Registration is Open for April's Online Journal Club, Allogeneic Transplant and More

By Content Administrator posted 23 days ago

  

Registration is now open for April’s Online Journal Club. Reserve your seat for this webinar through the following link and please share to all that may be interested: https://attendee.gotowebinar.com/register/6146227515136446467

Dr. Mollie Beck will highlight an in-depth review regarding the article "Tisagenlecleucel in Adult Relapsed or Refractory Diffuse Large B-Cell Lymphoma". The goal of these journal clubs will be to provide education and more in-depth review of literature related to the field of stem cell transplantation and cellular therapy and will be provided a few times a year.

Beck is currently completing her PGY2 Hematology/Oncology Pharmacy Resident at University of Cincinnati Medical Center (UC Health) in Cincinnati, OH. She completed pharmacy school at the University of Cincinnati in 2017.

Thank you and we look forward to your support and attendance!

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

**Battipaglia G, Boumendil A, Labopin M, et al. Unmanipulated haploidentical versus HLA-matched sibling allogeneic hematopoietic stem cell transplantation in relapsed/ refractory acute myeloid leukemia: a retrospective study on behalf of the ALWP of the EBMT. Bone Marrow Transplantation. Feb 2019. [Epub ahead of print] https://www.ncbi.nlm.nih.gov/pubmed/30718798

  • Retrospective review comparing outcomes from HLA-identical (n=1654) sibling or haploidentical (haplo, n=389) donors in relapsed/refractory AML from 2007-2015
  • Haplo HCT were performed more recently (2013 vs 2011, p < 0.01), at longer interval from diagnosis (7 vs 5 months, p < 0.01), and with a reduced intensity conditioning regimen (50% vs 43%, p = 0.03)
  • In multivariate analysis, haplo HCT was associated with lower GVHD/relapse-free survival, inferior leukemia free survival and overall survival, as well as higher non-relapse mortality
  • The worse outcomes in haplo recipients were largely due to a higher rate of infections (41% vs 25%, p < 0.01)
  • For relapsed/refractory AML, MSD remain the gold standard, if possible, due to higher mortality in haplo recipients

Supportive Care

**Johansson JE, Bratel J, Hardling M, et al. Cryotherapy as prophylaxis against oral mucositis after high-dose melphalan and autologous stem cell transplantation for myeloma: a randomised, open-label, phase 3, non-inferiority trial. Bone Marrow Transplantation. Feb 2019. [Epub ahead of print] https://www.ncbi.nlm.nih.gov/pubmed/30718802

  • Prospective, randomized trial in 94 patients who underwent autologous HCT for MM
  • Patients were randomized 1:1 to receive cryotherapy for 7 hours (N=46) or 2 hours (n=48) and oral mucositis was evaluated prospectively
  • 62 patients were males (66%); median age was 59 years (range 34-69); 92 of 94 patients (98%) received melphalan 200 mg/m2
  • There was no significant difference observed between groups in patients who showed grades 3 and 4 toxicity according to WHO scale (2.1 and 4.3% for 2h and 7h, respectively; 95% CI, -0.09-0.049; p=0.98)
  • Two hours of cryotherapy was as effective as 7 hours in terms of protecting against severe oral mucositis and may assist with compliance

**Fujimoto A, Hiramoto N, Yamasaki S, et al. Risk factors and predictive scoring system for post-transplant lymphoproliferative disorder after hematopoietic stem cell transplantation. Biol Blood Marrow Transplant. 2019 Feb. [Epub ahead of print] http://www.ncbi.nlm.nih.gov/pubmed/30794929

  • Retrospective analysis of consecutive patients in the national Japanese transplant registry to assess risk factors for PTLD
  • 64,539 consecutive patients from 1990-2016 were included (40,195 alloHSCT, 24,215 autoHSCT, 129 syngeneic patients) and 299 developed EBV(+) PTLD
  • 2-year post transplant EBV (+) PTLD rates were 0.79% (alloHSCT), 0.78% (syngeneic), and 0.11% (autoHSCT)
  • Predictive risk factors after multivariate analysis included ATG use in conditioning (p<0.001), ATG use for aGVHD (p = 0.01), donors other than HLA-matched related donors (p = 0.001), AA (p<0.001), 2nd or subsequent alloHSCT (p = 0.03), aGVHD ( p<0.001), and more recent HSCT (0.45% before 2009 & 1.24% after 2009, p<0.001)
  • The authors created a 5-point scoring system, based on pre-transplant risk factors, to predict the risk of developing PTLD at the time of alloHSCT: ATG use in conditioning (high-dose: 2 pts, low-dose: 1 pts); donor type (HLA mismatch: 1 pt, unrelated donor: 1 pt, cord blood: 2 pts); AA (1 point)
  • Low risk group (0-1 pts): 0.3% risk of developing PTLD at 2 years post HSCT; intermediate risk group (2 pts): 1.3%; high risk group (3 pts): 4.6%; and very high risk group (4-5 pts): 11.5%
  • The authors concluded that their novel scoring system enables them to predict higher risk patients before HSCT and that further research is warranted to improve the morbidity and mortality of HSCT patients from PTLD

*Fayard A, Daguenet E, Blaise D, et al. Evaluation of infectious complications after haploidentical hematopoietic stem cell transplantation with post-transplant cyclophosphamide following reduced-intensity and myeloablative conditioning: a study on behalf of the Francophone Society of Stem Cell Transplantation and Cellular Therapy (SFGM-TC). Bone Marrow Transplantation. Feb 2019. [Epub ahead of print]  https://www.ncbi.nlm.nih.gov/pubmed/30770870

  • Retrospective review on 381 patients from 30 centers between January 2013 and December 2015 in patients undergoing haplo HCT with post-transplant cyclophosphamide (PTCy)
  • 1058 infectious episodes were noted, affecting 90.3% of the cohort; approximately 41% were bacterial infections and 35% were viral infections, with 48.8% of the viral infections being CMV reactivation
  • Median GVHD relapse-free survival, progression-free survival, and overall survival were 7.1 months, 19.9 months, and 33.5 months, respectively
  • Infections accounted for 45.7% of the HCT-related deaths, with relapsed disease accounting for 34.2% of deaths
  • Haplo HCT with PTCy has an acceptable incidence of infectious complications that does not significantly differ from other HCT platforms

Pediatrics

**Guilcher GMT, Monagel DA, Nettel-Aguirre A, et al. Non-myeloablative matched sibling donor hematopoietic cell transplantation in children and adolescents with sickle cell disease. Biol Blood Marrow Transplant. 2019 Feb.  [Epub ahead of print] http://www.ncbi.nlm.nih.gov/pubmed/30772511

  • Retrospective, single-center cohort analysis of all patients with SCD who underwent MSD HSCT using the NIH NMA protocol (alemtuzumab 0.2mg/kg/day D-7 through D-3 & 300 cGy TBI D-2 and prolonged sirolimus through at least D+365 before weaning)
  • 16 children and adolescents received the NIH NMA protocol followed by GCSF-mobilized PBSC graft
  • All patients were alive at median follow up of 19.5 months post-transplant and, of the 14 patients assessed for SCD pathology, no evidence of recurrent SCD pathologies was found
  • All patients achieved mixed donor-recipient engraftment with no cases of graft failure, sickling crisis, or GVHD observed to date
  • The authors concluded that the NIH MSD protocol can cure children with SCD and a MSD with no documented cases of GVHD and larger prospective clinical trials are required to determine the long-term safety and efficacy of this regimen in children

Abbreviations:

AA: aplastic anemia

aGVHD: acute graft-versus-host disease

alloHSCT: allogeneic hematopoietic stem cell transplant

AML: acute myeloid leukemia

ATG: antithymocyte globulin

autoHSCT: autologous hematopoietic stem cell transplant

CMV: cytomegalovirus

EBV: Epstein-Barr virus

GCSF: granulocyte colony stimulating factor

GVHD: graft-versus-host disease

HCT: Hematopoietic cell transplant

HLA: human leukocyte antigen

MM: multiple myeloma

MSD: matched sibling donor

NMA: nonmyeloablative

PBSC: peripheral blood stem cells

PTLD: post-transplant lymphoproliferative disorder

SCD: sickle cell disease

TBI: total body irradiation

ASBMT Pharmacy SIG Communications Working Committee:

Brandi Anders, Tiene Bauters, Eileen Chen, David Eplin, Katie Gatwood, Jason Jared, Kathryn Maples, Shreya Shah, Ryan Shaw

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