Outcomes with allogeneic stem cell transplant using cryopreserved versus fresh hematopoietic progenitor cell products.

BACKGROUND: Allogeneic hematopoietic stem cell transplant (alloHSCT) is a mainstay of treatment for hematologic malignancies such as acute leukemias and aggressive lymphomas. Historically, fresh hematopoietic progenitor cell (HPC) products have been preferred to cryopreserved products (cryo-HPC) due to concerns of loss of stem cell viability and number with the cryopreservation procedure. OBJECTIVE: We aimed to analyze the outcomes of patients who received cryo-HPCs during the COVID-19 pandemic and compare this against historical cohorts that received fresh HPC. STUDY DESIGN: A retrospective chart review was conducted on all adult patients who received a peripheral blood alloHSCT in British Columbia, Canada between June 2017 and November 2021. Baseline characteristics, Kaplan-Meier (KM) overall survival (OS), engraftment, and incidences of acute and chronic graft versus host disease were compared between patients who received cryo-HPCs and fresh HPCs. Univariable analysis followed by multivariable analysis was performed using a backward stepwise selection procedure to generate predictors of OS, cumulative incidence of relapse (CIR), nonrelapse mortality (NRM), and primary and secondary graft failure. RESULTS: Three hundred eighty-three patients were included in the analysis, with cryo-HPC representing 40%. Median viability was higher in the fresh-HPC group at 99.2% (IQR 98.3-99.5) versus cryo-HPCs at 97.0% (96.0, 98.6) (P < 0.01). The 12-month actuarial survivals were 77% in the fresh HPC and 75% in the cryo-HPC groups (P = 0.21). There were no differences between cryo-HPCs and fresh HPCs on univariable analysis of OS, CIR, or NRM. There was a shorter median time to platelet engraftment in patients receiving fresh HPC at 17 days (IQR 16, 20) versus cryo-HPC at 21 days (IQR 18, 29), P < 0.001. There was a shorter median time to neutrophil engraftment in the fresh HPC group at 17 days (IQR 14, 20) versus 20 days (17, 23), P < 0.001. Cryo-HPC accounted for 5 out of 6 cases of primary graft failure (P = 0.04), and 3 out of five cases of secondary graft failure (P = 0.39). There were no significant differences in acute GVHD between the fresh HPC and cryo-HPC groups (P = 0.34). The incidence of moderate or severe chronic GVHD was 32% in the fresh-HPC group and 17% in the cryo-HPC group (P < 0.001). In multivariable analysis, cryopreservation did not emerge as an independent predictor of OS, CIR, NRM, primary GF or secondary GF. However, viability <90% on arrival at our center was a significant predictor of OS (HR 5.3, 2.3-12.3, P < 0.01), primary graft failure (OR 36.3, 5.4-210.2, P < 0.01), and secondary graft failure (OR 18.4, 1.7-121.1, P < 0.01). CONCLUSIONS: Patients who received cryo-HPCs had similar OS and relapse rates to those who received fresh-HPCs but typically took 2-3 days longer to achieve engraftment of platelets or neutrophils and were associated increased primary graft failure. However, after accounting for multiple variables, cryopreservation was no longer a significant predictor of survival or engraftment while viability <90% emerged as an important predictor of OS, primary graft failure, and secondary graft failure. If confirmed, this suggests that viability on arrival at the infusion center may be a good quality control indicator used to identify HPC products that may warrant recollection if the risk of graft failure is sufficiently increased.

Mortality from Multiple Myeloma Within One Year Following Autologous Stem Cell Transplantation: Defining an Ultra-high Risk Population.

Despite improvements in therapy, approximately 5% of patients who undergo autologous stem cell transplantation (ASCT) experience early mortality (EM), death within 1 year of transplant (EM post-ASCT). Such patients tend to have few comorbidities suggesting their EM is owing to aggressive underlying disease. We sought to characterize this ultra-high risk population through a retrospective review of patients with newly diagnosed multiple myeloma (MM) treated with first-line ASCT. Patients who died within 1 year of ASCT were matched for age, sex, and year of transplant in a 1:2 fashion with a control group. Of 962 transplants performed between January 1, 2007, and May 1, 2019, 41 patients (4.3%) died within 1 year of ASCT from MM-related causes. In a multivariate analysis, anemia, hypercalcemia, high-risk cytogenetics, and elevated lactate dehydrogenase were associated with EM post-ASCT. Forty patients (97.6%) received at least 1 novel agent. Most patients with EM post-ASCT received second-line chemotherapy (80.5%), although survival from initiation of second-line chemotherapy was only 2.1 months. The primary reason for not receiving second-line therapy was rapid relapse. Clinical parameters reflecting disease burden, as well as high-risk cytogenetics, are associated with EM post-ASCT. These patients have a dismal overall survival despite significant advances in treatment of patients with relapsed or refractory myeloma. Further study of these ultra-high risk patients is required to improve disease management and may give further insights into the biology of relapse and resistance in myeloma.

Outcomes of Intermediate Risk Karyotype Acute Myeloid Leukemia in First Remission Undergoing Autologous Stem Cell Transplantation Compared With Allogeneic Stem Cell Transplantation and Chemotherapy Consolidation: A Retrospective, Propensity-score Adjusted Analysis.

INTRODUCTION: Optimal post-remission therapy (PRT) for intermediate risk acute myeloid leukemia remains an area of ongoing research. We aimed to retrospectively compare outcomes following autologous stem cell transplantation (autoSCT) with allogeneic SCT (alloSCT) and consolidation chemotherapy (CMT) in patients with intermediate-risk karyotype AML in first complete remission. PATIENTS AND METHODS: We compared overall survival (OS) and leukemia-free survival (LFS) using propensity score (PS)-adjusted analysis of patients receiving PRT with autoSCT, matched sibling (MSD) alloSCT, unrelated/mismatch (UD/MM) alloSCT, and CMT. We included patients diagnosed between 1984 and 2003 (period of autoSCT at our center) in CR1 following induction CMT and received at least 2 consolidative cycles. RESULTS: We identified 190 patients (62 MSD-alloSCT, 18 UD/MM-alloSCT, 30 autoSCT, and 80 CMT). Baseline characteristics were used for PS calculation and were well-balanced after weight adjustment. The median follow-up for patients surviving beyond 1 year was 8.7 years. We excluded 55 patients based on PS calculation. Adjusted multivariate hazard ratio (HR), 95% confidence interval (CI) and P-value for OS, considering CMT as reference, were: MSD-alloSCT (HR, 0.4; 95% CI, 0.2-0.8; P = .009), UD/MM-alloSCT (HR, 1.5; 95% CI, 0.6-3.9; P = .363), and autoSCT (HR, 1.2; 95% CI, 0.5-3.1; P = .666), respectively. Adjusted multivariate HR, 95% CI and P-value for LFS were MSD-alloSCT (HR, 0.3; 95% CI, 0.2-0.6; P < .001), UD/MM-alloSCT (HR, 1.1; 95% CI, 0.4-2.7; P = .854), and autoSCT (HR, 0.8; 95% CI, 0.3-2.2; P = .697), respectively. CONCLUSION: Patients with intermediate risk-karyotype acute myeloid leukemia who underwent MSD-alloSCT in first complete remission had the best outcomes. There were no survival differences between autoSCT, UD/MM-alloSCT, and CMT. Further study incorporating molecular changes and minimal residual disease status is warranted to select appropriate patients for autoSCT.

Novel agents improve survival of transplant patients with multiple myeloma including those with high-risk disease defined by early relapse (<12 months).

The treatment of multiple myeloma (MM) has changed with the advent of thalidomide, bortezomib, and lenalidomide, the so-called novel agents (NAs). Given the complexity of MM therapy in the NA era we pursued a population based study to assess for improvements in survival as well as to characterize the relevance of early relapse (within 12 months) and the International Staging System in this clinical setting. We reviewed our experience with 460 patients with MM treated with autologous stem cell transplant (ASCT) between 1988 and 2008, of whom 306 had relapsed. The cohort was divided into two groups based upon relapse pre-2004 and relapse during/after 2004 (2004+), which correlated to availability of bortezomib and lenalidomide. Improvements in both overall survival (OS) (median 32.0 months vs. 71.8 months; p < 0.001) and post-relapse survival (PRS) (median 15.2 months vs. 42.8 months; p < 0.001) correlated with the NA era. Exposure to NAs conferred a better PRS (median 35.7 months vs. 9.1 months; p < 0.001). Although all patients had improvements in survival, those who relapsed late continued to do better. Lastly, in the NA era, the ISS remains an important prognostic tool in relapse, but only in the late relapsing cohort.

A clinical phase II study of cisplatinum and vinorelbine (PVn) in advanced breast carcinoma (ABC).

OBJECTIVES: The effectiveness of cisplatinum and vinorelbine (PVn) as a salvage regimen in patients with metastatic breast cancer was reported in previous studies. This report is a pilot study assessing the antitumor efficacy and safety of this regimen as first line therapy for advanced breast cancer patients. METHODS: Thirty-five patients were enrolled: 22 with metastatic breast carcinoma and 13 with locally advanced breast carcinoma (stage III). A total of 4 cycles of PVn were planned. After the 4th cycle, patients with metastatic breast cancer received vinorelbine biweekly until disease progression or for a total of 12 cycles, whereas those with locally advanced breast cancer who showed complete or partial response underwent curative surgery. RESULTS: The overall response rate of our whole population was 74.29%. For the metastatic breast cancer group, the overall response rate was 64%, with a median survival of 19 months (range 2-36). For the locally advanced breast cancer group, the overall response rate was 92.3% with a median time to disease progression of 26 months (range 25-27). Toxicity was acceptable, and no treatment-related mortality was encountered. CONCLUSIONS: PVn is effective as first line treatment of advanced breast cancer with overall response rate of 64% in metastatic breast cancer and 92.3% in locally advanced breast cancer, and acceptable toxicity.

Pamidronate in the prevention of chemotherapy-induced bone loss in premenopausal women with breast cancer: a randomized controlled trial.

PURPOSE: Mortality from breast cancer has decreased in large part because of adjuvant chemotherapy. Sequelae of therapy include ovarian failure and bone loss, loss that would increase these patients' risk of fracture with aging. In this study, we assessed the efficacy of pamidronate in preventing such loss. PATIENTS AND METHODS: The study was a 1-yr randomized, double-blind, placebo-controlled trial comparing pamidronate 60 mg iv every 3 months with placebo in 40 premenopausal women with newly diagnosed breast cancer. Bone mineral density (BMD) of the spine and hip and remodeling markers were monitored over 1 yr. RESULTS: Over half of the subjects became amenorrheic, and those who did were 4 yr older than those who did not (P = 0.02). The mean difference in percent change in BMD at 12 months between the two treatment groups was 5.1% at the lumbar spine (P = 0.002) in the overall study group and 5% at the lumbar spine and 5.2% at the total hip in the amenorrheic subgroup (P < 0.03). Biochemical markers of bone remodeling did not differ between the two treatment groups, and treatment was well tolerated. CONCLUSION: Chemotherapy-induced amenorrhea is common with ensuing bone loss at the spine and hip. Pamidronate prevented bone loss at the spine and hip and was well tolerated.

Scrotal ulceration induced by all-trans retinoic acid in a patient with acute promyelocytic leukemia.

All-trans retinoic acid (ATRA) has been shown to improve the outcome in patients with acute promyelocytic leukemia compared with chemotherapy alone, but it is associated with adverse effects. We report the development of scrotal ulcer in a patient with acute promyleocytic leukemia (APL) within 10 days of treatment with ATRA at a dose of 40 mg orally twice daily. The ulcer did not respond to antibiotic treatment and healed shortly after withholding ATRA. The biopsy showed inflammation only, and other microbiological workup was negative.

Successful treatment of B-cell prolymphocytic leukemia with monoclonal anti-CD20 antibody.

We report a patient with B-cell prolymphocytic leukemia (PLL) who was treated successfully with the monoclonal anti-CD20 antibody (rituximab). The patient had recurrent infections due to relative neutropenia, secondary to bone marrow infiltration. After treatment with monoclonal anti-CD20 antibodies (rituximab) 375 mg/m(2) weekly for 4 weeks, complete remission was obtained. It was documented by normalization of peripheral blood counts, disappearance of organomegaly, and by molecular cytogenetics-fluorescent in situ hybridization (FISH) on bone marrow cells. She remains in complete remission 8 months following the discontinuation of treatment. This is the second reported case of successful treatment of B-cell PLL with rituximab.