Impact of COVID-19 on peripheral stem cell collection and preservation at a hematopoietic cell transplant center in India: Experience 2020

Abstract Introduction: Autologous stem cell transplant (ASCT) is considered standard of care in young and fit patients with newly diagnosed multiple myeloma. ASCT has shown to improve depth of response, progression free survival and overall survival compared to systemic therapy alone in myeloma patients (Harousseau et al. New England Journal of Medicine). Proximity to a stem cell transplant center may influence the utilization of this therapeutic option in transplant eligible multiple myeloma patients. Our cancer center did not have a stem cell transplant program in the 100-mile driving radius. The goal of this study was to assess the referral patterns and utilization of ASCT in newly diagnosed, young (age <65 years) multiple myeloma patients in a setting where patients are lacking proximity to a transplant center. Methods: The study was an IRB-approved retrospective cohort study. Patients between 18 and 65 years of age at the time of diagnosis who were diagnosed with multiple myeloma between January 1, 2014, and December 31, 2020, were included. Data including age at diagnosis, sex, race, zip code, treatment regimen, clinical data-including referral to a transplant center, stem cell collection and transplant-were collected and analyzed. Staging was calculated using lab values at the time of diagnosis or within 2 weeks of starting treatment. Date of diagnosis was defined as the date of bone marrow biopsy confirming systemic disease. All frequency and descriptive analyses were performed using SPSS Version 26 (Armonk, NY: IBM Corp.) Results: There were n = 62 patients that met the study inclusion criteria. Patients were mainly white (86%) and male (58%) with an average age at diagnosis of 55.9 (SD = 6.83) years. All patients (n = 62, 100%) lived at zip codes that were more than 100 miles from the closest transplant center. ISS staging showed 37% (n = 23, 95% CI 25% - 50%), 29% (n = 18, 95% CI 18% - 42%), and 18% (n = 11, 95% CI 9% - 30%) to have stage I, II, and III disease respectively. Twelve patients (n = 12, 19.4%, 95% CI 10.4% - 31.4%) had insufficient data for staging. The most common first line regimens were bortezomib, lenalidomide, and dexamethasone (n = 39, 62.9%, 95% CI 49.7% - 74.8%) and bortezomib, cyclophosphamide, and dexamethasone (n = 13, 21%, 95% CI 11.7% - 33.2%). Most patients (n = 48, 77.4%, 95% CI 65% - 87.1%) achieved a very good partial response or better. Eight (n = 8, 13%, 95% CI 5.7% - 23.9%) patients had refractory disease to first line therapy. Forty-six (n = 46, 74%, 95% CI 62% - 85%) patients were referred for HSCT evaluation, n = 16 (26%, 95% CI 15.5% - 38.5%) patients were not. Of the forty-six (n = 46) patients that were referred, n = 44 (96%, 95% CI 85% - 99.5%) patients had a clinical consultation with the transplant team. Of the entire cohort, n = 36 (58%, 95% CI 44.9% - 70.5%) patients underwent stem cell collection and n = 34 (55%, 95% CI 42% - 68%) patients underwent an ASCT after induction therapy. Conclusions: Our study found that more than one third of young patients with newly diagnosed multiple myeloma did not undergo stem cell collection or stem cell transplant. Lack of geographic access to a transplant center may be a contributing factor to the under utilization of this highly effective therapeutic strategy. Further investigation into interventions to improve ASCT referral and completion rates is imperative for improving outcomes for patients in such geographic locations. Disclosures Raj: Amgen: Membership on an entity's Board of Directors or advisory committees; Jazz pharmaceuticals: Speakers Bureau; Glaxo-Smith Kline: Speakers Bureau.

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Hematopoietic Cell Transplant-Composite Risk (HCT-CR) — a Novel Prognostic Model to Predict Transplant Outcomes

Blood ◽

10.1182/blood-2018-99-111639 ◽

2018 ◽

Vol 132 (Supplement 1) ◽

pp. 2141-2141

Author(s):

Piyanuch Kongtim ◽

Simrit Parmar ◽

Denái R. Milton ◽

Jorge M. Ramos Perez ◽

Gabriela Rondon ◽

...

Keyword(s):

Stem Cell ◽

High Risk ◽

Research Funding ◽

Risk Group ◽

High Risk Group ◽

Hematopoietic Cell ◽

Cell Transplant ◽

Hematopoietic Cell Transplant ◽

Composite Risk ◽

Very High

Abstract Introduction Outcomes after allogeneic stem cell transplant (AHSCT) are influenced by both disease and patient related factors. We hypothesized that combining hematopoietic stem cell transplant comorbidity-age index (HCT-CI/Age) and the refined disease risk index (DRI-R) would better predict survival post-transplant and developed a hematopoietic cell Transplant-composite risk (HCT-CR) model, which we tested in a group of patients with acute myeloid leukemia (AML) and myelodysplastic syndrome (MDS) treated at MD Anderson Cancer Center (MDACC). Methods The study included consecutively treated patients, 18 years of age or older, with AML and MDS who received first AHSCT at MDACC between 2005-2016. Donors were HLA-matched related (MRD), HLA-matched unrelated (MUD), 9/10 MUD (MMUD), haploidentical (HAPLO) and 9/10 MRD (MMRD). To develop this model, patients were assigned into 4 groups: 1. Patients with low/intermediate DRI-R and HCT-CI/Age </=3 (low-risk); 2. Patients with low/intermediate DRI-R and HCT-CI/Age >3 (intermediate-risk); 3. Patients with high/very high DRI-R and HCT-CI/Age </=3 (high-risk); and 4. Patients with high/very high DRI-R and HCT-CI/Age >3 (very high-risk). Primary endpoint was 5-year overall survival (OS); other outcomes assess were progression-free survival (PFS), non-relapse mortality (NRM) and relapse rate. The stability of the HCT-CR model was tested by bootstrap resampling. The discrimination power of the HCT-CR model on OS was compared with that of the DRI-R, HCT-CI/Age and cytogenetic risk model by the Harrell C-concordance index. Results The analysis included 942 patients (492 male and 450 female) with a median age of 53 years (range 18-65 years). Cytogenetic data at diagnosis was available in 928 (98.5%) patients and was favorable, intermediate and adverse cytogenetic risk in 63 (7%), 523 (56%) and 342 (37%), respectively. Fifty-five (6%), 399 (43%), 392 (42%) and 82 (9%) patients had low, intermediate, high and very high DRI-R, respectively. The HCT-CI/Age was available in 922 (98%) patients with the median score of 3 (range 0-18). Donor types included MRD (n=377), MUD (n=416), MMUD (n=68), HAPLO (n=73) and MMRD (N=8). Using the HCT-CR model, patients were stratified into 4 risk groups: low (N=272), intermediate (N=168), high (N=284) and very high-risk (N=184), with significantly different survival. The 5-year OS rates for patients in low, intermediate, high and very high-risk group were 57%, 48%, 34%, and 26%, respectively (P<0.001) (Figure 1). The probability of 5-year PFS rates were 55%, 46%, 30% and 23% for these 4 risk groups, respectively (P<0.001). Post-transplant outcomes of all 4 HCR-CR groups are summarized in Table 1. Compared with the low HCT-CR risk group, patients with intermediate, high and very high-risk group had a significantly increased risk of death with HR of 1.42 (95%CI 1.06-1.91; P=0.02), 2.11 (95%CI 1.65-2.70; P<0.001), and 3.02 (95%CI 2.32-3.92; P<0.001), respectively. The significant association between OS and the HCT-CR groups persisted after adjusting for potential confounders with adjusted HR of 1.37 (95%CI 1.02-1.85) for intermediate, 2.08 (95%CI 1.62-2.67) for high and 2.92 (95%CI 2.23-3.82) for very high-risk group when compared with low risk group. The stability of the hematopoietic cell transplant - composite risk model was confirmed in a bootstrap resampling procedure. Among 500 new datasets, on average, patients in intermediate, high and very high-risk group had significantly increased risk of death after transplant when compared with low risk group with HR of 1.39, 2.11 and 2.98, respectively. Results from the concordance test showed that the HCT-CR model provided better discriminative capacity for prediction of OS when compared with DRI-R, HCT-CI/Age and cytogenetic risk group models with C-index of 0.62 versus 0.60, 0.54 and 0.55, respectively. The goodness of fit test showed that the HCT-CR model fit the data significantly better than the other models (P<0.001). Conclusion Combining disease and patient-related factors provides better survival stratification for patients with AML/MDS receiving AHSCT. This novel HCT-CR model will be validated in patients with all diseases undergoing allogeneic hematopoietic stem cell transplantation and results will be presented at the meeting. Disclosures Oran: ASTEX: Research Funding; Celgene: Consultancy, Research Funding; AROG pharmaceuticals: Research Funding. Champlin:Otsuka: Research Funding; Sanofi: Research Funding.

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Acute Kidney Injury in the Modern Era of Allogeneic Hematopoietic Stem Cell Transplantation

Clinical Journal of the American Society of Nephrology ◽

10.2215/cjn.19801220 ◽

2021 ◽

pp. CJN.19801220

Author(s):

Matthew Abramson ◽

Victoria Gutgarts ◽

Junting Zheng ◽

Molly Maloy ◽

Josel Ruiz ◽

...

Keyword(s):

Risk Factors ◽

Acute Kidney Injury ◽

Stem Cell ◽

Hematopoietic Stem Cell Transplantation ◽

Lower Risk ◽

Kidney Injury ◽

Hematopoietic Cell ◽

Cell Transplant ◽

Hematopoietic Cell Transplant ◽

Hematopoietic Stem

Background and objectives Acute kidney injury (AKI) is a major complication of allogeneic hematopoietic stem cell transplantation, increasing risk of non-relapse mortality. AKI etiology is often ambiguous due to heterogeneity of conditioning/graft-versus-host disease (GVHD) regimens. To date, GVHD and calcineurin inhibitor effects on AKI are not well defined. We aimed to describe AKI and assess pre/post-hematopoietic transplant risk factors in a large recent cohort. Design, setting, participants, and measurements We performed a single-center retrospective study of 616 allogeneic hematopoietic cell transplant recipients from 2014-2017. We defined AKI and CKD based on KDIGO criteria and estimated GFR using CKD-EPI equation. We assessed AKI pre/post-hematopoietic transplant risk factors using cause-specific Cox regression and association of AKI with CKD outcomes using Chi-squared test. AKI was treated as a time-dependent variable in relation to non-relapse mortality. Results Incidence of AKI by day-100 was 64%. Exposure to tacrolimus and other nephrotoxins conferred a higher risk of AKI, but tacrolimus levels were not associated with severity. Reduced intensity conditioning carried higher AKI risk compared to myeloablative conditioning. Most stage 3 AKIs were due to ischemic acute tubular necrosis and CNI nephrotoxicity. Kidney replacement therapy was initiated in 21/616 (3%) of whom 9/21 (43%) recovered and 5/21 (24%) survived to hospital discharge. T-cell depleted transplants, higher baseline albumin, and non-Hispanic ethnicity were associated with lower risk of AKI. CKD developed in 21% (73/345) of patients after 12 months. Non-relapse mortality was higher in those with AKI (HR 2.77, 95% CI: 1.8-4.27). Conclusions AKI post-hematopoietic cell transplant remains a major concern. Risk of AKI was higher with exposure to CNIs. T cell depleted hematopoietic cell transplants and higher albumin had lower risk of AKI. Forty-three percent of patients requiring KRT recovered kidney function. Prospective studies are needed to further assess modification of these risk factors.

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How Do We Manage Hematopoietic Cell Transplant during the SARS-CoV-2 Pandemic?

Acta Haematologica ◽

10.1159/000513036 ◽

2021 ◽

pp. 1-7

Author(s):

Haowen Xiao ◽

Yi Luo ◽

Jimin Shi ◽

Aiyun Jin ◽

Mohamad Mohty ◽

...

Keyword(s):

Serum Antibody ◽

Hematopoietic Cell ◽

Antibody Detection ◽

Cell Transplant ◽

Hematopoietic Cell Transplant ◽

Transplant Center ◽

Increased Risk ◽

Unrelated Donors ◽

Minimal Contact ◽

Related Donor

Patients receiving a hematopoietic cell transplant are thought to be at increased risk of infection with severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) and coronavirus infectious disease 2019. Transplant activities at our center continue, and notably, no patient has been infected with SARS-CoV-2. Indeed, social distancing, masking, and education for patients and donors are major pillars of prevention. We recommend potential transplant recipients and donors to be tested for SARS-CoV-2 with qRT-PCR, serum antibody detection, and a lung CT scan pretransplant. If possible, stem cells from HLA-matched unrelated donors by local processing laboratories should be cryopreserved and shipped before initiating pretransplant conditioning. An alternative HLA-haplotype-matched related donor should be identified and evaluated as a backup. The interval immediately after discharge is the time of greatest risk for SARS-CoV-2 infection because of travel and exposure to infected persons. We recommend self-isolation and minimal contact with family members. Nonessential clinic visits should be deferred or substituted with telemedicine consultations if possible. These recommendations are based on our experience at a major transplant center in China. Although some recommendations are evidence based, other recommendations are not and warrant validation in controlled trials.

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