S. Ganguly

A risk-based approach to optimize autologous hematopoietic stem cell (HSC) collection with the use of plerixafor

Autologous hematopoietic stem cell (HSC) transplant is an effective treatment for patients with hematological malignancies. Unfortunately, 15–30% of patients fail to mobilize a sufficient number of HSCs for the transplant. Plerixafor is now used as a salvage mobilization regimen, with good success. We describe here a risk-based approach for the use of plerixafor, based on the circulating CD34+ cell count and the CD34+ cell dose collected after 4 days of G-CSF, that identifies potential poor HSC mobilizers upfront. A total of 159 patients underwent HSC collections using this approach. Of these, 55 (35%) were identified as high risk owing to low CD34+ cell number or low yield on day 1 of collection, and received plerixafor on the subsequent days of collection. Of the 159 patients, 151 (95%) were able to provide adequate collections with the first mobilization attempt in a median of 1.7 days using this approach. Of the eight who failed initial mobilization, 5 successfully underwent re-mobilization with plerixafor and G-CSF and 3 (1.9%) were mobilization failures. This approach helped to control the overall cost of HSC collections for our BMT program by decreasing the need for remobilization, reducing the number of collection days and avoiding the use of plerixafor in all patients.

Fatal GvHD induced by PD-1 inhibitor pembrolizumab in a patient with Hodgkin's lymphoma.

290. 10 Armand P, Nagler A, Weller EA, Devine SM, Avigan DE, Chen Y-B et al. Disabling immune tolerance by programmed death-1 blockade with pidilizumab after autologous hematopoietic stem-cell transplantation for diffuse large B-cell lymphoma: results of an international Phase ii trial. J Clin Oncol 2013; 31: 4199–4206. 11 Villasboas JC, Ansell SM, Witzig TE. Targeting the PD-1 pathway in patients with relapsed classic Hodgkin lymphoma following allogeneic stem cell transplant is safe and effective. Oncotarget (e-pub ahead of print 3 February 2016; doi:10.18632/oncotarget.7177). 12 Mori S, Ahmed W, Patel RD, Dohrer AL. Steroid refractory acute liver GvHD in a Hodgkins patient after allogeneic stem transplant cell transplantation following treatment with anti PD-1 antibody, nivolumab, for relapsed disease. Biol Blood Marrow Transplant 22: S392–S393. ABVD (6 cycles) ICE x 2 Autologous transplant: BEAM Brentuximab Allogeneic transplant: Flu/TBI Brentuximab Pembrolizumab Death from GVHD Diagnosis 7 Months relapse 10 Months 27 Months progression 31 Months 43 Months relapse 58 Months relapse 60 Months death Figure 1. Clinical course of the patient. Letter to the Editor

Giant anal condylomatosis after allogeneic bone marrow transplantation: a rare complication of human papilloma virus infection

Abstract: Condyloma acuminata or genital warts are caused by human papilloma virus (HPV). Ongoing proliferation of HPV in patients with congenital or acquired immunodeficiency states leads to the development of rapidly progressive and sometimes locally invasive tumor with or without dysplasia. Aggressive treatment, diagnostic immuno‐typing, and follow‐up are necessary in patients with ongoing immunosuppression. We report a case of giant ano‐genital condylomatosis due to HPV types 6 and 11 in a patient with chronic myeloid leukemia after allogeneic bone marrow transplantation. The tumor was successfully treated with surgical excision and local application of 5% imiquimod cream.

Phase IIa cross-over study of propylene glycol-free melphalan (LGD-353) and alkeran in multiple myeloma autologous transplantation

Propylene Glycol-Free melphalan HCL for Injection (PGF-Mel) is a new formulation that incorporates Captisol, a specially modified cyclodextrin, to improve melphalan stability. In this phase IIa, open-label, randomized, cross-over design bioequivalence study, the pharmacokinetics of PGF-Mel were compared with the marketed formulation of melphalan, or Alkeran. Patients received half of the total dose of melphalan in the form of Alkeran and the other half in the form of PGF-Mel in an alternating manner. The pharmacokinetic measures were determined using WinNonlin 6.2 and bioequivalence was assessed using log-transformed systemic exposure parameters. Twenty-four patients, 11 females and 13 males, were enrolled between 4 February 2010 and 16 May 2011 at The University of Kansas Medical Center and The University of Kansas Cancer Center. The median age of enrolled subjects was 58 years (range: 48–65). All patients achieved myeloablation 3 days post autologous graft followed by successful neutrophil engraftment with a median of 11 days after transplant. Pharmacokinetic analysis showed that PGF-Mel was bioequivalent with Alkeran and also revealed that maximum plasma concentration (Cmax) and area under the plasma concentration−time curve (AUC) were higher (~10%) after PGF-Mel administration. In conclusion, PGF-Mel is considered bioequivalent to Alkeran while also demonstrating a marginally higher systemic drug exposure.

Erythropoietin modulation is associated with improved homing and engraftment after umbilical cord blood transplantation

Umbilical cord blood (UCB) engraftment is in part limited by graft cell dose, generally one log less than that of bone marrow (BM)/peripheral blood (PB) cell grafts. Strategies toward increasing hematopoietic stem/progenitor cell (HSPC) homing to BM have been assessed to improve UCB engraftment. Despite recent progress, a complete understanding of how HSPC homing and engraftment are regulated is still elusive. We provide evidence that blocking erythropoietin (EPO)-EPO receptor (R) signaling promotes homing to BM and early engraftment of UCB CD34+ cells. A significant population of UCB CD34+ HSPC expresses cell surface EPOR. Exposure of UCB CD34+ HSPC to EPO inhibits their migration and enhances erythroid differentiation. This migratory inhibitory effect was reversed by depleting EPOR expression on HSPC. Moreover, systemic reduction in EPO levels by hyperbaric oxygen (HBO) used in a preclinical mouse model and in a pilot clinical trial promoted homing of transplanted UCB CD34+ HSPC to BM. Such a systemic reduction of EPO in the host enhanced myeloid differentiation and improved BM homing of UCB CD34+ cells, an effect that was overcome with exogenous EPO administration. Of clinical relevance, HBO therapy before human UCB transplantation was well-tolerated and resulted in transient reduction in EPO with encouraging engraftment rates and kinetics. Our studies indicate that systemic reduction of EPO levels in the host or blocking EPO-EPOR signaling may be an effective strategy to improve BM homing and engraftment after allogeneic UCB transplantation. This clinical trial was registered at www.ClinicalTrials.gov (#NCT02099266).

BU, melphalan and thiotepa as a preparative regimen for auto-transplantation in Hodgkin’s disease

BU, melphalan and thiotepa as a preparative regimen for auto-transplantation in Hodgkin’s disease

Late-Onset Intestinal Perforation in the Setting of Posttransplantation Microangiopathy: A Case Report

Intestinal perforation in the setting of posttransplantation microangiopathy (TMA) is a very rare event and might be considered a terminal event of intestinal microangiopathy (i-TMA), a rather rarely recognized posttransplantation complication, as it overlaps with the more common intestinal graft-versus-host disease (GVHD). Cases of i-TMA described in literature occurred within with first 100 days posttransplantation or shortly thereafter. In this report, we describe a case of late-onset intestinal perforation that occurred in the setting of systemic microangiopathy more than a year after allogeneic transplantation. In our case, the patient poorly responded to treatment secondary to refractory mircoangiopathy.

Coexistent Non-Hodgkin's Lymphoma and Renal Cell Carcinoma in aPatient with Von Hipple-Lindau Disease: A Case Report

Von Hippel-Lindau (VHL) disease is an autosomal dominant syndrome that, due to loss of tumor suppressor gene function, predisposes affected individuals to various benign and malignant tumors including renal cell cancer. In contrast, lymphomas are a varied group of clonal diseases arising from a lymphocyte progenitor and can affect any site of the lymphatic system. We present the case of a 56 year old female with Von Hippel-Lindau disease and clear cell renal carcinoma (CCRC), who developed a nasopharyngeal mass with cervical and submandibular lymphadenopathy subsequently proven to be a Non Hodgkin’s lymphoma (NHL). Though the association between VHL and renal cell cancer is significant, a mechanism linking these two diseases has previously been unknown. To the best of our knowledge, this is the first reported case of a patient presenting with coexistent VHL and NHL. In an effort to explain this rarity, we propose that a defective VHL allele may serve as a possible link between VHL and RCC, thus leading to an environment that would favour the development of a malignant clone, our patient’s NHL.

Intestinal ischemia after allogeneic stem cell transplantation: a report of four cases.

Gastrointestinal ischemia after allogeneic bone marrow transplantation is a rare complication not well-described in the literature. Herein we retrospectively review charts of four patients who developed intestinal ischemia after allogeneic bone marrow transplantation at our institution. The patients were found to be predominately younger males who presented with nonspecific abdominal pain. Graft-versus-host disease was a common finding among all patients. Laboratory values suggestive of microangiopathy were present in two patients. Obesity and hypertriglyceridemia were cardiovascular risk factors found in these patients. The development of thrombotic microangiopathy and cardiovascular risk factors after allogeneic bone marrow transplantation may predispose patients to gastrointestinal ischemia and may portend a poor prognosis.

Role of transfusion in stem cell transplantation: a freedom-from-transfusion (FFT), cost and survival analysis

Abstract Background: Transfusion of blood products is often necessary for patients undergoing stem cell transplantation (SCT). The need for red cell and platelet transfusion may vary significantly depending on the type of transplantation and underlying disease. Methods: In an attempt to evaluate the need and volume of transfusions in patients undergoing SCT at University of Kansas Medical Center, the authors retrospectively evaluated the transfusion data of all patients who received SCT between 2000 and 2005. Results: A total of 138 (90%) out of 154 patients undergoing autologous SCT and 24 (43%) out of 56 patients with allogeneic SCT exhibited total hematopoietic engraftment and freedom from transfusion (FFT). Time to achieve FFT (median; range) for RBC units for autologous SCT (12; 0–183) was significantly shorter compared with allogeneic SCT (16.5; 0–373). Number of RBC units (median; range) transfused were significantly less in patients undergoing autologous SCT (4; 0–26) compared to patients undergoing allogeneic SCT (6.5; 0–54). The median cost of transfusion was significantly higher in patients undergoing allogeneic SCT (red cell: