median duration from transplant to diagnosis of PC was 72 (range, 12-156) months. PC was diagnosed at stage I in 13 patients, stage II in 1 patient, and stage IV in 1 patient. The management of these patients consisted of local radiation (LR) alone in 6 patients, LR with leuprolide therapy in 6 patients, and radical prostatectomy alone in 1 patient. The patient with stage IV PC was treated with leuprolide and abiraterone acetate and remains progression free at follow-up of 41 months. The 5-year OS for this cohort of patients was 73.3%. Allograft function was preserved in 13 patients 12 months after diagnosis of PC. No PC-related mortality was noted. Conclusions: The incidence of PC in our analysis appears to be consistent with prior published studies. Most of our RTRs with PC had early-stage disease with excellent 5-year survival. The current standard-of-care treatment modalities for PC appear to be effective in the management of these patients. Allograft function was preserved in the majority of RTRs with PC in this study. Further research is required to evaluate the predictive factors for developing PC in RTR.

MPN post-RT is a rare disease. There is little data on the clinicopathological features and outcomes of patients with post-RT MPN.The main objective of this study was to analyze the clinical outcome of MPN post-RT.This was a single-center retrospective study Settings: Patients who had post-RT MPN at Memorial Herman Hospital, Texas Medical Center.We reviewed 1998 patients who underwent RT between January 1, 1999, and December 31, 2019. Three cases of post-RT MPN were identified.None Main Outcome Measures: We analyzed the incidence, the interval between RT and MPN diagnosis, MPN treatment, and clinical outcome of patients with post-RT MPN.Among 1998 RT recipients, 3 cases (0.1%) of MPN were identified. All occurred in women with a mean age of 53 years. Races were African American (n=2) and white (n=1). Causes of end-stage renal disease were diabetes, hypertensive, and IgA nephropathy. Two patients received RT, and one patient simultaneous kidney and pancreas transplant. All three patients were on tacrolimus, mycophenolate, and prednisone for post-transplant immunosuppression. Two patients developed chronic myeloid leukemia (CML), and one had polycythemia vera (PV). The mean interval between RT and diagnosis of MPN was 9 years. Cytogenetics demonstrated JAK-2 mutation in the patient with PV and BCR-ABL translocation in the two CML patients. The CML patients received BCR-ABL tyrosine kinase inhibitors (TKIs; imatinib/dasatinib) and continue to have a major molecular response. The patient with PV remains on hydroxyurea (HU) and aspirin with excellent hematocrit control. Mycophenolate was discontinued in all three patients after the diagnosis of MPN. TKI and HU were well tolerated. No thrombotic events or leukemic transformation were reported. One CML patient developed cytomegalovirus colitis. No other infectious complications were noted. She also developed immune-related hemolytic anemia and thrombocytopenia that were successfully treated with glucocorticoids. All three patients still have preserved allograft function and are alive at a median follow-up of 42 months.MPN post-RT is rare. Standard-of-care therapies for MPN are well tolerated. Further studies are required to explore the pathophysiology and outcomes of MPN in RT recipients.

e19019 Background: Cytarabine-anthracyclines (7+3) induction chemotherapy (IC)) has been the mainstay therapy for over four decades and it remains the standard AML IC regimen internationally. Triplet IC using purine analogues (fludarabine/cladribine) in combination with cytarabine and idarubicin (FIA/CLIA) is superior to the standard 7+3 regimen, but challenging to administer in general hospital settings due to myelosuppression. We reviewed AML IM rate in patients induced with (fludarabine/cladribine) combined with cytarabine and idarubicin (FIA/CLIA) at Memorial Hermann Hospital, Texas Medical Center (MHH at TMC). Patients and Methods: Of 44 AML reviewed records from January 2013 to January 2022, 40 received 5 days FIA/CLIA IC, and four 3-4 days due to age and comorbidities. For clinical characteristics see Table. Results: Median age was 51.5 years (range: 18-68). Three died before assessment. After 1 cycle the composite CR (CR+ CR i) was 82.9% (34/41) and 87.8% (36/41) after 2 cycles. MRD negative composite CR was 92%. Four patients had adverse risk cytogenetics and primary induction failure (modified FIA). 37% had febrile neutropenia. 25% had bacteremia with 15% requiring ICU admission and 4% mechanical ventilation. The 30-day induction mortality was 9%. Conclusions: FIA/CLIA has a higher CR rate than ‘3+7’ (which historically is 60%). The 30-day induction mortality in non-academic centers is about 30%. Given the fact that in AML achieving a CR is the most important factor to improve survival, with adequate treatment expertise, triplet IC regimen can be safely administered with a low induction mortality. [Table: see text]

10528 Background: Renal transplant (RT) recipients are at an increased risk of developing renal cell carcinoma (RCC), mainly due to iatrogenic immunosuppression and changes in immune surveillance. Most RCCs in RT recipients arises from the native kidney, but rarely may arise from the allograft. RCC post-RT can adversely affect allograft function and long-term survival. Screening for RCC in RT recipients is controversial and is not routinely done. Methods: We performed a retrospective chart review of RT recipients who underwent transplantation between January 1, 1999, and December 31, 2019. The following data were collected: Baseline demographic variables, cause of end-stage renal disease (ESRD), duration of dialysis prior to RT, type of RT (cadaveric vs. living donor), immunosuppressive regimen, site of RCC (native kidney vs transplanted kidney), time from RT to diagnosis of RCC, stage and Fuhrman grade, tumor histology, RCC treatment, and RCC-related mortality. RCC stage at diagnosis and survival were compared between patients who were screened versus those who were not. Results: Among 1998 RT recipients who underwent transplantation at Memorial Hermann Hospital (MHH) Texas Medical Center (TMC); 16 patients (0.8%) developed RCC. An additional 4 patients with RCC who underwent RT elsewhere but received follow up at MHH TMC were also included. Therefore, a total of 20 patients with post-RT RCC were identified, of whom 75% were men. Subject races included White (20%), Black (50%), Hispanic (20%), and Asian (10%). The median age was 56 years. Median duration of dialysis prior to RT was 36 months (range, 1–120). Median time to RCC diagnosis post-RT was 96 months (range, 16–312). Histologies included clear cell (75%), papillary (20%), and chromophobe (5%) RCC. RCC developed in the native kidney in 60% and in the allograft in 40% of the patients. Post-RT RCC patients were divided into those who underwent regular screening (n = 12) and no screening (n = 8). The regular screening group (n = 12) underwent ultrasound or computerized tomography annually or every 2 years. All of these patients had early-stage disease at presentation: stage I (n = 11) or II (n = 1). All patients who had RCC detected by screening were cured by nephrectomy (n = 10) or cryotherapy (n = 2). In patients who had no screening post RT, 37.5% had stage I, 25% had stage III, and 37.5% had stage IV RCC. Two patients with stage IV RCC died from metastatic disease. The RCC-related mortality was 0% in patients who were screened, compared to 25% in patients who had no screening. Conclusions: All RT recipients who had RCC diagnosed based on screening had an early diagnosis and no RCC-related mortality. Screening for RCC in RT recipients is an effective tool for early diagnosis and to reduce RCC-related mortality. Further research into the cost-effectiveness of screening is imperative.

e19581 Background: An estimated 2-3% of individuals who undergo advanced heart failure therapies, such as left ventricular assist devices (LVAD) or orthotopic heart transplantation (OHT), have an antineoplastic-related cardiomyopathy. We investigated the incidence and clinical outcomes of non-ischemic or dilated cardiomyopathies on LVAD patients who have been diagnosed with lymphomas or leukemias in our institution between years 2015 - 2022. Methods: We found four cases of patients with newly diagnosed hematological malignancy who had existing underlying LVAD-dependent cardiomyopathy in our center. One patient was excluded due to loss to follow up. The other three patients were treated in the heart failure unit while concurrently managed by LVAD specialists. One patient required administration of continuous 72hr-infusion of doxorubicin to minimize the risk of right-sided ventricular failure. The response to treatment was assessed with use of PET-CT scans, bone marrow biopsies and serological markers per standard of care guidelines. Results: The median age was 54.6 years. Two were African Americans, one Caucasian and one Hispanic (lost to follow up). All patients were males. Of these four individuals, two were diagnosed with Non-Hodgkin Lymphomas (one Peripheral T-cell lymphoma, one Diffuse Large B-cell lymphoma), one with Chronic Lymphocytic Leukemia (CLL) and one with Acute Promyelocytic Leukemia (APL). Three patients completed or have ongoing chemotherapeutic treatment. All have achieved complete remission (CR 3/3) of their diseases. Conclusions: To date, there is no significant volume of data showing the administration of chemotherapy on patients with concurrent LVAD-dependent cardiomyopathies. The Peripheral T-cell lymphoma patient received anthracycline therapy via a continuous 72-hour infusion with close LVAD monitoring at the heart failure unit. After completion of total 6 cycles in 2021, he still is in complete remission. Our CLL patient, has also completed 5 cycles of rituximab and venetoclax while also maintaining disease remission. The APL patient has completed 5 cycles of arsenic trioxide and ATRA with also a complete remission of his leukemia. LVAD-dependent cardiomyopathy patients concurrently diagnosed with malignant hematological diseases, can be considered for treatment with antineoplastic therapies. Durable remission rates can be achieved while undergoing aggressive cardiovascular care.

Warm autoimmune haemolytic anaemia mediated by warm agglutinins is a rare and heterogeneous disease which can be idiopathic or secondary to an underlying disease. Primary sclerosing cholangitis is a chronic autoimmune cholangiopathy that is very rarely associated with haemolytic anaemia. Infections can also act as triggers for immune haemolytic anaemia. Here, we report a case of a woman in her 50s with a history of primary sclerosing cholangitis and a positive direct antiglobulin test with no evidence of haemolysis who developed overt warm autoimmune haemolytic anaemia in the setting of cholangitis and Klebsiella pneumoniae bacteraemia. She was treated conservatively with appropriate antibiotics and cautious red blood cell transfusion with complete resolution of haemolysis; immunosuppression was avoided given sepsis on presentation. This case highlights a rare association of warm immune haemolytic anaemia in the setting of K. pneumoniae bacteraemia and the role of a tailored treatment approach to treat this heterogeneous disease.

Ecthyma gangrenosum is a rare and highly lethal cutaneous infection classically associated with Pseudomonas aeruginosa bacteremia. We report a 58-year-old man with multiple myeloma receiving chemotherapy who presented with 2 days of painless left periorbital swelling that rapidly progressed to a blackish eschar. His absolute neutrophil count was 0.10/mm(3); platelet count, 14,000/mm(3); and hemoglobin, 6 g/dL. Computed tomography showed diffuse left periorbital cellulitis. Blood cultures grew pan-sensitive Pseudomonas aeruginosa, and the patient died from sepsis and multiorgan failure.

Extraosseous Ewing’s sarcoma is a rare and aggressive malignant tumor with a poor prognosis. The pancreas is an extremely uncommon primary site, with only 27 cases that have been published worldwide. We report a 26-year-old female who presented with 5 days of left upper quadrant pain, nausea, and vomiting. On examination, she was anicteric and had epigastric and left upper quadrant tenderness without guarding, rebound tenderness, or a palpable mass. She had slightly elevated serum aminotransferase and lipase levels. Abdominal computerized tomography revealed a multilobulated tumor arising from the body and tail of the pancreas. A biopsy confirmed a small round cell tumor, and immunohistochemistry was positive for CD99 in approximately 70% of the tumor cells. A fluorescence in situ hybridization (FISH) assay showed a 22q12 rearrangement. She was diagnosed with extraosseous Ewing sarcoma of the pancreas and underwent multiagent neoadjuvant chemotherapy followed by surgical resection, but subsequent imaging revealed evidence of systemic disease progression. She chose to go on hospice care and died a few weeks later.

e19578 Background: Secondary HLH in adults is associated to infections, malignancies, and autoimmune disorders. HLH in children has been the basis for the management and treatment of HLH in adults. Despite their clinical similarities there are fundamental differences. Children’s HLH is caused by gene mutations in granule-mediated cytotoxicity while secondary HLH does not have known apparent genetic causes. This may affect the clinical outcomes based in how we approach the diagnosis and management of secondary HLH in adults. Methods: We reviewed 49 cases of secondary HLH at our institution over a five-year period. Patients median age was 47 years, with 31 males, 18 females. Fifteen were Caucasian, 10 Asians, 8 African American and 15 Hispanics. One was not specified. Results: Fever, hyperferritenemia and cytopenia correlated with 100% elevation of sCD25R, the most important biomarker of HLH. Patients with these three criteria were urgently treated with dexamethasone-etoposide (HLH-94 protocol) or dexamethasone alone (autoimmune related) while completing identification of other criteria described in the pediatric population together with treatment of the secondary cause. Conclusions: Secondary HLH is not rare. Etoposide and dexamethasone (preferred dose:40 mg total/day initially) are the most important current therapeutic approaches. Secondary HLH must be treated urgently and independently of the secondary cause. Treatment should not be delayed awaiting results of sCD25R, NK-cell activity and presence of hemophagocytosis in the bone marrow (often absent). Further work needs to be done to elucidate the physiopathology of secondary HLH.[Table: see text]

Background: Immune checkpoint inhibitors have changed the therapeutic milieu for patients with metastatic melanoma. However, their use may promote autoimmunity in virtually any organ in the body due to the blockade of intrinsic immune down regulators such as cytotoxic T-lymphocyte antigen- 4 (CTLA-4), programmed cell death 1 (PD1) or its ligand (PDL1). Immune mediated adverse neurological events are rare with these agents, however, and are seen in < 1% of treated patients. We report a patient with immune checkpoint inhibitor associated autoimmune encephalitis, with complete clinical recovery after treatment.Case Report: A 49-year-old female with metastatic melanoma currently on nivolumab therapy but recently on ipilimumab/nivolumab combined therapy presented with a new headache. She also reported associated confusion, loss of balance, personality changes and language difficulty. Magnetic resonance imaging of the brain did not reveal any evidence of metastasis, infarct, meningitis, or encephalitis. Lumbar puncture revealed an elevated protein level and pleocytosis, with a normal glucose level. She was started on empiric glucocorticoid therapy with a presumptive diagnosis of immune checkpoint inhibitor associated autoimmune encephalitis. She improved considerably by day 3 of treatment with complete resolution of neurological symptoms by day 5.Conclusion: Immune checkpoint inhibitors are increasingly important in cancer immunotherapy as they can cause sustained remissions in patients with metastatic melanoma and other malignancies. Because these drugs block immune-regulatory targets, they can lead to enhanced activation of immune system resulting in immune-related adverse events. Autoimmune encephalitis is a rare immune-related adverse event associated with immune checkpoint inhibitors. The incidence of autoimmune encephalitis is higher with combination or sequential CTLA-4 (ipilimumab) and PD1(nivolumab) inhibitor therapy than with monotherapy. With more widespread use of immunotherapy, it is important for clinicians to be aware of this rare and reversible cause of encephalitis. Early recognition and prompt initiation of immunosuppressive therapy with glucocorticoids is essential to enhance neurological recovery.

Balamuthia mandrillarisis a rare cause of granulomatous meningoencephalitis associated with high mortality. We report a 69-year-old Caucasian female who presented with a 3-day history of worsening confusion and difficulty with speech. On admission, she was disoriented and had expressive dysphasia. Motor examination revealed a right arm pronator drift. Cerebellar examination showed slowing of finger-nose testing on the left. She was HIV-negative, but the absolute CD4 count was low. Neuroimaging showed three cavitary, peripherally enhancing brain lesions, involving the right frontal lobe, the left basal ganglia, and the left cerebellar hemisphere. She underwent right frontal craniotomy with removal of tan, creamy, partially liquefied necrotic material from the brain, consistent with granulomatous amoebic encephalitis on tissue staining. Immunohistochemical studies and PCR tests confirmed infection withBalamuthia mandrillaris. She was started on pentamidine, sulfadiazine, azithromycin, fluconazole, flucytosine, and miltefosine. The postoperative course was complicated by an ischemic stroke, and she died a few weeks later.

Treatment of cancer patients with olaparib (PARP inhibitor) is associated with an increased risk of anemia, which is seen in a majority of treated patients. However, symptomatic anemia requiring transfusion is rare. Olaparib-induced anemia can be secondary to bone marrow suppression, hemolysis or folate deficiency. We report a case of new onset severe folic acid deficiency anemia in a patient with breast and relapsed fallopian tube cancer being treated with olaparib. Complete blood count on admission showed a hemoglobin of 4.2 g/dl and serum folate was undetectable (< 1.6 ng/ml; reference range 7-31.4 ng/ml). This is the second report of olaparib-induced folate deficiency anemia. She received three units packed red cell transfusion and parenteral folic acid supplementation and improved symptomatically. This case highlights the importance of recognizing folate deficiency as a reversible cause of anemia with PARP inhibitor therapy.

Metastasis to the anterior cranial fossa from solid tumors is very unusual. We describe a 72-year-old male with history of locally advanced prostate cancer who presented with sequential bilateral vision loss, initially misdiagnosed and mistreated as giant cell arteritis. Neuroimaging eventually revealed an extra-axial soft tissue mass in the planum sphenoidale exerting a pressure effect on the cisternal segments of the optic nerves. He underwent surgical excision of the mass to try to improve his vision. Biopsy results confirmed high grade metastatic adenocarcinoma of the prostate. He was started on high dose glucocorticoids and radiation therapy and his visual symptoms improved. Patients with metastatic prostate cancer can develop cranial nerve deficits secondary to metastatic involvement of the skull base. Early recognition and appropriate therapy is essential to prevent permanent neurological impairment.