Cost-Effectiveness of Parathyroid Cryopreservation and Autotransplantation.

Importance: Delayed autotransplantation of cryopreserved parathyroid tissue (DACP) is the only surgical treatment for permanent postoperative hypoparathyroidism. Studies suggest that only a small minority of cryopreserved samples are ultimately autotransplanted with highly variable outcomes. For these reasons, many have questioned the economic utility of the process, although, to the authors' knowledge, this has never been formally studied. Objective: To report the clinical outcomes of parathyroid cryopreservation and DACP at a large academic institution and to determine the cost-effectiveness of this treatment. Design, Setting, and Participants: An institutional review board-approved, retrospective review of patients at a single institution who underwent DACP over a 17-year period was conducted with a median follow-up of 48.2 months. A forward-looking cost-utility analysis was then performed to determine the economic utility of cryopreservation/DACP vs usual care (monitoring and supplementation). Patients who had parathyroid tissue in cryopreserved storage between August 2005 to September 2022 at a single-center, academic, quaternary care center were identified. Exposure: Parathyroid cryopreservation and DACP. Main Outcomes and Measures: Graft functionality, clinical outcomes, and cost utility using a willingness-to-pay threshold of $100 000 per quality-adjusted life-year (QALY). Results: A total of 591 patients underwent cryopreservation. Of these, 10 patients (1.7%; mean [SD] age, 45.6 [17.9] years; 6 male [60%]) underwent DACP. A minority of autografts (2 [20%]) were subsequently fully functional, one-half (5 [50%]) were partially functional, and 3 (30%) were not functional. The cost-utility model estimated that at a large academic center over 10 years, the additional cost of 591 patients undergoing cryopreservation and 10 patients undergoing autotransplantation would be $618 791.64 (2022 dollars) and would add 8.75 QALYs, resulting in a cost per marginal QALY of $70 719.04, which is less than the common willingness-to-pay threshold of $100 000/QALY. Conclusions and Relevance: The reimplantation rate of cryopreserved tissue was low (<2%), but when implanted, autografts were at least partially functional 70% of the time. In the first-ever, to the authors' knowledge, formal cost analysis for this treatment, results of the current model suggest that cryopreservation and autotransplantation were cost-effective compared with the usual care for hypoparathyroidism at a large, academic institution. It is recommended that each surgical center consider whether the economic and logistical commitments necessary for cryopreservation are worthwhile for their individual needs.

Impact of Antifungal Prophylaxis Continuation or Discontinuation After Allogeneic Hematopoietic Cell Transplant on the Incidence of Invasive Mold Infection.

Background: Continuing antifungal prophylaxis (AFPx) to prevent invasive mold infections (IMIs) in recipients of allogeneic hematopoietic cell transplantation (alloHCT) after primary hospital discharge from alloHCT admission varies among transplant centers despite recommendations to continue prophylaxis through day +75. Characteristics driving AFPx prescribing at hospital discharge and outcomes are unknown. Methods: In this retrospective analysis, we reviewed patients continuing AFPx vs no AFPx at hospital discharge. We included patients with a hospital stay ≥7 days and ≤40 days. We excluded patients with a history of IMI prior to alloHCT, new IMI during admission, or death prior to discharge. Our primary objective was incidence of probable or proven IMI per the European Organization for Research and Treatment of Cancer and the Mycoses Study Group Education and Research Consortium. Our secondary objectives were nonrelapse mortality at day +100, overall survival at day +100, and characteristics driving AFPx discontinuation at hospital discharge. Results: Of the 430 patients identified, 387 met inclusion criteria. At discharge, 56% (217/387) continued AFPx, and 44% (170/387) had no AFPx. At day +100, 3 probable IMI cases occurred in the group with continued AFPx vs 1 probable IMI case in the no-AFPx group (no proven IMI). Univariate analysis showed no difference in cumulative incidence of probable IMI (P = .440), nonrelapse mortality (P = .072), and overall survival (P = .855) between groups. Multivariable logistic regression demonstrated that patients were less likely to continue AFPx if they had a diagnosis other than acute myeloid leukemia, a length of stay ≤30 days, acute graft-vs-host disease grade 0 or 1, and corticosteroid use ≤5 days. Conclusions: There was no difference in probable IMI at day +100 after alloHCT based on continuing vs discontinuing AFPx at hospital discharge after alloHCT admission supporting a risk-adapted prophylaxis approach.

Comparing transplant outcomes in ALL patients after myeloablative conditioning in mismatch-related or unrelated donor settings.

The optimal myeloablative conditioning regimen for ALL patients undergoing hematopoietic cell transplant (HCT) with an alternative donor is unknown. We analyzed HCT outcomes ALL patients (n = 269) who underwent HCT at our center from 2010 to 2020 in complete remission (CR) after FTBI-etoposide and CNI-based GvHD prophylaxis for matched donor HCT (ETOP-package; n = 196) or FTBI-Fludarabine and post-transplant cyclophosphamide (PTCy)-based prophylaxis for HLA- mismatched (related or unrelated) donors (FLU-package; n = 64). Patients in FLU-package showed a significant delay in engraftment (p < 0.001) and lower cumulative incidence (CI) of any and extensive chronic GVHD (p = 0.009 and 0.001, respectively). At the median follow up of 4.6 years (range 1-12 years); non-relapse mortality, overall or leukemia-free survival and GVHD-free/relapse-free survival were not significantly impacted by the choice of conditioning. However, in patients at CR2 or with measurable residual disease (MRD+), there was a trend towards higher relapse after FLU-package (p = 0.08 and p = 0.07, respectively), while patients at CR1 regardless of MRD status had similar outcomes despite the package/donor type (p = 0.9 and 0.7, respectively). Our data suggests that FLU-package for alternative donors offers comparable outcomes to ETOP-package for matched donor HCT to treat ALL. Disease status and depth of remission at HCT were independent predictors for better outcomes.

Yttrium-90 Anti-CD25-BEAM-Conditioning for Autologous Hematopoietic Cell Transplantation in Peripheral T Cell Lymphoma.

Peripheral T cell lymphomas (PTCL) have a poor prognosis with current treatments. High-dose chemotherapy followed by autologous hematopoietic cell transplant (AHCT) is used as a consolidation strategy after achieving clinical remission with first-line therapy, as well as in chemosensitive relapse if allogeneic transplant is not an option. CD25 is a targetable protein often highly expressed in PTCL. In this phase 1 clinical trial, we tested the addition of beta-emitting 90Y-labeled chimeric anti-CD25 basiliximab (aTac) to BEAM (carmustine, etoposide, cytarabine, melphalan) as conditioning for AHCT in patients with PTCL. Twenty-three AHCT-eligible patients were enrolled, and 20 received therapeutic 90Y-aTac-BEAM AHCT. Radiation doses of 0.4, 0.5 and 0.6 mCi/kg were tested. With no observed dose-limiting toxicities, 0.6 mCi/kg was deemed the recommended phase 2 dose. The most prevalent adverse effect, grade 2 mucositis, was experienced by 80% of patients. As of this report, 6 (30%) of the treated patients had died, 5 due to progressive disease and 1 due to multiple organ failure [median time of death 17 mo (range: 9-21 mo)] post-AHCT. Median follow-up was 24 mo (range: 9-26 mo) overall and 24 mo (range: 13-26 mo) for surviving patients. For patients who received therapeutic 90Y-aTac-BEAM AHCT, the 2-year progression-free and overall survival were 59% (95% CI: 34-77%) and 68% (95% CI: 42-84%), respectively. 90Y-aTac-BEAM appears to be safe as an AHCT conditioning regimen for PTCL, with no increased toxicity over the toxicities historically seen with BEAM alone in this patient population. This trial was registered at www.clinicaltrials.gov as # NCT02342782.

Total Body Irradiation and Fludarabine with Post-Transplant Cyclophosphamide for Mismatched Related or Unrelated Donor HCT.

BACKGROUND: Allogeneic hematopoietic cell transplantation (HCT) remains the only curative treatment for most patients with hematological malignancies. A well-matched donor (related or unrelated) remains as the preferred donor for patients undergoing allogeneic HCT; however, a large number of patients rely on alternative donor choices of mismatched related (haploidentical) or unrelated donors to access HCT. In this retrospective study, we described outcomes of patients who underwent mismatched donor (related or unrelated) HCT with radiation-based MAC regimen in combination with FLU, and PTCy as higher intensity GVHD prophylaxis. We analyzed outcomes based on donor type. METHODS: We retrospectively assessed HCT outcomes in 155 patients who underwent mismatched donor HCT [related/haploidentical vs unrelated (MMUD)] with fractionated-total body irradiation (FTBI) plus fludarabine and post-transplant cyclophosphamide (PTCy) as graft-versus-host disease (GVHD) prophylaxis at City of Hope from 2015 to 2021. Diagnoses included ALL (46.5%), AML (36.1%) and MDS (6.5%). The median age at HCT was 38 years and 126 (81.3%) patients were from ethnic minorities. HCT-CI was ≥3 in 36.1% and 29% had a disease-risk-index (DRI) of high/very high. Donor type was haplo (67.1%) or MMUD (32.9%). RESULTS: At 2-years post-HCT, disease-free survival (DFS) and overall survival (OS) for all subjects were 75.4% and 80.6%, respectively. Donor type did not impact OS [HR=0.72, (95% CI: 0.35,1.49), p=0.37] and DFS [HR=0.78, (95% CI: 0.41,1.48), p=0.44] but younger donors resulted in less grade III-IV acute GVHD (aGVHD, [HR=6.60, (95% CI: 1.80,24.19), p=0.004] and less moderate or severe chronic GVHD [HR=3.53, (95% CI: 1.70,7.34), p<0.001] with a trend toward better survival (p=0.099). MMUD led to significantly faster neutrophil (median 15 vs 16 days, p=0.014) and platelet recovery (median 18 vs 24 days, p=0.029); however, there was no difference in GVHD outcomes between these groups. Non-relapse mortality [HR=0.86, (95% CI: 0.34,2.20), p=0.76] and relapse risk [HR=0.78, 95%CI: (0.33,1.85), p=0.57] were comparable between the two groups. Patient age <40-years and low-intermediate DRI showed a DFS benefit (p=0.004 and 0.029, respectively). High or very High DRI was the only predictor of increased relapse [HR=2.89, 95%CI: (1.32, 6.34), p=0.008]. CONCLUSION: In conclusion, FLU/FTBI with PTCy was well-tolerated in mismatched donor HCT, regardless of relationship with patient, provided promising results, and improved access to HCT for patients without a matched donor especially patients from ethnic minorities and mixed race.

Evaluación urodinámica de la incontinencia urinaria de esfuerzo en el Hospital Guillermo Almenara Irigoyen / Urodinamic evaluation of urinary incontinence at hospital Guillermo Almenara Yrigoyen

Se presentan 15 casos de pacientes con diagnóstico clínico de I.U.E., sometidos a evaluación Urodinámica, en lo que 4 resultados urodinámicos daban diagnóstico de IU mixta, vejiga sensitiva y micción por Rebosamiento. Se hizo evaluación post-operatoria en 4 pacientes y se hizo el valor predicativo entre diagnóstico clínico y urodinámico, encontrándose la importancia de la evaluación urodinámica previa en casos de IUE clínica. Un caso con diagnóstico clínico de vejiga inestable se corroboró por examen urodinámico.