A 2-Step Approach to Myeloablative Haploidentical Stem Cell Transplantation with Optimized T-Cell Dosing: Early Immune Reconstitution Leads to Better Outcomes

We developed a 2-step approach to myeloablative haploidentical HSCT in which patients receive a large fixed dose of cyclophosphamide (CY)-tolerized T cells separately frm the HSC infusion in the hopes of accelerating post HSCT immune reconstitution (IR). The uniformity of the T cell dosing facilitates comparison of patients without (low risk) and with (high risk) active malignancy at HSCT to ascertain the impact of disease status at HSCT on IR with fewer confounding effects from conditioning or T cell dosing

Mobilized Peripheral Blood Stem Cells Versus Unstimulated Bone Marrow As a Graft Source for T-Cell-Replete Haploidentical Donor Transplantation Using Post-Transplant Cyclophosphamide.

Purpose T-cell-replete HLA-haploidentical donor hematopoietic transplantation using post-transplant cyclophosphamide was originally described using bone marrow (BM). With increasing use of mobilized peripheral blood (PB), we compared transplant outcomes after PB and BM transplants. Patients and Methods A total of 681 patients with hematologic malignancy who underwent transplantation in the United States between 2009 and 2014 received BM (n = 481) or PB (n = 190) grafts. Cox regression models were built to examine differences in transplant outcomes by graft type, adjusting for patient, disease, and transplant characteristics. Results Hematopoietic recovery was similar after transplantation of BM and PB (28-day neutrophil recovery, 88% v 93%, P = .07; 100-day platelet recovery, 88% v 85%, P = .33). Risks of grade 2 to 4 acute (hazard ratio [HR], 0.45; P \u3c .001) and chronic (HR, 0.35; P \u3c .001) graft-versus-host disease were lower with transplantation of BM compared with PB. There were no significant differences in overall survival by graft type (HR, 0.99; P = .98), with rates of 54% and 57% at 2 years after transplantation of BM and PB, respectively. There were no differences in nonrelapse mortality risks (HR, 0.92; P = .74) but relapse risks were higher after transplantation of BM (HR, 1.49; P = .009). Additional exploration confirmed that the higher relapse risks after transplantation of BM were limited to patients with leukemia (HR, 1.73; P = .002) and not lymphoma (HR, 0.87; P = .64). Conclusion PB and BM grafts are suitable for haploidentical transplantation with the post-transplant cyclophosphamide approach but with differing patterns of treatment failure. Although, to our knowledge, this is the most comprehensive comparison, these findings must be validated in a randomized prospective comparison with adequate follow-up

Brain Zygomycosis in a Patient with High Risk Myelodysplastic Syndrome after Initiation of Chemotherapy

Introduction Zygomycetes are a group of fungi that can cause a variety of life-threatening infections particularly in immunocompromised patients. Zygomycosis manifests as a spectrum of diseases including stroke.1-3 We present a case of disseminated zygomycosis with central nervous system (CNS) involvement in a patient with myelodysplastic syndrome (MDS) after initiationof chemotherapy

From the Editors

We are proud to publish the 11th version of the Medicine Forum. Over the years, theforum has served as an opportunity for medical students and housestaff to pursue scholarly activities alongside learning clinical medicine. This peer-reviewed journal has also served as a platform for rising residents to gain invaluable experience with the editing process as well

Fatal Rituximab-Induced Nonspecific Interstitial Pneumonia: Case Report and Review of the Literature

Introduction: Rituximab is a chimeric anti-CD20 monoclonal antibody that is used to treat some hematological malignancies such as B-cell lymphomas, and various autoimmune diseases including immune thrombocytopenic purpura, systemic lupus erythematous, rheumatoid arthritis, and autoimmune hemolytic anemia. The most common side effects include fever, chills, and rigors. Respiratory complications such as cough, bronchospasm, sinusitis, and rhinitis have also been reported in 30% of patients in clinical trials.1 Rituximab-induced lung injury is a very rare but potentially fatal complication. We report a case of fatal single agent rituximab-induced nonspecific interstitial pneumonia to increase awareness about this serious side effect and review the current literature. Case Presentation: This case involves a 72-year-old female with stage IV marginal-zone lymphoma (diffuse nodal and splenic involvement) who required therapy due to transfusiondependent anemia and was initiated on single-agent rituximab (four weekly doses at a dose of 375 mg/m2). She tolerated the first two infusions well, but started to feel short of breath after her third infusion. By the time she arrived to the infusion center for her fourth dose, she was short of breath at rest and was found to be hypoxic to 68% on room air. Of note, the patient had COPD with a 30 pack-year smoking history, quit three years ago, but had no previous oxygen requirement. She was admitted to the hospital where she was started on broad-spectrum antibiotics and placed on five liters of oxygen delivered via nasal cannula. A chest CT scan with contrast showed extensive bilateral ground-glass opacities with interlobular septal thickening (Figure 1a). On the second day of admission, the patient became hypoxic to 70% on six liters of supplemental oxygen, but did not tolerate bilevel positive airway pressure so she was transferred to the medical intensive care unit. Methylprednisolone 125 mg every six hours was started intravenously for possible rituximab-induced lung reaction in the intensive care unit. A repeat CT scan of the chest two weeks later revealed improvement in the bilateral airspace opacitie

Worsening Autoimmune Neutropenia After Stopping Ibrutinib in a Patient With Chronic Lymphocytic Leukemia: Case Report and Review of Literature

Introduction Autoimmune cytopenia (AIC) is relatively common in patients with chronic lymphocytic leukemia occurring in 5-10% of patients during the course of their disease.1 Autoimmune hemolytic anemia (AIHA) constitutes the highest prevalence (5-10%) of CLL-associated AIC followed by idiopathic thrombocytopenic purpura (ITP) (2-5%), pure red cell aplasia (PRCA) (\u3c1%), and autoimmune neutropenia (AIN) (\u3c1%).2,3 The prevalence of AIN, however, may in fact be higher than reported due to a lack of awareness of the condition and difficulty in its diagnosis.4 Despite its rarity, autoimmune neutropenia can be a significant clinical challenge in patients with CLL and can increase the risk of infectious complications. Thus, the prompt diagnosis and resolution of CLL-associated AIN is essential to the management of these patients. Ibrutinib is a selective inhibitor of Bruton tyrosine kinase and induces a durable response in patients with CLL.5 The activity of ibrutinib in CLL-associated AIC is largely unknown as pivotal clinical trials excluded patients with AIC. We report a case of a patient with CLL who experienced worsening of AIN after discontinuing ibrutinib therapy. Given its immune modulatory effects, these findings suggest ibrutinib may have a role in controlling AIN in patients with CLL

From the Editors

As the Jefferson Forum embarks on its 11th issue a number of additions have beeninstituted. First, we are proud to announce new faculty collaborators with Dr. StevenHerrine, Dr. Danielle Duffy, Dr. Daniel Frisch, Dr. Anjali Avadhani, Dr. JosephDesimone and Dr. Edward Ruby. Our faculty has helped us with creating a new section of outstanding articles thatwe introduce in this issue. The “Best Of” designation allows us to highlight articlesthat were chosen by peer and faculty review as the best example of academic worksubmitted in each field of medicine. We hope that this addition will inspire moreresidents and faculty to get involved with the journal

Hematopoietic Cell Transplant Co-Morbidity Index (HCT-CI): Ability to Predict Outcomes in Haploidentical (HI) Hematopoietic Stem Cell Transplantation (HSCT)

Introduction We developed a 2 step approach to HI HSCT in which a fixed dose of allogeneic T cells are infused after reduced intensity (RIC) or myeloablative conditioning (HSCT step 1). After 2-3 days, cyclophosphamide (CY) 60 mg/kg/d x 2 is given to establish bidirectional tolerance. One day after the CY, a CD 34 selected stem cell product is infused (HSCT step 2). This approach has been associated with a low incidence of non-relapse mortality (NRM) resulting in a significant improvement in overall survival (OS) in patients (pts) undergoing HI HSCT at our institution. This abstract examined the predictability of this tool in pts undergoing the 2 step HI HSCT

Results of a phase I study of Bendamustine in Combination with Ofatumumab, Carboplatin and Etoposide (BOCE) for Refractory of Relapsed Aggressive B-cell Non Hodgkin\u27s Lymphomas (NHL)

Introduction: There are a number of regimens used to treat relapsed/refractory aggressive lymphomas and little consensus exists on the best salvage treatment. No regimen has shown clear superiority but uniformly there was an inferior outcome among patients who had relapsed after a prior rituximab containing regimen. Ofatumumab is a fully human IgG1k monoclonal anti-CD20 antibody. It recognizes a distinct epitope on the human CD20 molecule. In vitro studies with ofatumumab have shown more complement dependent cytotoxicity than rituximab. Bendamustine has single agent activity in relapsed aggressive lymphomas and has a favorable safety profile. Objectives: We conducted a phase I trial using a novel RICE-like salvage combination regimen in which ofatumumab is substituted for rituximab and bendamustine replaces ifosfamide in combination with carboplatin and etoposide (BOCE) to assess the safety and toxicity profile of this combination. The objective from the phase I part of this trial was to assess safety and tolerability of this combination

Outcomes of Older Patients Undergoing 2-Step Approach to Haploidentical and Matched Related Peripheral Blood Hematopoietic Stem Cell Transplantation (HSCT): A Single Institutional Experience

Introduction: HSCT is a curative option for many patients (pts) with hematological malignancies. Significant advances in supportive care and conditioning regimens over the past decade have allowed the extension of this therapy to older individuals. Information regarding the outcomes of this older subset of pts undergoing HSCT is limited, especially those undergoing haploidential (HI) HSCT. Objectives: To describe the outcomes of patients 60 years of age or older undergoing haploidential and matched related (MR) HSCT using the 2-step approach