Survival Comparison of Three Treatment Regimens of POEMS Syndrome: A Single-Center Retrospective Study

Abstract OBJECTIVE: POEMS syndrome is a rare plasma cell dyscrasia and there is currently no standard treatment. Current treatments include melphalan, autologous stem cell transplantation (ASCT) and novel regimens. However, the efficacy of these treatments has not previously been retrospectively compared in large cohorts. Therefore, this study aims to compare the efficacy and survival of three treatment regimens in patients with POEMS syndrome in our 18-year cohort. METHODS: We retrospectively analyzed the clinical records of 347 patients with newly diagnosed POEMS syndrome who were diagnosed and treated in our hospital from January 2000 to December 2017 with complete treatment and follow-up data. Patients were divided into three groups according to the initial first-line treatment regimen: melphalan + dexamethasone (MDex, N = 79) for 9 months, autologous stem cell transplantation (ASCT, N = 165), or lenalidomide + dexamethasone for 1 year (LDex, N= 103). Hematologic complete remission rates (CRH), vascular endothelial growth factor (VEGF) complete remission rates (CRV), and neurological remission rates (RN) were compared for three regimens, as well as progression-free survival (PFS) and overall survival (OS). Hematologic complete remission was negative IFE and no FLC in serum or urine. The VEGF complete remission was normalized VEGF (<600 pg/ml). The neurological response was defined as the reduction of ONLS by more than 1 point. Remission rates were compared by Pearson ӽ 2 test or Fisher's exact test. Survival curves were plotted by the Kaplan-Meier method and tested using a log-rank test. Subgroup analyses were based on risk stratification and heterogeneous baseline characteristics between treatment groups. RESULTS: Patients in the ASCT group achieved significantly higher rates of CRV (66.2%), which were superior to the MDex group (38.5%, p = 0.001) and the LDex group (47.7%, p = 0.006). There were no significant differences in CRH and RN between the three groups: CRH (MDex 37.7% vs ASCT 49.7% vs LDex 47.5%, p = 0.244) and RN (MDex 100% vs ASCT 91.% vs LDex 93.8%, p = 0.234). However, the proportion of low risk patients in the ASCT group was significantly higher than that in the MDex and LDex groups (44.2% vs 22.8% & 26.2%, p=0.001). Therefore, we performed a subgroup analysis. Subgroup analysis showed that the CRV in the ASCT group was similar to that in MDex and LDex groups in the low-risk group (p = 0.222), but there was a significant advantage in the middle- and high-risk patients (p = 0.001). After a median follow-up of 45 months, a total of 49 deaths occurred and 50 patients developed disease progressions but remained alive. The 3-year PFS was 83.7% for MDex group, 87.9% for ASCT group, and 65.2% for LDex groups. The 3-year OS was as follows: MDex group 90.6%, ASCT group 94.4%, and LDex group 81.6%. The ASCT group achieved a better PFS than the LDex group (p = 0.003), while the three groups had no significant differences in 3-year OS (p = 0.069). CONCLUSION: All three treatment regimens have achieved good efficacy and survival in the treatment of POEMS syndrome. Compared with melphalan and lenalidomide-based regimens, patients at medium to high risk may benefit more from autologous transplantation. Disclosures No relevant conflicts of interest to declare.

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Azacitidine Maintenance after Allogeneic Stem Cell Transplantation Is Feasible in Patients with Acute Myeloid Leukemia and Myelodysplasia

Blood ◽

10.1182/blood.v124.21.5884.5884 ◽

2014 ◽

Vol 124 (21) ◽

pp. 5884-5884 ◽

Cited By ~ 6

Author(s):

Ahmad Antar ◽

Mohamed A Kharfan-Dabaja ◽

Hussein Abou Ghaddara ◽

Rami Mahfouz ◽

Ali Bazarbachi

Keyword(s):

Acute Myeloid Leukemia ◽

Stem Cell ◽

High Risk ◽

Complete Remission ◽

Stem Cell Transplantation ◽

Maintenance Therapy ◽

Myeloid Leukemia ◽

Abnormal Karyotype ◽

Acute Myeloid

Abstract Background: 5-Azacidine (5-AZA) is a DNA hypomethylating agent with proven clinical activity in myelodysplastic syndromes (MDS) and acute myeloid leukemia (AML). A recent non-randomized study reported promising results with the use of lower doses of 5-AZA as maintenance therapy after hematopoietic stem cell transplantation (HSCT). It is important to note that 5-AZA has an immunomodulatory effect and might enhance the graft-versus-leukemia (GVL) effect. Here, we report the successful use of 5-AZA maintenance following allogeneic HSCT in patients with high risk AML and MDS. Patients and methods: Nine patients (M=6, F=3; median age=49 (36-65) years ) with high-risk AML (n=6 including 2 abnormal karyotypes) or MDS (n=3 including 1 abnormal karyotype) received 5-AZA as post-transplant maintenance at a dose of 32mg/m2 daily for 5 days every 4 weeks starting at a median time of 100 (30-210) days post-transplant. All patients were in complete remission at initiation of 5-AZA. A median of 12 cycles (1-18) were delivered. Patients’ characteristics, treatment details, response and side effects are summarized in Table I. Results: After a median follow-up of 19 months post HSCT and 15 months after starting 5-AZA treatment, five patients with normal karyotype are still in CR. Conversely, all three patients with abnormal karyotype rapidly developed disease recurrence while they were receiving 5-AZA after a median of 3 months. Overall, the actuarial 1-year progression free and overall survival rates were 65% and 90%, respectively. 5-AZA was generally well tolerated with only mild thrombocytopenia observed in 2 patients. No clinically evident graft-versus-host disease exacerbation was observed. Conclusion: These results suggest that Low-dose 5-AZA is an effective maintenance therapy post- allogeneic SCT in high-risk AML and MDS particularly when a normal diploid karyotype is present. The relative lack of efficacy in the presence of an abnormal karyotype is intriguing and questions whether these subjects might benefit from higher doses of 5-AZA or other novel therapies within the context of a well-designed clinical trial. Prospective clinical trials and longer follow-up are needed to confirm these observations. Abstract 5884 TABLE I.Patients characteristics and Outcomes After Azacitidine maintenanceSubject #123456789Age at transplant655848433649495851genderMMFMFMFMMDiseaseAMLAMLAMLAMLSecondary AMLSecondary AMLMPD/MDSMDS (RAEB-2)MDS (RAEB-2)cytogeneticnormalnormalT(6,9)normalDel 5normalnormalnormalHypoploidy(43-45)Molecular abnormalityNoneNoneNoneFLT3 ITDNoneNoneNoneNoneNoneDisease status at HSCTCR2CR3CR1CR1RefractoryCR1PRPRCR1Donor typeMRDMRDMRDMRDMUDMRDMRDMRDMRDConditioningFB2+ATGFB3+ATGFB3+ATGFB4+ATGFB3+ATG+ TBI (4Gy)FB4+ATGFB4+ATGFB3+ATGFB2+ATGGVHD prophylaxisCSACSACSACSACSACSACSACSACSA, mycophenolate mofetilTime from HSCT to 5-AZA (days)37701001503021010055104Disease status at 5-AZACRCRCRCRCRCRCRCRCRnb of cycles12131241218129ToxicityNoneNoneNoneNoneGrade II thrombocytopeniaGrade II thrombocytopeniaNoneNoneNoneGVHD after 5-AZANoNoYesYesYesNoYesNoNoDisease recurrencenonoyesnoyesnononoyesSalvage therapy if recurrenceN/AN/AChemotherapy followed by DLIN/ANoneN/AN/AN/AChemotherapy followed by DLIProgression free survival, months13+24+124+319+21+18+10Status at last follow upCRCRCRCRdiedCRCRCRCRSurvival, months13+24+18+24+519+21+18+34+ Stem cell source for all patients: peripheral blood; CR: complete remission; PR: partial remission; CSA: cyclosporine A; MRD: matched related donor; MUD: matched unrelated donor; PBSC: peripheral blood stem cell; CCR: continuous complete remission; FB4: 5 days fludarabine plus 4 days busulfan (130 mg/m2/day); FB3: 5 days fludarabine plus 3 days busulfan (130 mg/m2/day); FB2: 5 days fludarabine plus 2 days busulfan (130 mg/m2/day) ATG: anti-thymoglobuline; DLI: donor lymphocyte infusion. Disclosures Off Label Use: Azacitidine maitenance post HSCT.

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Impact of Deletion 17p On the Outcome of Autologous Hematopoietic Stem Cell Transplantation in Multiple Myeloma.

Blood ◽

10.1182/blood.v120.21.3099.3099 ◽

2012 ◽

Vol 120 (21) ◽

pp. 3099-3099

Author(s):

Caitlin L. Costello ◽

Edward D. Ball ◽

Sue Corringham ◽

Hongying Li ◽

Karen Messer

Keyword(s):

Multiple Myeloma ◽

Stem Cell ◽

High Risk ◽

Complete Remission ◽

Stem Cell Transplantation ◽

Chromosomal Abnormalities ◽

Treatment Plan ◽

Normal Cytogenetics ◽

The Impact

Abstract Abstract 3099 Background: The development of a risk-stratification model that relies on molecular cytogenetic markers to assess disease aggressiveness and provide therapeutic guidance would be beneficial for the management of patients with multiple myeloma (MM). High-risk cytogenetic abnormalities, including deletion 17p (del17p), are known to confer a poor prognosis. Intensified consolidation with high-dose therapy (HDT) and autologous stem cell transplantation (ASCT) following induction therapy has been proposed as the preferred initial treatment for high-risk MM, such as del17p. With this background, we report the impact of del17p on the timing and outcome of transplant in patients with MM. Methods: We performed a retrospective review of 226 patients with MM who underwent HDT/ASCT at the University of California, San Diego Moores Cancer Center between 1/2000 and 7/2011. Conventional cytogenetic analyses were utilized for all patients either at diagnosis or at relapse, but prior to ASCT. Fluorescence in situ hybridization was also assessed when available. The primary objective was to evaluate the impact of del17p, a known high-risk chromosomal abnormality, on the overall survival (OS) and progression-free survival (PFS) after ASCT, compared with patients without chromosomal abnormalities. A secondary objective was to assess the OS and PFS for patients with del17p who received ASCT within a year of diagnosis, compared with those who underwent ASCT more than 12 months from diagnosis. Results: In 226 patients with conventional cytogenetic data prior to ASCT, chromosomal abnormalities were noted in 82 (36%) patients. Of these, 21 (25%) patients harbored a del17p abnormality. Table 1 shows the patient characteristics and ASCT outcomes. Prior to undergoing ASCT, 4 (19%)patients with del17p achieved a complete remission (CR) or stringent complete remission (sCR), and 6 (29%) achieved a CR or sCR after ASCT. In patients without chromosomal abnormalities, 19 (13%) achieved CR or sCR prior to ASCT, and 45 (31%) achieved it after ASCT. Median follow-up of surviving patients was 47 months (range 5–283). Median PFS after ASCT in patients with del17p and normal cytogenetics were 8.3 months (95%CI: 4.6-N/A) and 33 months (95%CI: 21.7–61.8), respectively (HR 2.15, 95%CI: 1.19–3.89; p=0.011) (Figure 1). Median OS after ASCT in patients with del17p and normal cytogenetics were 47.5 months (95%CI: 19.9-N/A) and 68 months (95%CI 51.1-N/A), respectively (HR: 2.27, 95%CI 1.15–4.48; p=0.018) (Figure 2). Median PFS in patients with del17p who received an ASCT after 12 months and within 12 months from diagnosis was 6.13 months (95%CI: 2.7-NA) and 22.6 months (95%CI: 5.4-NA), respectively (HR=1.22, 95%CI 0.40–3.82; p=0.71). Median OS in del17p patients who received an ASCT after 12 months and within 12 months from diagnosis was 65.6 months (95%CI: 19.3-NA) and 47.5 months (95%CI: 19.9-NA), respectively (HR=0.97, 95%CI 0.26–3.62; p=0.96). Conclusions: In this single center study with long follow up, we demonstrate that a del17p abnormality in MM confers a shorter PFS and OS after ASCT. Furthermore, the use of HDT/ASCT as part of the upfront treatment plan within 12 months of diagnosis does not significantly affect the outcome in patients with a del17p abnormality. Further studies are required to better define a risk-stratified treatment plan for this subset of high-risk multiple myeloma. Disclosures: No relevant conflicts of interest to declare.

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Outcome Of Chronic Lymphocytic Leukemia (CLL) Patients That Failed Allogeneic Stem Cell Transplantation

Blood ◽

10.1182/blood.v122.21.2880.2880 ◽

2013 ◽

Vol 122 (21) ◽

pp. 2880-2880

Author(s):

Ohad Benjamini ◽

Uri Rozovski ◽

Preetesh Jain ◽

William G. Wierda ◽

Susan O'Brien ◽

...

Keyword(s):

Stem Cell ◽

High Risk ◽

Stem Cell Transplantation ◽

Treatment Modality ◽

Treatment Options ◽

Salvage Treatment ◽

Treatment Regimens ◽

Immune Manipulation ◽

Btk Inhibitor

Abstract Introduction Allogeneic hematopoietic stem cell transplantation (allo-SCT) has become a therapeutic option for patients (pts) with high risk CLL. The major cause of allo-SCT failure is relapse or disease progression. No standard treatment is available for pts who failed allo-SCT and post-SCT immune manipulation, and the prognosis of these pts is largely unknown. Methods We performed a retrospective intention-to-treat analysis of pts with CLL who failed allo-SCT and post-SCT immune manipulation between 1998 and 2012 and were referred to the Leukemia Department at MD Anderson Cancer Center for further treatment. Results Seventy-three pts with CLL (n=40, 55%) or Richter's transformation (RT, n=33, 45%) who failed or progressed after allo-SCT were referred for further management at a median of 7 months (range 0-85 months) after allo-SCT. Most pts (n=63, 86%) had received non-myeloablative conditioning and 32 (44%) received post allo-SCT donor lymphocyte infusion (DLI). Six patients (8%) had early (4 pts) or late (2 pts) graft failure. Fifty four (74%) pts were male and the median age at time of failure/progression was 59 yrs (range 32–73 yrs). Of the 73 pts, 68 (93%) received salvage therapy, 1 pt died before treatment was initiated, and 4 pts were considering treatment options at time of last follow-up. A median of 2 treatment regimens (range 0 - 8) were administered between time of post-SCT progression and last follow-up. The most common salvage treatment regimens were chemo-immunotherapy with rituximab (R): R-HyperCVAD (n=24, 33%), OFAR (n=13, 18%), FCR, FBR, PCR, BR (n=24, 33%), immune-modulators thalidomide or lenalidomide (n=21, 29%), alemtuzumab with or without chemotherapy (n=12, 16%), and Bruton's Tyrosine Kinase (BTK) inhibitor (n=5, 7%). At time of last follow up, 26 pts (36%) were alive. The median overall survival (OS) from time of progression after allo-SCT was 33 months (95% CI, 27– 39) and 60% of the pts were alive 2 years from time of progression. Median OS after allo-SCT failure/progression was 53 months (95% CI, 9–97) for CLL pts and 28 months (95% CI, 12–44) for pts with RT (Log Rank: P<0.0001) (Figure 1). Only 4 pts achieved CR following first salvage treatment. The OS of these pts was 152, 41, 26+, 38+ months (the latter 2 are still alive). Pts with partial response (PR), no-response (NR) or progression after first salvage treatment had similar OS. To identify the best treatment modality we analyzed the OS from progression and from time of initiation of treatment to last follow-up of all regimens used. We found that patients treated with either FCR, alemtuzumab or combination chemotherapy did not have significant difference in OS. Remarkably, 4 of 5 pts treated with BTK inhibitor were alive at time of last follow-up. Univariable analyses showed shorter OS for pts with a higher ECOG performance status (PS; P=0.036), low hemoglobin (Hb) (P=0.0001), low albumin (P=0.0001), complex cytogenetic abnormalities at last follow up (P=0.026) and RT (P=0.0001). The multivariable Cox model analyses including age, sex, previous DLI, unfavorable cytogenetic abnormalities before or after allo-SCT, albumin, absolute lymphocyte count and platelet count, identified only Hb (P=0.009, 95% CI; 0.58 - 0.93), ECOG 3 (P=0.036, 95% CI; 1.12 - 30.04) and RT (P=0.002, 95% CI: 1.51 - 6.50) as independently associated with shorter OS. Conclusions The median OS of pts with high-risk CLL or RT from time of allo-SCT failure/progression was 33 months. The longest OS was observed in pts who attained CR after first salvage treatment (4/73, 6%). At the time of analysis, the 50% OS of pts treated with BTK inhibitors was not reached, however, no treatment modality appeared to be superior. Future studies of treatment options for pts that progress after allo-SCT are warranted. Disclosures: Off Label Use: Ibrutinib for CLL therapy.

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Experiences with Haploidentical Allogeneic Blood STEM CELL Transplantation for High-Risk Hematologic Disease in a Colombian Reference Center

Blood ◽

10.1182/blood.v128.22.5882.5882 ◽

2016 ◽

Vol 128 (22) ◽

pp. 5882-5882

Author(s):

Claudia Lucia Sossa Melo ◽

Sara Sanguino Jimenez ◽

Angela Peña Castellanos ◽

Luis Antonio Salazar Montaño ◽

Sonia Osma ◽

...

Keyword(s):

Stem Cell ◽

High Risk ◽

Complete Remission ◽

Stem Cell Transplantation ◽

Myelodysplastic Syndrome ◽

Hematologic Disease ◽

Post Transplantation ◽

Conditioning Therapy ◽

Grade Iii

Abstract BACKGROUND: The scarce of unrelated donors and high costs hamper this treatment modality in Colombia. Alternative donors, such as related haploidentical donors, might contribute to a desired increase in transplant activity. OBJECTIVE: Describe sociodemographic and clinical characteristics of patients taken to haploidentical hematopoietic stem cell transplantation (HHSCT) in Fundación Oftalmológica de Santander (FOSCAL), Santander Colombia and report de early outcomes for overall survival (OS) at 100 days and 1 year of follow up. METHODS: We reviewed 11 patients taken to (HHSCT) at our institution between January 2014 and April 2016. Patients were eligible for (HHSCT) if they did not have an HLA matched related or 10/10 matched unrelated donor (MUD). Conditioning therapy included a thiotepa, fludarabine and busulfan, Graft-versus-host disease (GVHD) prophylaxis was with post-transplantation cyclophosphamide, calcineurin inhibitor and mycophenolate. OS was estimated at 100 days and at 1 year of follow up. RESULTS: Since January 2014 we have conducted eleven haploidentical T-cell repleted transplants. The median age was 25 (range 16-57) years with a HCT-CI score of 0 in 9/11 (81%) of patients and score 1 in 2/11 (19%). The ECOG performance status was 0 in 9/11 (81%) and 2/11 (status 1-2). Seven patients (63%) were male and 4 (37%) were female. Conditioning therapy with thiotepa, fludarabine, busulfan was utilized in 10/11 (90%) of patients and fludarabine, busulfan without thiotepa was utilized in 1/11 (10%) patient. The majority of patients had acute lymphoblastic leukemia 7 (63%), followed by acute myeloid leukemia 2 (18%), myelodysplastic syndrome 1 (9%) and 1 patient (9%) had acute leukemia mixed phenotype and the other one Hodgkin disease. At the time of transplant 10 patients (90%) were in complete remission, whereas 1 patient (9%) with myelodysplastic syndrome was treated with intent to achive remission, but no complete remission was achived. The majority of patients (90%) achieved 100% donor chimerism at day +28. The median time to neutrophil ≥ 0,5 x 109/L was 18 days (range 13-29) and platelets ≥ 20 x 109/L was 22 (range 10-110). Acute GVHD was seen in seven patients. Five were classified as grade II, one patient as grade I and other one as grade III. Chronic GVHD of mild severity was observed in five patients. The major post transplant complication causing significant morbidity and prolonged hospitalization was hemorrhagic cystitis (HC). It appeared as complicated grade III disease in two patients and both had evidence of co-infection with polyomavirus, adenovirus and CMV. Evidence of CMV reactivation was detected in 7 patients successfully eradicated. Evidence of EBV viremia/reactivation was found in 6 patients of whom three patients were treated with rituximab (Table 1). The OS within a median follow up of 12 months was 100%. Two patients with B-ALL and Hodgkin disease relapsed, 13 and 10,7 months post-transplantation respectively. CONCLUSION Although few patients, this type of transplant is an alternative for our patients without HLA-matched donor available, with low mortality and similar complications and outcomes to those using other donor types in high-risk hematologic disease. Disclosures No relevant conflicts of interest to declare.

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Prolonged Remissions with Autologous and Allogeneic Stem Cell Transplantation for Burkitt’s Lymphoma: Long Term Follow-Up at a Single Institution.

Blood ◽

10.1182/blood.v106.11.1133.1133 ◽

2005 ◽

Vol 106 (11) ◽

pp. 1133-1133

Author(s):

Purvi Gada ◽

Todd Defor ◽

Daniel J. Weisdorf ◽

Jeffrey S. Miller ◽

Paul J. Orchard ◽

...

Keyword(s):

Risk Factors ◽

Stem Cell ◽

High Risk ◽

Complete Remission ◽

Stem Cell Transplantation ◽

Cell Transplantation ◽

Advanced Stage ◽

Hematopoietic Stem ◽

High Risk Factors

Abstract Burkitts Lymphoma (BL) is a highly aggressive form of non-Hodgkins lymphoma (NHL) that accounts for 50% of childhood cases of NHL, yet is rare in adults. B symptoms, advanced stage and extranodal disease are risk factors previously associated with poor survival. Hematopoietic stem cell transplantation (HCT) is often used because of either incomplete or short duration of remission with standard therapy yet little published data for HCT and BL exists. We evaluated the comparative safety and efficacy of a cyclophosphamide/total body irradiation-containing myeloablative conditioning regimen followed by either an autologous HCT (autoHCT) or allogeneic related donor HCT (alloHCT) in 38 patients who received transplants between October 1975 and June 2004. Twenty-five patients (median age 16 years [range, 4–65]) underwent an autoHCT; 13 patients (median age 13 [range, 4–62]) received an alloHCT. The median number of conventional chemotherapy regimens prior to transplant was 2 (range 1–4); the median duration of first complete remission (CR) was 0.4 years (range, 0–8.8). The majority of patients were in a complete remission (CR) at transplant (auto HCT - 16 [64%] [40% CR1]), alloHCT - 9 [69%] [23% CR1]). Patient demographics, disease characteristics at diagnosis, at relapse and at transplant were comparable between the two groups except for a greater incidence of high risk factors, including B symptoms, advanced stage at diagnosis, and extranodal (bone marrow and central nervous system) disease in the alloHCT group. The median follow up is 7 years (range 1–12) and 24 years (range 2–27) for the autoHCT and alloHCT groups, respectively. Post-transplant, 71% of auto-HCT and 75% of the alloHCT recipients obtained a CR. The 1-year treatment related mortality (TRM) was comparable in the two groups: 8% and 15% for the autoHCT and alloHCT groups, respectively (p=NS). Ten-year progression free survival (PFS) was 21% (95% CI, 4–38%) and overall survival (OS) 23% (95% CI, 5–41%) after autoHCT compared to 31% (95% CI, 6–66%) and 31% (95% CI, 6–66%) for alloHCT (p=NS). Six patients in autoHCT group and 3 in alloHCT survive disease free between 1 and 27 years; 5 survive beyond 10 years and 3 beyond 15 years from HCT. Donor choice did not significantly alter PFS. Two factors were predictive of superior PFS: fewer chemotherapy regimens prior to transplantation (1 vs ≥ 2) and CR (vs relapsed/persistent disease) at time of transplant. Patients with high risk factors more commonly underwent alloHCT, yet outcomes were comparable to autoHCT, suggesting that a powerful and durable graft versus lymphoma effect exists. These results demonstrate that prolonged remissions can be obtained with either auto or alloHCT, especially for high risk patients in CR. New approaches for patients in relapse are needed to improve these outcomes.

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A Phase II Study of Decitabine Followed By Allogeneic Hematopoietic Stem Cell Transplantation in High-Risk Patients with Myeloid Malignancies

Blood ◽

10.1182/blood-2018-99-112670 ◽

2018 ◽

Vol 132 (Supplement 1) ◽

pp. 2107-2107

Author(s):

Christopher R. D'Angelo ◽

Aric C. Hall ◽

Kyungmann Kim ◽

Ryan J. Mattison ◽

Walter L. Longo ◽

...

Keyword(s):

Stem Cell ◽

High Risk ◽

Hematopoietic Stem Cell Transplantation ◽

Stem Cell Transplantation ◽

Chronic Gvhd ◽

Infectious Complications ◽

Myeloablative Conditioning ◽

Hematopoietic Stem ◽

Post Transplant ◽

Risk Patients

Abstract Introduction: Allogeneic hematopoietic stem cell transplantation (allo-HSCT) is the only curative therapy for myelodysplastic syndrome (MDS) and high-risk acute myeloid leukemia (AML). Patients with high-risk disease have a markedly increased risk of relapse and death following transplant (Armand et al, Blood, 2014). Those who remain disease-free are at risk of severe morbidity from graft-versus- host-disease (GvHD). These issues highlight the importance of improved allo-HSCT platforms designed to reduce relapse rate without increasing risk of GvHD. Decitabine has minimal non-hematologic toxicity and proven efficacy in myeloid diseases (Blum et al, PNAS, 2010). Use of post-transplant cyclophosphamide has demonstrated improved rates of GvHD following allo-HSCT using haplo-identical donors (Bashey et al, JCO, 2013). No studies have reported on outcomes in patients undergoing decitabine immediately prior to transplantation followed by post-transplant cyclophosphamide (PTCy). We hypothesized that the combination of decitabine induction prior to transplant and PTCy would be safe and result in improved disease control with low rates of GVHD, translating into improved survival in a high-risk transplant cohort. Methods In this single-arm, single institution trial, eligible patients received 10 days of IV decitabine at 20mg/m2 no sooner than 24 days and no later than 17 days prior to conditioning. Myeloablative conditioning included fludarabine (50mg/m2 day-5-2), busulfan (IV 3.2mg/kg/day -5-2), and 4 Gy total body irradiation on day -1. Patients above age 65 received a 25% busulfan dose reduction. Patients received a fully or partially matched related bone marrow graft on day 0. GvHD prophylaxis included 50mg/kg of IV cyclophosphamide on day +3-4. Patients with fully matched donors received only PTCy while those with partially matched donors also received mycophenolate mofetil through day +35 and tacrolimus through day +180. Results We enrolled 20 patients, fifteen patients with AML and 5 with MDS. The cohort had a median age of 64 (29-73) and was predominantly male (14/20, 70%). Eight (40%) patients scored as high risk by the HSCT comorbidity index. Eighteen patients (90%) had a high or very high-risk score by the refined disease risk index. All patients received decitabine and 18/20 (90%) underwent transplantation; 2 patients did not receive a transplant due to infectious complications. The majority of patients received a haplo-identical graft (13/18, 72%), and the remaining 5 received a matched related graft. Outcomes are reported in table 2 and figure 1. There were no engraftment failures. Five patients, 3 MDS and 2 AML, are long-term survivors with median follow-up over 3 years. One patient developed donor derived MDS and required a second transplant. Most transplanted patients (13/18, 72%) survived to day 100 with a median post-transplant survival of 138 days. There were 15 deaths on study with the majority due to underlying disease. Six patients (6/20, 30%) died of infectious complications or did not receive a transplant due to infection. Incidence of grade 3-4 acute GvHD was low among those surviving at least 40 days from transplant (3/17, 17%). There were also low rates of chronic GvHD among the 12 patients alive without ongoing GvHD at day 100 (2/12, 17%). Conclusions Decitabine induction followed by myeloablative conditioning in this high-risk population resulted in a high treatment related mortality of 40%. Still, outcomes fell into an expected range for high-risk myeloid disease in an elderly and comorbid population. Based on expected outcomes for high-risk patients from the literature (Armand et al, Blood, 2014), decitabine did not markedly improve overall survival outcomes, recognizing that no direct comparisons are available in our limited study population. Decitabine may increase the risk of peri-transplant infections by contributing to a cumulative immunologic insult combined with disease-related immunosuppression and transplant-related toxicity, highlighting the importance of strict vigilance for infections within this setting. Diligent monitoring may improve infectious outcomes as shown in the second half of the cohort; only two out of the latter 10 patients on protocol died of treatment related complications. There were no cases of engraftment failure. Rates of acute and chronic GvHD using a PTCy platform were low and support other studies reporting this benefit. Disclosures No relevant conflicts of interest to declare.

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