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Allogeneic Blood or Marrow Transplantation with Post-transplantation Cyclophosphamide for Peripheral T-cell Lymphoma: The Importance of Graft Source
Sterling, C. H., Hughes, M. S., Tsai, H. L., Yarkony, K., Fuchs, E. J., Swinnen, L. J., Paul, S., Bolaños-Meade, J., Luznik, L., Imus, P. H., et al
Transplantation and cellular therapy. 2022
Abstract
BACKGROUND The use of post-transplantation cyclophosphamide (PTCy) for graft-versus host-disease (GVHD) prophylaxis has revolutionized allogeneic blood or marrow transplantation (alloBMT), but there is limited published experience in peripheral T-cell lymphoma (PTCL). OBJECTIVES We sought to assess outcomes in patients with PTCL who underwent alloBMT with PTCy. STUDY DESIGN We reviewed the charts of all adult patients aged 18 years or older who underwent alloBMT with non-myeloablative conditioning and PTCy-based GVHD prophylaxis at the Sidney Kimmel Comprehensive Cancer Center between January 2004 and December 2020. RESULTS Sixty-five patients were identified. The median age was 59 years (range, 24-75 years). Lymphoma histology included PTCL-not otherwise specified (n=24), ALK-negative anaplastic large cell lymphoma (n=14), angioimmunoblastic T-cell lymphoma (n=7), enteropathy-associated T-cell lymphoma (n=6), hepatosplenic T-cell lymphoma (n=4), and other (n=10). Eleven patients were in first complete remission (CR1, 17%). The remaining patients were in first partial remission (PR1) or underwent salvage therapy to at least PR prior to transplant. Forty-eight patients received an alloBMT from a haploidentical related donor (74%), 10 from a fully matched donor (15%), and 7 from a mismatched unrelated donor (mMUD, 11%). All patients received fludarabine, cyclophosphamide, and total body irradiation (TBI). The graft source was bone marrow (BM) in 46 patients (71%) and peripheral blood (PB) in 19 patients (29%); all patients in the BM cohort received 200 cGy TBI, and most in the PB cohort (15/19) received 400 cGy TBI. GVHD prophylaxis was PTCy, mycophenolate mofetil, and a calcineurin inhibitor or sirolimus. With a median follow up of 2.8 years (range, 290 days-14.2 years), the 2-year PFS for the entire cohort was 49% (95% confidence interval [CI] 38-64%), and the 2-year OS was 55% (95% CI 44-69%). Outcomes were significantly improved in those receiving PB compared to BM, including 2-year PFS of 79% (95% CI 63-100%) vs. 39% (95% CI 27-56%), 2-year OS of 84% (95% CI 69-100%) vs. 46% (95% CI 33-63%), and 1-year cumulative incidence of (CuI) relapse of 5% (95% CI 0-16%) vs. 33% (95% CI 19-46%), with no difference in GVHD or non-relapse mortality (NRM). CONCLUSIONS AlloBMT with PTCy is safe and well-tolerated in patients with PTCL. Our data suggest increasing TBI dose to 400 cGy and using PB allografts may offer improved disease control and better survival outcomes, though additional studies are needed to confirm these findings.
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Posttransplantation Cyclophosphamide-based Graft versus Host Disease Prophylaxis with Non-myeloablative Conditioning for Blood or Marrow Transplantation for Myelofibrosis
Jain, T., Tsai, H. L., DeZern, A. E., Gondek, L. P., Elmariah, H., Bolaños-Meade, J., Luznik, L., Fuchs, E., Ambinder, R., Gladstone, D. E., et al
Transplantation and cellular therapy. 2022
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Editor's Choice
Abstract
We describe outcomes with posttransplantation cyclophosphamide and non-myeloablative conditioning based allogeneic blood or marrow transplantation for myelofibrosis using matched or mismatched, family or unrelated donors. The conditioning regimen consisted of fludarabine, cyclophosphamide and total body irradiation. Forty-two patients, with a median age of 63 years, were included, of whom 19% had intermediate-1, 60% had intermediate-2, and 21% had high-risk DIPSS-plus disease, and 60% had atleast one high-risk somatic mutation. Over 90% patients engrafted neutrophils at a median of 19.5 days and 7% had graft failure. At 1 and 3-years, respectively, the overall survival was 65% and 60%, relapse-free survival was 65% and 31%, relapse was 5% and 40%, and non-relapse mortality was 30% and 30%. Acute graft versus host disease grade 3-4 was noted in 17% at 1 year and chronic graft versus host disease requiring systemic therapy in 12% patients. Spleen size ≥ 17 cm or prior splenectomy was associated with inferior relapse-free survival (HR 3.50, 95% CI 1.18-10.37, P=0.02) and higher relapse rate (SDHR not calculable, P=0.01). Age > 60 years (SDHR 0.26, 95% CI: 0.08-0.80, P=0.02) and peripheral blood graft (SDHR 0.34, 95% CI 0.11-0.99, P=0.05) was associated with lower risk of relapse. In our limited sample, the presence of a high-risk mutation was not statistically significantly associated with an inferior outcome although ASXL1 was suggestive of inferior survival (SDHR 2.36. 95% CI 0.85-6.6, P=0.09). Overall, this approach shows comparable outcomes as previously reported and underscores the importance of spleen size in evaluation of transplant candidates.
PICO Summary
Population
Patients with high-risk Dynamic International Prognostic Scoring System (DIPSS)-plus myelofibrosis (n=42)
Intervention
Matched or mismatched allogeneic transplantation with non-myeloablative conditioning, and post-transplant cyclophosphamide
Comparison
None
Outcome
Over 90% patients engrafted neutrophils at a median of 19.5 days and 7% had graft failure. At 1 and 3-years, respectively, the overall survival was 65% and 60%, relapse-free survival was 65% and 31%, relapse was 5% and 40%, and non-relapse mortality was 30% and 30%. Acute graft versus host disease grade 3-4 was noted in 17% at 1 year and chronic graft versus host disease requiring systemic therapy in 12% patients. Spleen size ≥ 17 cm or prior splenectomy was associated with inferior relapse-free survival (HR 3.50, 95% CI 1.18-10.37) and higher relapse rate (SDHR not calculable). Age > 60 years (SDHR 0.26, 95% CI: 0.08-0.80) and peripheral blood graft (SDHR 0.34, 95% CI 0.11-0.99) was associated with lower risk of relapse. In our limited sample, the presence of a high-risk mutation was not statistically significantly associated with an inferior outcome although ASXL1 was suggestive of inferior survival (SDHR 2.36. 95% CI 0.85-6.6).
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Allogeneic Blood or Marrow Transplantation with High-Dose Post-transplantation Cyclophosphamide for Acute Lymphoblastic Leukemia in Patients Aged ≥55
Webster, J. A., Reed, M., Tsai, H. L., Ambinder, A., Jain, T., Dezern, A. E., Levis, M. J., Showel, M. M., Prince, G. T., Hourigan, C. S., et al
Transplantation and cellular therapy. 2022
Abstract
BACKGROUND Patients ≥55 years-old with acute lymphoblastic leukemia (ALL) fare poorly with conventional chemotherapy with 5-year overall survival of ∼20%. Tyrosine kinase inhibitors and novel B-cell targeted therapies improve outcomes, but rates of relapse and death in remission remain high. Allogeneic blood or marrow transplantation (AlloBMT) provides an alternative consolidation strategy, and post-transplantation cyclophosphamide (PTCy) facilitates HLA-mismatched transplants with low rates of non-relapse mortality (NRM) and graft-versus-host disease (GVHD). METHODS The transplant database at Johns Hopkins was queried for patients ≥ 55 years old who received alloBMT for ALL using PTCy. FINDINGS The database included 77 such patients. Most received reduced-intensity conditioning (RIC) (88.3%), were in first remission (CR1) (85.7%), and had B-lineage disease (90.9%). For the entire cohort, 5-year relapse-free survival (RFS) and overall survival (OS) were 46% (95% CI 34-57) and 49% (95% CI 37-60). Grade 3-4 acute GVHD occurred in only 3% of patients and chronic GVHD in 13%. In multivariable analysis, myeloablative conditioning led to worse RFS (HR 4.65, p=0.001); while transplant in CR1 (HR 0.30, p=0.004), and transplant for Ph+ ALL vs. T ALL (HR 0.29, p=0.03) improved RFS. Of the 54 patients who received RIC alloBMT in CR1 for B ALL, 5-year RFS and OS were 62% (95% CI 47-74) and 65% (95% CI 51-77), respectively, with a 5-year relapse incidence of 16% (95% CI 7-27) and NRM of 24% (95% CI 13-36). INTERPRETATION RIC AlloBMT with PTCy in CR1 represents a promising consolidation strategy for B ALL patients ≥ 55 years old. FUNDING NIH grants P01 CA225618 and P30 CA06973.
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"Allogeneic blood or marrow transplant with non-myeloablative conditioning and high dose cyclophosphamide-based graft-versus-host disease prophylaxis for secondary central nervous system lymphoma"
Sterling, C. H., Tsai, H. L., Holdhoff, M., Bolaños-Meade, J., Luznik, L., Fuchs, E. J., Huff, C. A., Gocke, C. B., Ali, S. A., Borrello, I. M., et al
Transplantation and cellular therapy. 2021
Abstract
Secondary central nervous system (CNS) lymphoma is a rare and often fatal complication of non-Hodgkin lymphoma (NHL). Treatment options include radiation therapy, high-dose systemic chemotherapy, intrathecal chemotherapy, and high-dose chemotherapy with autologous stem cell rescue, but outcomes remain poor. Allogeneic blood or marrow transplant (alloBMT) is widely used in relapsed/refractory systemic NHL. We sought to understand whether a graft-versus-lymphoma effect could maintain remission in CNS disease. Here we review outcomes in 20 consecutive patients with secondary CNS lymphoma who underwent alloBMT with non-myeloablative conditioning using fludarabine, cyclophosphamide, and 200cGy total-body irradiation. For graft-versus-host disease (GVHD) prophylaxis, all patients received post-transplant cyclophosphamide (PTCy), mycophenolate mofetil, and a calcineurin inhibitor. With a median follow up of 4.1 years, the median overall survival for the entire cohort was not reached. Median progression-free survival was 3.8 years (95% confidence interval [CI] 5.3 months - not reached). The cumulative incidence of relapse was 25% (95% CI 5-45%), and non-relapse mortality was 30% (95% CI 5-54%) at 4 years. Of the 5 patients who relapsed, 2 were CNS only, 1 was systemic only, and 2 were combined CNS / systemic. The use of alloBMT in CNS lymphoma deserves further investigation.
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Nonmyeloablative Allogeneic Transplantation With Post-Transplant Cyclophosphamide for Acute Myeloid Leukemia With IDH Mutations: A Single Center Experience
Ambinder, A., Smith, M., Tsai, H. L., Varadhan, R., DeZern, A., Dalton, W., Gocke, C., Webster, J., Gondek, L., Gojo, I., et al
Clinical lymphoma, myeloma & leukemia. 2021
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Abstract
INTRODUCTION Mutations in the IDH1 or IDH2 genes are detected in approximately 20% of cases of acute myeloid leukemia (AML). Few studies have examined the impact of IDH mutations in AML on allogeneic bone marrow transplant (alloBMT) outcomes. PATIENTS AND METHODS In this single center study, alloBMT outcomes for 61 patients with IDH-mutated (mIDH) AML were compared to those for 146 patients with IDH-wildtype (wtIDH) AML. RESULTS Patients with mIDH AML had a 2-year overall survival (OS) of 85% (95% CI 76%-95%), 2-year relapse free survival (RFS) of 71% (95% CI 59%-85%), 1-year cumulative incidence of relapse (CIR) of 14% (95% CI 5%-23%) and a 1-year cumulative incidence of transplant related mortality (CITRM) of 3% (95% CI 0%-8%). Patients with wtIDH had a 2-year OS of 61% (95% CI 53%-70%), 2-year RFS of 58% (95% CI 50%-67%), 1-year CIR of 27% (95% CI 20%-35%), and a 1-year CITRM of 9% (95% CI 5%-14%). In a univariate analysis cox-proportional hazard model, mIDH was associated with significantly better OS (HR 0.52, 95% CI 0.29-0.96) and a trend toward better RFS (HR 0.60, 95% CI 0.35-1.01). After controlling for donor age, diagnosis, and ELN risk category, mIDH was associated with a nonsignificantly improved OS (HR 0.54, 95% CI 0.29-1.01) and RFS (HR 0.67, 95% CI 0.39-1.15). CONCLUSION Among patients with mIDH AML, patients who received a peritransplant IDH inhibitor had improved OS (P = .03) compared to those who did not, but there was no detectable difference for RFS (P = .29).
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Shortened-duration immunosuppressive therapy after nonmyeloablative, related HLA-haploidentical or unrelated peripheral blood grafts and post-transplantation cyclophosphamide
DeZern, A. E., Elmariah, H., Zahurak, M., Rosner, G. L., Gladstone, D. E., Ali, S. A., Huff, C. A., Swinnen, L. J., Imus, P., Borrello, I., et al
Biology of blood and marrow transplantation : journal of the American Society for Blood and Marrow Transplantation. 2020
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Editor's Choice
Abstract
With post-transplantation cyclophosphamide (PTCy) as graft-versus-host disease (GVHD) prophylaxis, nonmyeloablative (NMA) HLA-haploidentical (haplo) and HLA-matched blood or marrow (BMT) have comparable outcomes. Previous reports showed that discontinuation of immunosuppression (IS) as early as day 60 after infusion of bone marrow (BM) haplo allograft with PTCy is feasible. There are certain diseases in which peripheral blood (PB) may be favored over BM, but, given the higher rates of GVHD with PB, excessive GVHD becomes an increased concern. We present a completed, prospective single-center trial of stopping IS at days 90 and 60 after NMA PB transplantation. Between 12/2015-7/2018, 117 consecutive patients with hematologic malignancies associated with higher rates of graft failure after NMA conditioned BM transplantation and PTCy, received NMA PB allografts on trial. The primary objective was to evaluate the safety and feasibility of reduced-duration IS (from Day 5 through Day 90 in cohort 1 and through Day 60 in cohort 2). Of the 117 patients (median age 64 years, range 22-78), the most common diagnoses were myelodysplastic syndrome (33%), acute myeloid leukemia (with minimal residual disease or arising from antecedent disorder) (32%), myeloproliferative neoplasms (19%) myeloma (9%), and chronic lymphocytic leukemia (7%). Shortened IS was feasible in 75 pts (64%) overall. Ineligibility for shortened IS resulted most commonly from GVHD (17 pts), followed by early relapse (11 pts), non-relapse mortality (NRM) (7 pts), patient/ physician preference (4 pts) or graft failure (3 pts). Of the 57 patients in the D90 cohort, 33 (58%) stopped IS early as planned. Of the 60 patients in the D60 cohort, 42 (70%) stopped IS early as planned. The graft failure rate was 2.6%. After IS cessation, the median time to diagnosis of grade II-IV GVHD was 21 days and 32 days in the day 90 and day 60 cohorts respectively, with almost all cases developing within 40 days. Approximately one-third of these patients did restart IS. All outcome measures were similar in the 2 cohorts and to our historical outcomes with 180 days of IS. The cumulative incidence of grade 3-4 acute GVHD were low at 2 and 7% in D90 and D60, respectively. Severe chronic GVHD was 9% (D90) and 5% (D60) at 2 years. The two year overall survival was 67% for both the D90 and D60 cohorts, The two year progression free survival was 47% for the Day 90 cohort and 52% for the Day 60 cohort with the GVHD-free relapse-free survival less than 35% for both cohorts. These data suggest that reduced-duration IS in pts receiving NMA PB grafts with PTCy is feasible and carries an acceptable safety profile.
PICO Summary
Population
Patients with hematologic malignancies associated with higher rates of graft failure (n=117)
Intervention
Non-myeloablative haploidentical transplant with immunosuppression days 5-90 (D90 cohort, n=57)
Comparison
Non-myeloablative haploidentical transplant, with immunosuppression days 5-60 (D60 cohort, n=60)
Outcome
Shortened immunosuppression (IS) was feasible in 75 pts (64%) overall. Ineligibility for shortened IS resulted most commonly from GVHD (17 pts), followed by early relapse (11 pts), non-relapse mortality (NRM) (7 pts), patient/ physician preference (4 pts) or graft failure (3 pts). Of the 57 patients in the D90 cohort, 33 (58%) stopped IS early as planned. Of the 60 patients in the D60 cohort, 42 (70%) stopped IS early as planned. The graft failure rate was 2.6%. After IS cessation, the median time to diagnosis of grade II-IV GVHD was 21 days and 32 days in the day 90 and day 60 cohorts respectively, with almost all cases developing within 40 days. Approximately one-third of these patients did restart IS. All outcome measures were similar in the 2 cohorts and to our historical outcomes with 180 days of IS. The cumulative incidence of grade 3-4 acute GVHD were low at 2 and 7% in D90 and D60, respectively. Severe chronic GVHD was 9% (D90) and 5% (D60) at 2 years. The two year overall survival was 67% for both the D90 and D60 cohorts, The two year progression free survival was 47% for the Day 90 cohort and 52% for the Day 60 cohort with the GVHD-free relapse-free survival less than 35% for both cohorts.
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Haploidentical BMT for severe aplastic anemia with intensive GVHD prophylaxis including posttransplant cyclophosphamide
DeZern, A. E., Zahurak, M. L., Symons, H. J., Cooke, K. R., Rosner, G. L., Gladstone, D. E., Huff, C. A., Swinnen, L. J., Imus, P., Borrello, I., et al
Blood advances. 2020;4(8):1770-1779
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Abstract
Severe aplastic anemia (SAA) is a stem cell disorder often treated with bone marrow transplantation (BMT) to reconstitute hematopoiesis. Outcomes of related HLA-haploidentical (haplo) donors after reduced-intensity conditioning with intensive graft-versus-host disease (GVHD) prophylaxis including posttransplantation cyclophosphamide are presented here from 37 SAA, 20 relapsed/refractory (R/R), and 17 treatment-naive (TN) SAA patients. Median follow-up is 32 months (90% confidence interval [CI], 29-44). The median age was 25 (range, 4-69) years. The median time to neutrophil recovery was 17 days (range, 15-88). Four of 37 patients (11%) experienced graft failure (GF). There was 1 primary GF of 20 patients in the R/R group and 3 of 17 in the TN group at 200 cGy (1 primary, 2 secondary), but none in the 10 patients who received 400 cGy total body irradiation. Two patients with GF succumbed to infection and 2 were rescued with second haplo BMT. The overall survival for all patients is 94% (90% CI, 88-100) at 1 and 2 years. The cumulative incidence of grade II-IV acute GVHD at day 100 is 11%. The cumulative index of chronic GVHD at 2 years is 8%. Similar results were seen in 10 SAA patients who received the identical nonmyeloablative regimen with posttransplant cyclophosphamide but matched donor transplants. Haplo BMT with posttransplant cyclophosphamide represents a potential cure in SAA, with all 20 R/R currently alive, disease-free, and with no evidence of active GVHD. Extending this approach to TN patients was associated with higher GF rates, but an increase in total body irradiation dose to 400 cGy was associated with durable engraftment without greater early toxicity. Nonmyeloablative haplo BMT in TN SAA could lead to a paradigm shift, such that essentially all patients can proceed quickly to safe, curative BMT. These trials were registered at www.cincialtrials.gov as #NCT02224872) and #NCT02833805.
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Thrombotic Microangiopathy after Post-Transplantation Cyclophosphamide-Based Graft-versus-Host Disease Prophylaxis
Imus, P. H., Tsai, H. L., DeZern, A. E., Jerde, K., Swinnen, L. J., Bolaños-Meade, J., Luznik, L., Fuchs, E. J., Wagner-Johnston, N., Huff, C. A., et al
Biology of blood and marrow transplantation : journal of the American Society for Blood and Marrow Transplantation. 2020
Abstract
Transplant-associated thrombotic microangiopathy (taTMA) is a systemic vascular illness associated with significant morbidity and mortality, resulting from a convergence of risk factors after allogeneic blood or marrow transplantation (alloBMT). The diagnosis of taTMA has been a challenge, but most criteria include an elevated lactate dehydrogenase (LDH), low haptoglobin, and schistocytes on peripheral blood smear. We performed a retrospective review of the 678 consecutive adults who received high-dose post-transplantation cyclophosphamide (PTCy)-based graft-versus-host disease (GVHD) between January 1, 2015, and August 31, 2018. In April 2016, we initiated a monitoring program of weekly LDH and haptoglobin measurements and blood smears when those 2 parameters were both abnormal on all of our adult patients undergoing alloBMT for hematologic malignancies. During the entire period, the 1-year cumulative incidence of taTMA was 1.4% (95% confidence interval, 0.5% to 2.3%). Eight patients were taking tacrolimus at the time of diagnosis, and 1 was not on any immunosuppression. Eight of 9 patients (89%) were hypertensive. Four patients had invasive infections at the time of diagnosis, 4 patients required renal replacement therapy, and 5 of 9 patients were neurologically impaired. Eculizumab was given to 6 patients (0.9%), of whom 2 died and 4 recovered with resolution of end-organ dysfunction. The paucity of events made the determination of risk factors difficult; however, the low incidence of taTMA in this cohort may be related to the limited use of myeloablative conditioning regimens, low incidence of severe GVHD, and use of PTCy. PTCy-based GVHD prophylaxis appears to be associated with a low incidence of severe taTMA.
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Allogeneic transplantation for Ph+ acute lymphoblastic leukemia with posttransplantation cyclophosphamide
Webster, J. A., Luznik, L., Tsai, H. L., Imus, P. H., DeZern, A. E., Pratz, K. W., Levis, M. J., Gojo, I., Showel, M. M., Prince, G., et al
Blood advances. 2020;4(20):5078-5088
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Editor's Choice
Abstract
Allogeneic blood or marrow transplantation (alloBMT) is standard of care for adults with Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph+ ALL) in first complete remission (CR1). The routine pretransplant and posttransplant use of tyrosine kinase inhibitors (TKIs) has dramatically improved outcomes, but the optimal conditioning regimen, donor type, and TKI remain undefined. The bone marrow transplant database at Johns Hopkins was queried for adult patients with de novo Ph+ ALL who received alloBMT using posttransplantation cyclophosphamide (PTCy) as a component of graft-versus-host disease (GVHD) prophylaxis from 2008 to 2018. Among transplants for Ph+ ALL, 69 (85%) were performed in CR1, and 12 (15%) were performed in second or greater remission (CR2+). The majority of transplants (58%) were HLA haploidentical. Nearly all patients (91.4%) initiated TKI posttransplant. For patients in CR1, the 5-year relapse-free survival (RFS) was 66%. The use of nonmyeloablative conditioning, absence of measurable residual disease (MRD) according to flow cytometry at transplant, and the use of dasatinib vs imatinib at diagnosis were associated with improved overall survival (OS) and RFS. Neither donor type nor recipient age ≥60 years affected RFS. When analyzing all transplants, alloBMT in CR1 (vs CR2+) and the absence of pretransplant MRD were associated with improved RFS. Most relapses were associated with the emergence of kinase domain mutations. The cumulative incidence of grade 3 to 4 acute GVHD at 1 year was 9%, and moderate to severe chronic GVHD at 2 years was 8%. Nonmyeloablative alloBMT with PTCy for Ph+ ALL in an MRD-negative CR1 after initial treatment with dasatinib yields favorable outcomes.
PICO Summary
Population
Adults with Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph+ ALL) undergoing allogeneic transplantation (n=76)
Intervention
Myeloablative conditioning in first complete remission (CR1 MAC, n=26); Non-myeloablative conditioning in first complete remission (CR1 NMAC, n=43)
Comparison
Patients in second or subsequent remission (CR2+, n=12)
Outcome
For patients in CR1, the 5-year relapse-free survival (RFS) was 66%. The use of nonmyeloablative conditioning, absence of measurable residual disease (MRD) according to flow cytometry at transplant, and the use of dasatinib vs imatinib at diagnosis were associated with improved overall survival (OS) and RFS. Neither donor type nor recipient age ≥60 years affected RFS. When analyzing all transplants, alloBMT in CR1 (vs CR2+) and the absence of pretransplant MRD were associated with improved RFS. Most relapses were associated with the emergence of kinase domain mutations. The cumulative incidence of grade 3 to 4 acute GVHD at 1 year was 9%, and moderate to severe chronic GVHD at 2 years was 8%.
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10.
Severe cytokine release syndrome after haploidentical peripheral blood transplantation
Imus, P. H., Blackford, A. L., Bettinotti, M., Luznik, L., Fuchs, E. J., Huff, C. A., Gladstone, D. E., Ambinder, R. F., Borrello, I. M., Fuchs, R. J., et al
Biology of blood and marrow transplantation : journal of the American Society for Blood and Marrow Transplantation. 2019
Abstract
INTRODUCTION Inflammatory cytokines released by activated lymphocytes and innate cells in the context of cellular therapy can cause fever, vasodilatation and end organ damage, so-called cytokine release syndrome (CRS). CRS can occur after allogeneic blood or marrow transplantation, but especially after HLA-haploidentical (haplo) peripheral blood transplantation (PBT). We reviewed charts of all patients who underwent haplo PBT between October 1, 2013 and September 1, 2017 and graded CRS. A total of 146 consecutive related haplo PBTs were analyzed. CRS occurred in 130 (89%) of the patients, but most was of mild (Grades 0-2) severity. Severe CRS (Grades 3-5) occurred in 25 patients (17% of PB haploPBT). In this group with severe CRS, 13 had encephalopathy; 12 required hemodialysis, and 11 were intubated. Death from the immediate complications of CRS occurred in 6 patients (24% of the severe CRS group and 4% of the entire haplo PBT cohort). The cumulative probability of non-relapse mortality (NRM) for patients with severe CRS was 38% at 6 months; it was 8% in the 121 out of 146 patients without severe CRS. In conclusion, CRS occurs in nearly 90% of haploidentical peripheral blood stem cell transplants. Older recipients (OR 2.4, 95% CI 0.83-6.75, p=0.11) of haploidentical PBT and those with a history of XRT (OR=3.85, 95% CI 1.32-11.24, p=0.01) have a higher risk of developing severe CRS. Most recipients of haplo PBT develop CRS, but less than 20% experience severe complications. The development of severe CRS significantly increases NRM.