Previous Hematologic Malignancy Research Articles

P479 The prevalence and risk factors of hematologic malignancy in patients with intestinal Behçet’s disease

Abstract Background The association of intestinal Behçet’s disease (BD) with the risk of hematologic malignancy is still unclear. We aimed to assess the prevalence and determine risk factors of hematologic malignancy in intestinal BD. Methods Using a cohort of patients with intestinal BD between 1997 and 2021, the prevalence and risk factors of hematologic malignancy were analysed by logistic regression analysis at inflammatory bowel disease centre of Severance Hospital, Seoul, Korea. Results Among 780 intestinal BD patients, 23 patients developed hematologic malignancy. Myelodysplastic syndrome (MDS) (n=12) was the most common hematologic malignancy, followed by aplastic anemia (AA) (n=7), leukemia (n=2), and lymphoma (n=2). Eight patients had developed hematologic malignancy before their intestinal BD diagnosis and 15 patients developed hematologic malignancy after their intestinal BD diagnosis. Of the 772 patients without previous hematologic malignancy, patients smoking history (p-value 0.019, odds ratio [OR] 49.513, 95% confidence interval [CI] 1.925-1273.4), history of at least one emergency room (ER) visit (p-value 0.025, OR 26.360, CI 1.501-462.92), and albumin lower than 3.3g/dL (p-value 0.046, OR 603.013, CI 0.108-328191.23) at diagnosis were positively associated with subsequent hematologic malignancy. Body mass index (BMI) (p-value 0.030, OR 0.569, CI 0.342-0.947) was negatively associated with hematologic malignancy. Conclusion The physicians who care for intestinal BD patients with risk factors should be aware and provide careful monitoring of the elevated risk of hematologic malignancy.

Expanded indications for lung transplantation for pulmonary complications after hematopoietic stem cell transplantation

ObjectivesPulmonary complications after hematopoietic stem cell transplantation (HSCT) are associated with poor survival and can be treated by lung transplantation (LT). However, the indications for LT in patients with pulmonary complications after HSCT remain unclear due to low number of cases. HSCT is frequently conducted for hematologic malignancies, which have different recurrence patterns from solid-organ malignancies. Some patients also experience ABO blood type changes post-HSCT. This study aimed to reassess the indication of LT for pulmonary complications post-HSCT, focusing on disease-free interval (DFI) and ABO-incompatibility. MethodsRetrospective chart reviews were performed in patients who underwent LT for post-HSCT pulmonary complications. In patients with previous hematologic malignancy, indication was based on estimated recurrence rate instead of DFI. Donors were selected based on the recipient anti-A/B antibody profile rather than ABO type. Post-LT survival and complication rates were examined. ResultsForty consecutive patients undergoing LT after HSCT (including 31 with previous hematologic malignancy) were analyzed. The median DFI between HSCT and LT was 64.5 months. Thirteen patients with previous hematologic malignancy had DFI <5 years but none experienced recurrence. There was no significant difference in 5-year post-LT survival between patients undergoing (74.7%) and not undergoing HSCT (68.4%). There was no significant difference in survival between patients with DFI ≥5 years (63.8%) and patients with DFI <5 years (83.3%). Five patients underwent LTs from major ABO-incompatible donors, but none developed incompatibility-related complications. ConclusionsIndications based on estimated recurrence rates and recipients' anti-A/B antibody profiles may increase the use of LT for patients after HSCT.

Genomic profiling of primary histiocytic sarcoma reveals two molecular subgroups.

Histiocytic sarcoma is a rare malignant neoplasm that may occur de novo or in the context of a previous hematologic malignancy or mediastinal germ cell tumor. Here, we performed whole exome sequencing and RNA-sequencing (RNA-Seq) on 21 archival cases of primary histiocytic sarcoma. We identified a high number of genetic alterations within the RAS/RAF/MAPK pathway in 21 of 21 cases, with alterations in NF1 (6 of 21), MAP2K1 (5 of 21), PTPN11 (4 of 21), BRAF (4 of 21), KRAS (4 of 21), NRAS (1 of 21), and LZTR1 (1 of 21), including single cases with homozygous deletion of NF1, high-level amplification of PTPN11, and a novel TTYH3-BRAF fusion. Concurrent NF1 and PTPN11 mutations were present in 3 of 21 cases, and 5 of 7 cases with alterations in NF1 and/or PTPN11 had disease involving the gastrointestinal tract. Following unsupervised clustering of gene expression data, cases with NF1 and/or PTPN11 abnormalities formed a distinct tumor subgroup. A subset of NF1/PTPN11 wild-type cases had frequent mutations in B-cell lymphoma associated genes and/or clonal IG gene rearrangements. Our findings expand the current understanding of the molecular pathogenesis of this rare tumor and suggest the existence of a distinct subtype of primary histiocytic sarcoma characterized by NF1/PTPN11 alterations with predilection for the gastrointestinal tract.

Outcomes of renal transplantation in patients with previous hematologic malignancies

Recommendations regarding the appropriateness of renal transplantation in patients with prior hematologic malignancies are limited. Given the lack of available data, studies are needed to assess which of these patients will maximally benefit from renal transplantation. This study was undertaken to describe the incidence of new or recurrent malignancy as well as patient and allograft survival, acute rejection, and serious infections in patients with prior hematologic malignancies receiving renal transplantation. This was a single center retrospective review of all adult patients with a previous hematologic malignancy who received a living or deceased renal transplantation between January 2009 and January 2016. Eight renal transplantation recipients with prior hematologic malignancies were identified and followed for a minimum of 3 years. Six patients received prior chemotherapy and five had a prior hematopoietic stem cell transplant. Median time from remission to transplant was 2.6 years. Three-year patient and allograft survival were 87% and 75%, respectively. Three patients were diagnosed with new cancers within 3 years post-renal transplantation; one of which died from cancer-related complications with a functioning allograft. There was concern for recurrent hematologic malignancies in two patients based on serologic studies, but, both of these patients were alive with functioning allografts at 3-year follow-up. Our experience suggests that renal transplantation can be successfully performed in select patients with prior hematologic malignancy but with a significant risk for de novo malignancy post-transplant, which may be associated with an overall poor prognosis. Decisions regarding renal transplantation candidacy should be made based on risk stratification and multidisciplinary discussions with patients, hematologists, and transplant providers.

A Case of Fatal Sepsis from Dog Exposure in a Young Stem Cell Transplant Patient

Capnocytophaga canimorsus is a fastidious, slow growing (up to 10 days), capnophillic gram-negative rod. It is most commonly associated with zoonotic exposure, particularly dog and cat bites. There is a growing body of literature for the recognition of septic shock caused by Capnocytophagia canimorsus in at-risk populations, including those with asplenia as well as current or previous hematologic malignancy. This is a case of a young man in remission from a hematologic malignancy, complicated by graft versus host disease, presenting many years later in fatal septic shock due to Capnocytophagia canimorsus infection.

Robust Engraftment with Mgta-456, a CD34+ Expanded Cell Therapy Product in Patients with Inherited Metabolic Disorders (IMD): Preliminary Phase 2 Trial Results

Background Mucopolysaccharidosis type IH (MPS1/Hurler Syndrome), cerebral adrenoleukodystrophy (cALD), metachromatic leukodystrophy (MLD) and globoid cell leukodystrophy (GLD) are fatal IMDs affecting the central nervous system treatable through allogeneic hematopoietic stem cell transplantation (HSCT). In the absence of a non-carrier HLA matched related donor, cord blood (CB) is the preferred source of cells in IMDs due to rapid availability and flexibility in matching. However, prolonged neutropenia and high graft failure rates present a challenge, particularly with reduced intensity conditioning regimens. MGTA-456 is produced from a single CB unit using an aryl hydrocarbon receptor antagonist in a 15-day expansion culture of CD34+ cells. In previous phase 1/2 studies, hematologic malignancy patients treated with myeloablative conditioning and MGTA-456, with median 324-fold CD34+ expansion, showed 100% engraftment with a 9 day reduction in time to neutrophil recovery. As higher CD34+ doses have been correlated with improved engraftment in IMD transplant patients, we hypothesize MGTA-456 may reduce duration of neutropenia and risk of graft failure and more rapidly correct the metabolic deficiency in IMD patients. Patients and Methods A Phase 2, open-label trial (NCT03406962) initiated in Feb 2018 is enrolling up to 12 patients Results Five patients have been treated per protocol to date (Figure 1). MGTA-456 contained a median 561-fold expansion of CD34+ cells after culture with a median infused CD34+ cell dose of 110 × 106 cells/kg and median total nucleated cell dose of 26.4 × 107 (Figure 2). The median duration of neutropenia was 1 day (range 0-9), in contrast to a median of 8 days for a historical cohort (Figure 3). Myeloid chimerism was ≥98% donor by day +14 in evaluable patients. Two patients developed autoimmune cytopenia, a known complication in IMD patients after HSCT, unrelated to MGTA-456. Time to discharge after transplant was a median of 19.5 days at time of reporting. Preliminary data from MPS1 patients demonstrated normalization of blood alpha-L-iduronidase enzyme activity and decreased urinary glycosoaminoglycan levels after transplant. Conclusions Treatment of IMD patients with MGTA-456 showed early and robust engraftment in all patients with marked reduction in days of neutropenia compared to a historical cohort. These preliminary data, in combination with the previous hematologic malignancy patients treated, suggest MGTA-456 substantially enhances engraftment and rate of neutrophil recovery.

P343 The electrophysiologic features of neurolymphomatosis

Background Neurolymphomatosis is defined as a malignant lymphoid infiltration of the peripheral nervous system. However, few studies revealed the clinical and electrophysiological features of neurolymphomatosis. The objective of this study is to investigate the clinical and electrophysiological features of neurolymphomatosis. Method We found eleven patients (six male and five female) with following two conditions from medical records at Severance hospital from January 2004 to February 2016: (i) patients with pathologically confirmed lymphoma or leukemia, and (ii) patient with the evidence of malignant cell infiltration of peripheral nervous system in imaging studies. We retrospectively analyzed eleven patients with neurolymphomatosis. Results The median age of neurologic symptom onset was 53 years (range, 36–70 years). Among eleven patients with neurolymphomatosis, ten had non-Hodgkin’s lymphoma and the most common subtype was diffuse large B-cell lymphoma and the other patient had acute lymphoblastic leukemia. Eight patients were expired and their mean survival time is eight months (range, 1–23 months) after the diagnosis of neurolymphomatosis. Neurologic deficits were presented as first clinical presentation of lymphoma in five (46%) patients and as relapse or progression of a previous hematologic malignancy in six (54%) patients. Patients frequently demonstrated cranial nerve involvement (six patients; 55%) and severe pain (ten patients; 91%). 18FDG-PET/CT scan excellently revealed abnormality in ten (91%) of eleven patients and malignant lymphoid cells usually infiltrated from root and/or plexus to distal peripheral nerve. Nerve conduction study (NCS) revealed partial conduction block in ten nerves and simple axonal degeneration in 26 nerves. The mean interval from neurologic symptom onset to test was significantly longer in nerves with simple axonal degeneration than that in the nerves with partial conduction block. All nerves demonstrated simple axonal degeneration in the test more than 25 days after symptom onset. Conclusions Partial conduction block on NCS may lead to misdiagnosis of neurolymphomatosis. However, if patients have progressive painful multiple mononeuropathies with cranial neuropathy, the possibility of neurolymphomatosis should be considered.