Review of conditioning regimens for haplo-identical donor transplants using post-transplant cyclophosphamide in recipients of G-CSF mobilised peripheral stem cell

Abstract High dose chemotherapy preceding stem cell transplant carries considerable risk of organ toxicity. Hepatic toxicity is one of the major causes of morbidity post transplant. The etiology is multi-factorial, with the common culprits being graft versus host disease as well as the agents used as part of the conditioning regimen. Evidence of pre-existing mild hepatic insufficiency demands an even more cautious approach while selecting a conditioning regimen prior to stem cell transplant. We analyzed the effect of various myeloablative conditioning regimens on post transplant liver function tests (LFT). CEP (cyclophosphamide, etoposide and cisplatin), BuCy (busulfan and cyclophosphamide), BEAM (carmustine, etoposide, cytarabine and melphalan) and Cy/TBI (cyclophosphamide with total body irradiation) were the four most commonly used regimens for autologous stem cell transplant (auto-SCT) at our center. A total of 404 patients were treated with CEP (210), BuCy (76), CyTBI (71) or BEAM (47) from 1988 to 2013. The majority of the patients underwent an auto-SCT for lymphoma (218 non-Hodgkin lymphoma, 98 Hodgkin’s lymphoma), while 67 transplant patients had leukemia. Patient age ranged from 17 to 73 years at the time of transplant, and the sex distribution revealed a male:female ratio of 1.5:1. We looked at the incidence of total bilirubin greater than 2 mg/dl, alkaline phosphatase greater than upper limit of normal, ALT greater than 126 U/L and AST greater than 82 U/L. The outcome of univariate analysis using chi-square test demonstrated statistically significant inter-group variability for three of the LFTs. CyTBI had the lowest incidence of hepatic insufficiency. Further analysis comparing CyTBI to the other three regimens, confirmed a highly significant statistical difference (p<0.01 by two-sided Fisher’s Exact test, see table below) in elevation of bilirubin, alkaline phosphatase as well as both the transaminases, favoring Cy/TBI as the safer regimen. This is an interesting finding given the common perception that TBI-based regimens are more toxic.CEP, BuCy and BEAMCy/TBIaffected/total (%)affected/total (%)p-valueTotal Bilirubin (≥ 2 mg/dl)27/263 (10.2 %)0/59 (0 %)0.007Alkaline Phosphatase (≥ upper limit of normal)97/262 (37 %)8/58 (13.7 %)0.0005ALT (≥ 126 U/L)39/263 (14.8 %)0/59 (0 %)0.0002AST (≥ 82 U/L)44/264 (16.7 %)2/59 (3.3 %)0.0065 Disclosures: No relevant conflicts of interest to declare.

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Reduced Intensity Conditioning Regimens in Autologous Hematopoietic Stem Cell Transplantation for Multiple Sclerosis patients.

Blood ◽

10.1182/blood.v114.22.2317.2317 ◽

2009 ◽

Vol 114 (22) ◽

pp. 2317-2317

Author(s):

Andrei A. Novik ◽

Alexey N. Kuznetsov ◽

Vladimir Y Melnichenko ◽

Denis A Fedorenko ◽

Andrey Kartashov ◽

...

Keyword(s):

Multiple Sclerosis ◽

Stem Cell ◽

Hematopoietic Stem Cell Transplantation ◽

Stem Cell Transplantation ◽

Reduced Intensity Conditioning ◽

Hematopoietic Stem ◽

Post Transplant ◽

Conditioning Regimens ◽

Reduced Intensity

Abstract Abstract 2317 Poster Board II-294 High-dose immunosuppressive therapy with autologous hematopoietic stem cell transplantation (AHSCT) offers promising results in the treatment of multiple sclerosis (MS) patients. Reduced intensity conditioning regimens (RIC-AHSCT) is a way to improve the balance between benefits and side effects of this treatment approach. The goal of our research was to study the safety and treatment outcomes of RIC-AHSCT in patients with various types of MS. One hundred thirty six patients with MS: secondary progressive (SP) – 48 patients, primary progressive (PP) – 23, progressive-relapsing (PR) – 5 and relapsing-remitting (RR) – 60, were included in this study (mean age - 33.0, range: 17-54; male/female – 57/79). The conditioning regimen included reduced or modified BEAM. The median EDSS at base-line was 4.0 (range 1.5 – 8.5). The median follow-up duration was 17.2 months (range 6 – 35 months). Neurological evaluation was performed at baseline, at discharge, at 3, 6, 9, 12 months, and every 6 months thereafter AHSCT. MRI examinations were performed at baseline, at 6, 12 months, and at the end of follow-up. No transplant-related deaths were observed. Transplantation procedure was well tolerated by the patients with no unpredictable severe adverse events. Among 91 patients included in the efficacy analysis 44 patients (48.5%) experienced clinical stabilization; 46 (50.5%) – improvement, and 1 patient (1%) – progression 6 months post-transplant. Among 31 SPMS patients 16 improved and 15 – stabilized; among 15 PPMS patients 7 improved, 7 – stabilized, and one progressed (PPMS); among 42 RRMS patients 20 improved and 22 – stabilized. In 12 months post-transplant 66% patients improved and 32% – stabilized. One patient (SPMS) progressed after 6 months stabilization. Relapses within the first year post-transplant were registered in 3 patients (2 SPMS; 1 PRMS). No active, new or enlarging lesions on MRI were registered in patients without disease progression. In conclusion, this study provides ample evidence in support of safety and efficacy of reduced intensity conditioning AHSCT in patients with various types of MS. The collection of long-term follow-up data is worthwhile to verify these findings. The rationale of evolution from myeloablative to non-myeloablative transplant regimens should be confirmed by the further studies. Disclosures: No relevant conflicts of interest to declare.

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The Outcome of Hematopoietic Stem Cell Transplantation in Pediatric Patients with Hemophagocytic Lymphohistiocytosis in Korea.

Blood ◽

10.1182/blood.v110.11.5073.5073 ◽

2007 ◽

Vol 110 (11) ◽

pp. 5073-5073

Author(s):

Jae Hee Lee ◽

Hoi Soo Yoon ◽

Joon Sup Song ◽

Ho Jun Im ◽

Hyung Nam Moon ◽

...

Keyword(s):

Stem Cell ◽

Hematopoietic Stem Cell Transplantation ◽

Stem Cell Transplantation ◽

Hemophagocytic Lymphohistiocytosis ◽

Graft Failure ◽

Pediatric Patients ◽

Hematopoietic Stem ◽

Post Transplant ◽

Cell Sources ◽

Conditioning Regimens

Abstract Objective: Chemoimmunotherapy based treatments improved the survival of patients with hemophagocytic lymphohistiocytosis (HLH), but the outcome is still unsatisfactory. We analyzed the outcome of pediatric patients with HLH after hematopoietic stem cell transplantation (HSCT) in a nation-wide HLH registry. Methods: Retrospective nation-wide data recruitment for HLH pediatric patients diagnosed between 1996 and 2005 was carried out by Histiocytosis Working Party of the KSH and KSPHO. Sixteen patients who received HSCT among enrolled 129 pediatric patients with HLH were analyzed for transplant related variables and events. Results: The probability of 3-year survival after HSCT was 81.2% with median follow-up of 27.5 months compared to the 35.2% for patients who were treated with chemoimmunotherapy only (P=0.03). The reasons for HSCT were active disease at 2 months after treatment (n=8), relapsed disease (n=5), and familial HLH (n=3). Eight patients received transplants from matched unrelated donors, 5 from matched siblings and 3 using unrelated cord blood units. Stem cell sources were bone marrow for all the 13 allogeneic transplants other than 3 cord blood transplants. Conditioning regimens were busulphan, cytoxan, and VP-16 with (5) or without (7) antithymocyte globulin (ATG) in 12 patients, fludarabin and melphalan in 3, and other regimen in 1. Graft-versus-host disease (GVHD) prophylaxis consisted of cyclosporine (CSA) + MTX in 11 patients, CSA +MMF in 2, and others in 2. Twelve patients are alive in complete remission state, 3 patients died of infection and graft failure at early post-transplant period, and 1 patient relapsed at post-transplant 30 days. The relapsed patient developed tuberculous encephalitis after retreatment with chemoimmunotherapy, and alive with supportive care. After HSCT, acute GVHD developed in 5 patients, infection in 5, veno-occlusive disease (VOD) in 2, graft failure in 2, and post-transplant lymphoproliferative disease (PTLD) in 1. Acute lymphoblastic leukemia developed in 1 patient about 2 years after HSCT. Variables such as age at diagnosis, etiology of HLH (familial or secondary), central nervous system (CNS) involvement, disease state after 8 weeks of initial treatment, conditioning regimens, and stem cell sources were not associated with significant difference with regard to 3-year overall survival after HSCT. Conclusion: HSCT revealed excellent outcome for patients with familial, relapsed, or severe and persistent secondary HLH in Korean nation-wide HLH registry.

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Post-transplant lymphoproliferative disorder-related admissions in the United States.

Journal of Clinical Oncology ◽

10.1200/jco.2019.37.15_suppl.e19071 ◽

2019 ◽

Vol 37 (15_suppl) ◽

pp. e19071-e19071

Author(s):

Arlene Yu ◽

Prakash Acharya ◽

Seema Singh ◽

Momcilo Durdevic ◽

Andreea Stan ◽

...

Keyword(s):

United States ◽

Bone Marrow ◽

Stem Cell ◽

Hospital Admissions ◽

Organ Transplant ◽

The United States ◽

Solid Organ Transplant ◽

Solid Organ ◽

Post Transplant ◽

Peripheral Stem Cell

e19071 Background: Post-transplant lymphoproliferative disorders (PTLD) is an immunosuppression-related malignancy complicating solid organ transplant (SOT) and non-solid organ transplant (NSOT) (peripheral stem cell and bone marrow transplant). The epidemiology of PTLD-related hospital admissions (PRA) is unclear. The objective of our study is to describe the trend and outcomes of PRA in the United States. Methods: A descriptive, retrospective study was conducted using the National Inpatient Sample database from 2009-2014. PRA were selected using International Classification of Diseases-Ninth Revision, Clinical Modification diagnosis code (238.77). Multivariate regression analysis was performed to determine mortality and length of stay (LOS) in PRA. Results: The incidence of PRA in transplant-related hospital admissions was 7.19 per thousand admissions (pta) in 2009 and 7.24 pta in 2014 with annual percentage change (APC) of 0.1% (p = 0.9). The median age of patients with PRA was 47 (25-75 percentile: 19-61) years, 38.8% were females, 69.9% were white and 10.7% were African-American. Among patients with PRA, 91.1% had SOT [kidney (31.4%), liver (20.9%), heart (14.6%), lung (7%) and small intestines (1.89%)]; 7.1% had NSOT [bone marrow (3.9%) and peripheral stem cell (2%)] and 1.8% had two or more organ transplants. The most common principal diagnosis in PRA were complications of organ transplant (33.3%), encounter for anti-neoplastic chemotherapy (11.4%), neutropenia (5%), acute kidney injury (3.7%) and hearing loss (1.7%). Among transplant-related hospital admissions, PRA had higher adjusted odds of inpatient mortality [Odds ratio (OR) 2.57 (Confidence Interval (CI) 1.69-2.42), p < 0.001] and longer LOS [4.22 days (CI 3.26-5.17), p < 0.001] than non-PRA. Among PRA, those with NSOT have higher adjusted odds of mortality [OR 2.98 (CI 1.07-8.29), p = 0.036] and longer LOS [16.27 days (CI 3.51-29.03), p < 0.013] compared to those with SOT. Conclusions: PRA have higher odds of mortality and longer LOS compared to other transplant-related hospital admissions. Even though SOT accounts for most of the PRA, the adjusted odds of mortality are significantly higher in PRA with NSOT.

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