04.26.21

Pharmacy SIG Literature Update: Chemotherapy vs. myeloablative alloHCT in AYA patients

In this month’s Pharmacy SIG Literature Update: Chemotherapy vs. myeloablative alloHCT in AYA patients with ALL, risk-adaptive/preemptive tocilizumab after tisa-cel for pediatric ALL, alloHCT in Hodgkin Disease after PD-1 blockade, and more!

Literature summaries are provided as information only. Please refer to the original published articles for complete details on study methodology, results and discussion.

*** Must read. Landmark publication that affects practice

** Recommend reading. Secondary paper that adds to literature

* Consider reading. Cursory importance to the practice

Allogeneic Transplant

**Aldoss I, Yang D, Al Malki MM, et al. Allogeneic hematopoietic cell transplantation for relapsed and refractory Philadelphia negative B cell ALL in the era of novel salvage therapies. Transplantation and Cellular Therapy.2021 Mar; 27(3):255e1-e9. https://pubmed.ncbi.nlm.nih.gov/33781525/ 

  • Retrospective review comparing post alloHCT outcomes among adults with relapsed/refractory Ph neg. B-ALL (n = 108) who received different salvage therapies as a bridge to alloHCT. All patients achieved morphologic remission prior to alloHCT.
  • The most recent line of therapy prior to alloHCT was chemotherapy (n=45, 42%), blinatumomab (n=43, 40%), inotuzumab (n=14, 13%), and CAR-T (n=6, 6%).
  • Patients who received inotuzumab or CAR-T received a higher number of pre-transplant therapies (3 and 4, respectively) compared to chemotherapy and blinatumomab (2 for both) (p<0.001). Patients who received blinatumomab, inotuzumab, or CAR-T were more likely to be MRD neg. compared to chemotherapy (p=0.005).
  • In a multivariate analysis, conditioning with RIC/NMA regimens (HR 1.23, p = 0.003), having received > 3 lines of therapies prior to HCT (HR 2.66, p < 0.001) and inotuzumab (HR 2.42, p= 0.021) were independently associated with lower RFS. Similar outcomes were observed with 1- year OS.
  • Choice of salvage therapy did not affect NRM at day +100 (p=0.3).
  • 1-year relapse was higher with patients who received inotuzumab (57%) and blinatumomab (19%) compared to chemotherapy (7%) (p<0.001).
  • Rates of aGVHD were not affected by choice of salvage therapy, although chemotherapy was associated with higher incidence of 1-year extensive cGVHD (53%) compared to blinatumomab (33%) or inotuzumab (21%) (p=0.042).
  • Authors concluded that early transplantation after relapse and utilization of myeloablative conditioning when feasible, were key factors associated with improved outcomes after alloHCT in these patients.

**Hilberink JR, Morsink LM, van der Velden WJFM, et al. Pretransplantation MRD in older patients with AML after treatment with decitabine or conventional chemotherapy. Transplantation and Cellular Therapy. 2021 Mar; 27(3):246-252. https://pubmed.ncbi.nlm.nih.gov/33781523/

  • Retrospective review of patients age > 60 years (n = 109) who received decitabine or intensive chemotherapy (7+3) followed by alloHCT at 2 academic centers in the Netherlands
  • 40 patients received decitabine (dose not reported, median number of cycles - 4) and 69 received intensive induction (median number of cycles – 2). No difference in CR/CRi/PR prior to HCT between groups noted (p=0.72).
  • Patients who received decitabine were more likely to be MRD+ compared to intensive chemotherapy (70% vs 37.7%; p<0.001)
  • OS after alloHCT was comparable between both groups.
  • In the chemotherapy arm, the 1-year relapse rate was higher if MRD pos. compared with MRD neg. (50% vs. 9%, respectively). In the decitabine arm, MRD status did not impact 1-year relapse rate
  • A regression analysis confirmed that being MRD pos. increased relapse rate in the chemotherapy arm (sHR 4.81 (1.7-13.64); p=0.0031), but not in the decitabine arm (sHR 0.85 (0.19-3.83); p=0.83).
  • In the chemotherapy arm, MRD pos. patients had a lower 2-year OS survival compared to MRD neg. (57% vs 78%). MRD status did not impact 2-year OS for patients receiving decitabine.
  • The authors concluded that while pre-transplant MRD status has predictive value for patients receiving intensive chemotherapy in AML, this does not hold true for patients receiving decitabine who are over the age of 60 years.

**Wieduwilt MJ, Stock W, Advani A, and et al. Superior survival with pediatric-style chemotherapy compared to myeloablative allogeneic hematopoietic cell transplantation in older adolescents and young adults with Ph-negative acute lymphoblastic leukemia in first complete remission: analysis from CALGB 10403 and the CIBMTR. Leukemia 2021: March 30 online. https://pubmed.ncbi.nlm.nih.gov/33785862/

  • Retrospective study from CIBMTR of Ph-negative ALL patients in CR1 between the ages of 16-39 comparing chemotherapy cohort receiving post-remission chemotherapy on CALGB 10403 (n = 263) to MA alloHCT (MSD, MRD, or URD) cohort (n = 217)
  • Univariate analysis: Both OS and DFS at 3 and 5 years were superior with chemotherapy compared to alloHCT (3-year OS: 77% vs 53%, p<0.001; 5-year OS: 66% vs 47%, p<0.001; 3-year DFS: 68% vs 50%, p<0.001; 5-year DFS: 58% vs 44%, p=0.004). Cumulative relapse rate at 5 years was significantly higher with chemotherapy compared to alloHCT (34% vs 23%, p=0.011).3
  • Multivariate analysis: AlloHCT was associated with inferior OS (HR 2.00, 95% CI 1.5-2.66, p<0.001), inferior DFS (inferior DFS (HR 1.62, 95% CI 1.25–2.12, p<0.001), and increased NRM (HR 5.41, 95% CI 3.23–9.06, p<0.001) compared to chemotherapy. In the early post-remission period (≤15 months after CR1), relapse was more likely with alloHCT (HR 1.78, 95% CI 1.10–2.88, p=0.02) while beyond 15 months after CR1, relapse was more likely in the chemotherapy cohort (HR 0.34, 95% CI 0.19–0.62, p<0.001).
  • Multivariate analysis also showed obesity (BMI ≥30kg/m2 ) was associated with inferior OS (HR 2.17, 95%CI 1.63-2.89, p<0.001), inferior DFS (HR 1.97, 95% CI 1.51–2.57, p<0.001), higher relapse (HR 1.84, 95% CI 1.31–2.59, p<0.001), and higher NRM (HR 2.10, 95% CI 1.37–3.23, p<0.001)
  • The authors concluded that for AYA ALL patients in CR1, post-remission therapy with pediatricstyle chemotherapy is superior to MA alloHCT for OS, DFS, and NRM. Obesity in AYAs with ALL warrants further investigation as shown in this study to negatively impact survival.

**Merryman RW, Castagna L, Giordano L, and et al. Allogeneic transplantation after PD-1 blockade for classic Hodgkin lymphoma. Leukemia 2021: March 03 online. https://pubmed.ncbi.nlm.nih.gov/33658659/

  • International retrospective cohort study evaluating alloHCT outcomes including associations with transplant timing and methods, especially the use of PTCy, in 209 classical HL patients who underwent alloHCT after PD-1 blockade, with or without intervening therapy
  • With a median follow-up of 24 months, the 2-year GRFS, PFS, and OS were 47% (95% CI 40–54), 69% (95% CI 61–75), and 82% (95% 76–87), respectively. Based on multivariate analysis, PTCy was generally associated with improved outcomes regardless of donor type whereas the combination of PTCy with ATG was linked with inferior 2-year GRFS (HR 6.5, p=0.001), PFS (HR 17.4, p<0.0001), and OS (HR 27.5, p<0.0001).
  • For patients in CR at the time of alloHCT, 2-year PFS was similar regardless of pre-alloHCT therapy (82% for patients who underwent alloHCT immediately after PD-1 vs 72% after intervening salvage therapy, p=0.184). Both univariate and multivariate analyses showed that patients who proceeded directly to alloHCT after PD-1 had lower cumulative RI than those who had intervening salvage therapy.
  • Multivariate analysis showed that time from the last dose of PD-1 mAb to alloHCT was the only significant predictor of acute GVHD; an interval of >80 days from PD-1 to alloHCT (the median value in this cohort) was associated with a lower risk of grade 2–4 (HR 0.4, p=0.04) and grade 3– 4 (HR 0.4, p=0.01) aGVHD.
  • PTCy use was not associated with significant reduction in grade 2-4 (33% vs 41%; HR 0.8, p=0.22) or grade 3-4 aGVHD (14% vs 18%; HR 0.7, p=0.34), although it was associated with a reduced risk of cGVHD for both haplo/PTCy (HR 0.5, p=0.026) and non-haplo/PTCy patients (HR 0.2, p=0.011) compared to non-haplo/no PTCy patients.
  • The authors concluded that alloHCT after PD-1 blockade is associated with favorable outcomes. PTCy-based GVHD prophylaxis was associated with significantly improved PFS and GRFS, and this strategy should be considered for all patients undergoing alloHCT after PD-1 blockade.

*Epstein-Peterson ZD, Ganesan N, Barker JN, and et al. Outcomes of adult T-cell leukemia/lymphoma with allogeneic stem cell transplantation: single-institution experience. Leukemia Lymphoma 2021: online March 29. https://pubmed.ncbi.nlm.nih.gov/33779474/

  • A single-center retrospective study evaluating alloHCT outcomes on 17 non-Japanese patients with human T-lymphotropic virus type 1 (HTLV-1)-associated adult T-cell leukemia/lymphoma who underwent alloHCT between 2007 through 2019
  • As of August 2020, 8 patients (47%) were alive without disease, 2 patients were alive receiving treatment following relapse, 4 patients were deceased following disease relapse, 2 patients deceased from transplant-related complications, and 1 deceased from other causes.
  • With a median follow-up of 46 months, median PFS was 76 months (95% CI 5-83) and median OS has not been reached. Evidence shows a trend towards improved PFS for TBI >400cGy-based conditioning compared with <400cGy but was not statistically significant (p=0.06).
  • At 6 months, cumulative RI was 24% and TRM was 12%, and neither occurred between months 6 to 12. Ten patients (59%) developed aGVHD at a median onset of 38 days. Four patients (24%) developed cGVHD at a median time of onset of 234 days.
  • The authors concluded that our data reinforce the utility of alloHCT in ATLL in non-Japanese patients and the importance of achieving disease remission (CR to near CR/low-level disease) to allow for this approach.

*Craddock C, Jackson A, Loke, J, et al. Augmented reduced-intensity regimen does not improve postallogeneic transplant outcomes in acute myeloid leukemia. J Clin Oncol. 2021;39:768-79. https://pubmed.ncbi.nlm.nih.gov/33373276/

  • A phase II, open-label, multicenter, randomized trial comparing an investigators choice of 3 control regimens (Flu/Bu/ATG, Flu/Mel/alemtuzumab, or Flu/Bu/Alemtuzumab) or the novel FLAMSA-Bu regimen (fludarabine, cytarabine 2 g/m2 once daily x 4 days, amsacrine 100 mg/m2 once daily x 4 days, busulfan 11.2 mg/kg, ATG 5 mg/kg over 3 days); doses were reduced in patients with age > 60; n= 244 (high risk AML= 164, MDS = 80)
  • No difference noted in 2-year OS (HR 1.05, 85% CI, 0.80 to 1.38; P = 0.81) or clinical incidence of relapse (HR 0.94, 95%CI, 0.60 to 1.46; p=0.81).
  • Pre-transplant minimal residual disease detected by flow cytometry predicted increased 2-year cumulative incidence of relapse, 41% vs. 20% (P=0.01).
  • There were no significant differences in 1-year TRM (HR 1.20, 95% CI, 0.68 to 2.13; P=0.53), cumulative incidence of day aGVHD at day +100 (grades II-IV, 10.1% v 8.3%, P=0.93; grade III-IV, 1.7% vs 5.8%, P=0.23), or cumulative incidence of cGVHD at 1 year (25.2% vs 19.2%, p=0.53) between the control arm and FLAMSA-Bu arms, respectively.
  • Data presented here differs from BMT CTN 0901 which found significant differences in MRDpositive patients receiving RIC but not MAC, although the authors note that CTN 0901 trial used next-generation sequencing vs. flow cytometry testing for MRD

*Pierini A, Ruggeri L, Carotti A, et al. Haploidentical age-adapted myeloablative transplant and regulatory and effector T cells for acute myeloid leukemia. Blood. 2021;5(5):1199-1208. https://pubmed.ncbi.nlm.nih.gov/33646302/

  • Single-center, prospective study evaluating a novel haplo HCT protocol in 51 patients with AML utilizing an age-adapted irradiation protocol, Treg and Tcon infusions, pre-progenitor cell infusion, and no pharmacologic GVHD prophylaxis post-HCT. Patients received a total of 13.5 Gy (in 9 fractions) of TBI (age < 50 years) or TMLI (age 51-65 years), followed by thiotepa (5-10 mg/kg) + fludarabine (150-200 mg/m2 ) + cyclophosphamide (30 mg/kg/day). Tregs were infused on Day -4 (2 x 106/kg) followed by Tcons on Day -1 (1 x 106/kg), then CD34+ positively purified hematopoietic progenitor cells on Day 0.
  • 10 patients (20%) experienced NRM, with no difference noted between the TBI and TMLI groups. One patient died before engraftment at Day +8, but all others achieved full donor-type engraftment. 2 of the 51 patients (4%) relapsed at 5 and 72 months. Both were MRD+ at the time of transplant.
  • 15 patients (33%) developed grade >2 aGVHD (12 developed to grade 3-4) at a median of 41 days. Only 5 (33%) of the GVHD patients were steroid-refractory, with only 3 patients (20%) remaining on immunosuppression at follow-up. 4 patients (8%) developed mild cGVHD, and 1 patient (2%) developed severe cGVHD.
  • At a median follow-up of 29 months, OS was 77% with cGVHD/RFS of 48% and moderate/severe survival of 75%
  • Authors conclude that an age-adapted MAC regimen with Treg/Tcon adoptive immunotherapy provided remarkably low leukemia and cGVHD rates, with unprecedented cGVHD/RFS

Autologous Transplant

*Khan N, Lindner S, Gomes ALC, et al. Fecal microbiota diversity disruption and clinical outcomes after auto-HCT: a multicenter observational study. Blood. 2021;137(11):1527-35. https://pubmed.ncbi.nlm.nih.gov/33512409/

  • Prospective, observational study conducted at two transplant centers in the U.S. analyzing 1161 fecal samples collected from 534 adult autoHCT recipients with lymphoma, myeloma, and amyloidosis. Included patients received MAC chemotherapy and had at least 1 evaluable stool sample collected between Day -30 and + 100 from their first autoHCT
  • A decrease in fecal diversity from Day -10 to +30 was observed at both centers (p<0.01)using Diversity nadir was noted at +14 and +17 for the two transplant centers, and increased after nadir until Day +100.
  • Patients presenting for autoHCT demonstrated lower fecal diversity than healthy volunteers (Simpson score 9.39 vs. 15.87, p=0.003), indicating that autoHCT recipients start with a lower fecal diversity than normal, and incur additional loss during HCT
  • All patients with an evaluable stool sample in the peri-neutrophil engraftment period (+9 to +16) were analyzed for OS and PFS. Patients with greater fecal diversity had a decreased risk of progression or death after adjusting for disease type and status (HR 0.6, p=0.006).
  • Authors conclude that the health of the intestinal microbiota may impact PFS and OS after autoHCT and requires further investigation

Graft-versus-Host Disease

*Maas-Bauer K, Kiote-Schmidt C, Bertz H, et al. Ruxolitinib-ECP combination treatment for refractory severe chronic graft-versus-host disease Bone Marrow Trasnplant.2021;56:909-916. https://pubmed.ncbi.nlm.nih.gov/33203951/

  • Steroid-refractory chronic GVHD has poor outcomes with few treatment options including ruxolitinib, ECP, ibrutinib, and mTOR inhibitors. This is a retrospective analysis of ruxolitinib and ECP when given in combination; outcomes are reported in reference to when these treatments were given simultaneously.
  • Ruxolitinib was given at 5 or 10 mg twice daily and patients were also treated with ECP on 2 consecutive days every 2-4 weeks. Complete response was defined as the absence of any cGVHD symptoms, and PR was defined as at least 50% reduction of all systemic immunosuppressive therapy or an improvement of one affected organ of at least 50%.
  • Results for 23 patients were analyzedafter a median duration of cGVHD of 2 months prior to treatment start. The overall response rate was 74% including 9% CR. The median time to response after treatment start was 5 weeks and reduction of steroid dose occurred in 76% of patients. New cytopenias occurred in 22% of patients and CMV reactivation occurred in 26%.
  • The authors conclude thatthe combination of ruxolitinib and ECP is safe and has synergistic activity in SR-cGVHD. The authors highlight that there were no relapses in this study and that this combination may not diminish GVL effects. These results should be tested in a future prospective controlled trial.

*Jurdi NE, Rayes A, MacMillan ML, et al. Steroid-dependent acute GVHD after allogeneic hematopoietic cell transplantation: risk factors and clinical outcomes. Blood Adv. 2021; 5(5):1352-9. https://pubmed.ncbi.nlm.nih.gov/33656537/

  • Retrospective, single-institution, cohort study to assess the incidence, risk factors, and clinical outcomes of patients with aGVHD who were SS, SD, or SR after initial steroid therapy. Patients were started on 2 mg/kg/day of prednisone equivalent and response was determined by comparing the initial aGVHD stage and day 28 after initiation of steroids.
  • Of 1143 consecutive adult and pediatric alloHCT recipients, 34% developed aGVHD, with 10% being SS, 9% SD, and 14% SR. 78% of patients had standard-risk disease at onset, and 22% had high-risk disease. 11% had grade 1 disease at onset, 52% with grade 2, 31% with grade 3, and 6% with grade 4. High-risk GVHD was more common in the SR group (56%) compared to 20% in the SS and 24% in the SD groups.
  • 2-year OS was similar in the SS and SD groups (68% vs 68%, p<0.01), and lowest in the SR group (88%, p<0.01). 2-year OS in the pediatric SS, SD, and SR groups was 88%, 70%, and 43%, respectively (p<0.01).
  • Amongst patients with malignant disease, NRM was 40% in the SR group and significantly higher than the SS and SD groups (19% and 20%, respectively, p<0.01). Relapse risk was similar in all three groups. Causes of death in SR group were most often attributed to aGVHD (43%), but not in the SS and SD groups (6% and 13%, respectively). Disease relapse was the primary cause of death in the SS group (66%), but not the SD and SR groups (47% and 23%, respectively).
  • Cumulative incidence of cGVHD was highest in the SD group, followed by the SR and SS groups (46%, 41%, and 29%, p<0.01).
  • Authors conclude that SD was associated with higher risks of subsequent cGVHD, but without increased risk of 2-year OS, NRM, or relapse as compared to the SS group. Redefining aGVHD into these 3 response groups should be used to examine the impact of alternative GVHD therapies.

Cellular Therapy

*Abramson JS, Siddiqi T, Garcia J, et al. Cytokine release syndrome and neurological event costs in lisocabtagene maraleucel-treated patients in the TRANSCEND NHL 001 trial. Blood Adv. 2021;5(6):1695- 1705. https://pubmed.ncbi.nlm.nih.gov/33720336/

  • Retrospective analysis of patient from TRANSCEND observing HCRU associated with toxicity management of prospectively identified CRS and/or neurotoxicity. Primary endpoint was the cost of CRS and NE management (aggregated to estimate the total cost for an individual patient) and included any CRS or neurotoxicity episode up until 90 days after infusion.
  • 127 of 268 (47.4%) of patients experienced CRS and/or neurotoxicity. Of these, 47 patients (37.0%) had CRS only, 14 (11.0%) had neurotoxicity only, and 66 (52.0%) had concurrent CRS with neurotoxicity; and 98 (77.2%) experienced only a grade 1 or 2 event.
  • Median costs ranged from $7,517 to $61,228 for CRS only, $1,930 to $17,609 for neurotoxicity only, and $33,219 to $177,343 for concurrent CRS and neurotoxicity. Grade 1 costs for CRS and neurotoxicity were $7,517 and $1,930, respectively; grade 2 costs were $18,013 and $17,074, respectively; and grade 3 costs were $61,228 and $17,609, respectively. Management of grade >3 events resulted in 193.3% more costs vs grade <2 events.
  • Median total costs of all-grade CRS and/or neurotoxicity who received liso-cel in the outpatient setting was $14,566 compared to $26,186 in the inpatient setting. Facility costs comprised 79.7% of total management costs across all patients, and drug expenditures only accounting for 9.4% of all costs (though costs for liso-cel and lymphodepletion were not included).
  • Authors conclude that a CAR T-cell therapy that is associated with a low incidence of grade >3 events, a low rate of transfer to the ICU, and a safety profile that supports outpatient administration would further reduce strain on the healthcare system.

*Sakemura R, Cox MJ, Hefazi M, and et al. Resistance to CART cell therapy: lessons learned from the treatment of hematological malignancies. Leukemia Lymphoma 2021: online March 08. https://pubmed.ncbi.nlm.nih.gov/33682608/

  • This review discusses lessons learned from failure and resistance to CART cells in the treatment of B cell malignancies. It highlights current approaches and future perspectives to overcome resistance, improve CART cell activity in hematological malignancies, and potentially expand CART applications to solid tumors.
  • Mechanisms of resistance are classified in 3 groups:
    • Tumor-induced mechanisms of resistance
    • Intrinsic T cell defects and dysfunction
    • Tumor-microenvironment (TME)-induced T cell inhibition
  • The authors concluded that development of novel strategies in this decade include:
    • Dual targeting CART cells to prevent antigen loss relapse (e.g. dual CART19/CART22 cell therapy)
    • Combination of CART cells with checkpoint blockade or immunomodulatory agents to re-invigorate CART response (e.g. combination of CART19 with PD-1 blockade)
    • Combination of CART cells with small molecules or monoclonal antibodies to modulate the TME (e.g. combination of CART19 with GM-CSF neutralizing antibodies)
    • Genetically engineered CART to resist exhaustion or to target different components of the TME (e.g. PD-1 k/o CART19 cells)

Pediatrics

*Kaduke S, Myers RM, Li Y, et al. Risk-adapted preemptive tocilizumab to prevent severe cytokine release syndrome after CTL019 for pediatric B-cell acute lymphoblastic leukemia: a prospective clinical trial. J Clin Oncol. 2021;39:920-930. https://pubmed.ncbi.nlm.nih.gov/33417474/

  • Prospective trial to determine the effectiveness of risk-adapted preemptive tocilizumab administration in preventing severe cytokine release syndrome (CRS) after CTL019/tisa-cel in children and young adults with CD19-positive relapsed or refractory B-cell ALL (n=70)
  • Patients assigned to high- (≥40%) or low- (<40%) tumor burden cohorts (HTBC, n=15 and LTBC, n=55). HTBC patients received a single dose of tocilizumab (8-12 mg/kg) after development of high, persistent fevers; LTBC patients received standard CRS management.
  • Incidence of grade 4 CRS (Penn scale) was 27% vs 3.6% in the HTBC and LTBC groups, respectively.
  • Best overall response rate was 87% in the HTBC and 100% in the LTBC. EFS and OS were worse in the HTBC (p = 0.004, p < 0.001, respectively).
  • Initial CTL019 expansion was greater in the HTBC than the LTBC (P<0.001), but persistence was not different (p = 0.73).
  • In the post hoc analysis comparison, grade 4 CRS was observed in 27% in the preemptive tocilizumab vs 50% of patients in the prior phase I CTL019 patient cohort (p =0.18).
  • Authors conclude that risk-adapted preemptive tocilizumab administration resulted in a decrease in the expected incidence of grade 4 CRS, without adversely impacting the antitumor efficacy or safety of tisa-cel.

Abbreviations:

aGVHD: acute graft-versus-host disease

ALL: acute lymphoblastic leukemia

AML: acute myeloid leukemia

alloHCT: allogeneic hematopoietic cell transplantation

autoHCT: autologous hematopoietic cell transplantation

AYA: adolescents and young adults

BMI: body mass index

Bu: busulfan

CAR: chimeric antigen receptor

cGVHD: chronic graft-versus-host disease

cGy: centigray

CR: complete remission9

CRi: complete remission with incomplete count recovery

CRS: cytokine release syndrome

DFS: disease-free survival

Flu: fludarabine

GM-CSF: Granulocyte-macrophage colony-stimulating factor

GVHD: graft-versus-host disease

haplo HCT: haploidentical hematopoietic cell transplantation

HCRU: health care resource utilization

HCT: hematopoietic cell transplantation

HTBC: high tumor burden cohort

ICU: intensive care unit

liso-cel: lisocabtagene maraleucel

LTBC: low tumor burden cohort

MAC: myeloablative conditioning

Mel: melphalan

MRD: minimal residual disease OR matched related donor

MSD: matched sibling donor

NE: neurologic event

NMA: nonmyeloablative

NRM: non-relapse mortality

OS: overall survival

PD-1: Programmed cell death protein 1

PFS: progression-free survival

PR: partial response/remission

RFS: relapse-free survival

RIC: reduced-intensity conditioning

SD: steroid-dependent

SR: steroid-refractory

SS: steroid-sensitive

TBI: total body irradiation

Tcon: conventional T-cells

Tisa-cel: tisagenlecleucel

TMLI:total marrow and lymphoid irradiation

Treg : regulatory T-cells

URD: unrelated donor

ASTCT Pharmacy SIG Research Working Committee: Jennifer Collins, Kelly Gaffney, Katie Gatwood, Arpita Gandhi, Jitesh Kawedia, Binni Kunvarjee, Andrew Lin, Dennis Marjoncu, Jonathan Ptachcinski, Julianna Roddy, Lily Yan

 

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