Autologous and Allogeneic Hematopoietic Cell Transplantation

Selected Abstracts From the 2016 ASH Annual Meeting


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Syed Abutalib, MD, Assistant Director in the Stem Cell Transplant & Cell Therapy
Program at Cancer Treatment Centers of America in Chicago

Syed Abutalib, MD, Assistant Director in the Stem Cell Transplant & Cell Therapy Program at Cancer Treatment Centers of America in Chicago

HERE ARE SEVERAL ABSTRACTS selected from the proceedings of the 2016 American Society of Hematology (ASH) Annual Meeting & Exposition, highlighting clinical trials on autologous and allogeneic hematopoietic cell transplantation for various hematologic malignancies. Additional selected abstracts on both autologous and allogeneic hematopoietic cell transplantation from the 2016 ASH Annual Meeting can be found online at http://www.ascopost.com. 

Autologous Transplant 

ABSTRACT LBA1: Primary results of three-arm randomized phase III trial of the Blood and Marrow Transplant Clinical Trials Network (BMT CTN 0702 – StaMINA Trial). Comparison of (1) autologous hematopoietic cell transplant, lenalidomide (Revlimid), bortezomib (Velcade), and dexamethasone (RVD) consolidation (× 4 cycles) with lenalidomide maintenance (n = 254); (2) tandem autologous hematopoietic cell transplant with lenalidomide maintenance (n = 247); and (3) autologous hematopoietic cell transplant with lenalidomide maintenance (n = 257) for upfront treatment of patients with multiple myeloma1 

Study Endpoint: Progression-free survival, with a median available follow-up from randomization of 38 months 

Study Conclusion: The 38-month estimated probabilities for progression-free survival were 57% (95% confidence interval [CI] = 50-63%), 56% (95% CI = 49%–63%), and 52% (95% CI = 45%–59%) for autologous transplant/consolidation/lenalidomide maintenance, tandem autologous transplant/lenalidomide maintenance, and autologous transplant/lenalidomide maintenance, respectively (autologous transplant/consolidation/lenalidomide maintenance vs tandem autologous transplant/lenalidomide maintenance, P = .75; autologous transplant/consolidation/lenalidomide maintenance vs autologous transplant/lenalidomide maintenance, P = .21; tandem autologous transplant/lenalidomide maintenance vs autologous transplant/lenalidomide maintenance, P = .37). Corresponding probabilities of overall survival were 86% (95% CI = 80%–90%), 82% (95% CI = 76%–87%), and 83% (95% CI = 78%–88%), respectively. Median overall survival has not been reached. 

Cumulative incidences of disease progression at 38 months were 42% (95% CI = 36%–48%), 42% (95% CI = 35%–48%), and 47% (95% CI = 40%–54%) for the autologous transplant/consolidation/ lenalidomide maintenance, tandem autologous transplant/lenalidomide maintenance, and autologous transplant/lenalidomide maintenance arms, respectively. There were 39 cases of second primary malignancy reported in 36 participants, and the cumulative incidences for first second primary malignancy were 6.0% (95% CI = 3.4%–9.6%), 5.9% (95% CI = 3.3%–9.6%), and 4.0% (95% CI = 1.9%–7.2%) for autologous transplant/consolidation/lenalidomide maintenance, tandem autologous transplant/lenalidomide maintenance, and autologous transplant/lenalidomide maintenance, respectively. Noncompliance rates following the first autologous hematopoietic cell transplant were 12%, 32%, and 5% for autologous transplant/consolidation/lenalidomide maintenance, tandem autologous transplant/lenalidomide maintenance, and autologous transplant/lenalidomide maintenance, respectively. 

Clinical Implications: The addition of RVD consolidation or a second autologous hematopoietic cell transplant was not superior to a single autologous hematopoietic cell transplant followed by lenalidomide maintenance in the upfront treatment of multiple myeloma. A long-term follow-up trial to track outcomes in these patients is ongoing. 

ABSTRACT 986: Clonal hematopoiesis of indeterminate potential is associated with adverse outcomes following autologous hematopoietic cell transplant in patients with non-Hodgkin lymphomas (NHLs).

Study Endpoints: How clonal hematopoiesis of indeterminate potential behaves and influences outcomes in the context of autologous hematopoietic cell transplant 

Study Conclusion: In 7 of 10 patients with treatment-related neoplasms, aberrant mutations were also detectable in the sample prior to autologous hematopoietic cell transplant. PPM1D, a key mediator of the DNA damage pathway, was mutated in two patients, with TP53 mutated in two patients, TET2 mutated in two patients, and PRPF8 mutated in one patient). In our larger cohort of 401 unselected autologous hematopoietic cell transplant patients, clonal hematopoiesis of indeterminate potential was common (121 patients, 30.2%) and associated with older age but not with other demographic or treatment-related factors; and 18 patients developed myeloid neoplasm. PPM1D was the most commonly mutated gene (54 mutations in 48 patients). 

The presence of clonal hematopoiesis of indeterminate potential at the time of autologous hematopoietic cell transplant significantly increased this risk of treatment-related myeloid neoplasm. The 10-year cumulative incidence of treatment-related myeloid neoplasm, with death and allogeneic transplant as competing risks, was 12.4% for patients with clonal hematopoiesis of indeterminate potential, compared with 3.5% for patients without (P = .002). Moreover, the presence of clonal hematopoiesis of indeterminate potential at the time of autologous hematopoietic cell transplant conferred significant risks beyond treatment-related myeloid neoplasm alone, as patients with clonal hematopoiesis of indeterminate potential had significantly inferior overall survival compared with patients without (10-year overall survival 30.6% vs 60.9%, P = .0003). This difference was driven primarily by late mortality and not by an increased risk of relapse or by the difference in the rate of treatment-related myeloid neoplasm. 

Clinical Implications: These data suggest the need to specifically study the connection between clonal hematopoiesis of indeterminate potential and lymphoma more deeply, which could be accomplished by assessing clonal hematopoiesis of indeterminate potential in patients with newly diagnosed lymphoma prior to the administration of any chemotherapy or mobilizing agents. These data also suggest the need to consider alternative therapeutic approaches for patients with lymphoma and a high risk of treatment-related myeloid neoplasms who are being considered for autologous hematopoietic cell transplant.

ABSTRACT 515: Adaptive natural killer (NK)-cell expansion is associated with reduced relapse of lymphoid malignancies after autologous hematopoietic cell transplant.3

Study Endpoint: Do high absolute numbers of CD56dimCD57+NKG2C+ “adaptive” NK cells—ie, natural killer cells that exhibit properties characteristic of adaptive (as opposed to innate) immunity—assessed at day +28 after autologous hematopoietic cell transplant influence outcomes?

“Interventions to increase the numbers of CD56dimCD57+NKG2C+ adaptive NK-cell counts might provide a novel means of preventing relapse following transplant.”
— Syed Abutalib, MD

Study Conclusion: The investigators showed that patients with lymphoid malignancies with high absolute counts of “adaptive” CD56dimCD57+NKG2C+ NK-cell counts (≥ 1.529/μL, n = 88) at day +28 after autologous hematopoietic cell transplant had significantly superior disease-free survival and a lower risk of relapse than did patients with low absolute “adaptive” NK-cell counts (n = 25). There was no difference in the risk of bacterial, fungal, or viral infections or in overall survival between the groups. The cumulative incidence of relapse at 2 years was 34% (95% CI = 23%–44%) in the high-count group compared with 70% (95% CI = 49%–91%) in the low-count group (P = .0012). The 2-year disease-free survival rates were 63% (95% CI = 51%–72%) and 30% (95% CI = 12%–50%), respectively (P = .0032).

Clinical Implications: The protective effect of CD56dimCD57+NKG2C+NK cells on relapse (hazard ratio [HR] = 0.12; 95% CI = 0.05–0.30; P < .0001) and disease-free survival (HR = 0.14; 95% CI = 0.06–0.33; P < .0001) was noted only in cytomegalovirus-seropositive patients, but not in cytomegalovirus-seronegative individuals. In aggregate, these data suggest that interventions to increase the numbers of CD56dimCD57+NKG2C+ adaptive NK-cell counts might provide a novel means of preventing relapse following autologous hematopoietic cell transplant in patients with Hodgkin lymphoma, NHL, and multiple myeloma.

Allogeneic Transplant

ABSTRACT LBA3: Multicenter open-label phase II study of ibrutinib (Imbruvica; 420 mg daily) in chronic graft-vs-host disease after failure of corticosteroids4

Study Endpoint: Response rate with ibrutinib in steroid-failure chronic graft-vs-host disease

Study Conclusion: At a median follow-up of 13.9 months, the overall response rate was 67% (28 of 42 patients; 9 [21%] complete responses, 19 [45%] partial responses), with 20 of 28 (71%) and 12 of 25 (48%) responders showing a sustained response of ≥ 20 and ≥ 32 weeks, respectively. Most responders were able to reduce the steroid dose to an acceptable minimal level. The most common adverse events were fatigue (57%), diarrhea (36%), muscle spasms (29%), nausea (26%), and bruising (24%).

Clinical Implications: Ibrutinib has recently been granted Breakthrough Therapy designation for chronic graft-vs-host disease after failure of one or more lines of systemic therapy.

ABSTRACT 507: Final results of a randomized phase II trial evaluating lower-dose vs higher-dose pomalidomide as therapy for steroid-refractory chronic graft-vs-host disease5 

Study Endpoint: Optimal dose and efficacy of pomalidomide (Pomalyst) in steroid-refractory chronic graft-vs-host disease were study objectives. The primary endpoint was overall response rate at 6 months. 

“Low-dose pomalidomide is a promising new therapy for corticosteroid-refractory chronic graft-vs-host disease.”
— Syed Abutalib, MD

Study Conclusion: Response rates were similar with 0.5 and 2 mg/d, but there were more early treatment discontinuations with 2 mg/d. The overall response rate at 6 months in an intent-to-treat analysis was 47% (n = 15, partial responses). The overall response rate increased to 71% in 21 evaluable subjects. Organs with the most improvement were the skin and joints, suggesting an antifibrotic effect. Median decreases in the prednisone dose compared with baseline were 13% (0%–67%) at 6 months and 63% (17%–81%) at 12 months of pomalidomide treatment. 

Clinical Implications: Low-dose pomalidomide is a promising new therapy for corticosteroid-refractory chronic graft-vs-host disease. Aspirin (325 mg/d) was used as venous thromboembolism prophylaxis. 

ABSTRACT 990: Selection of unrelated allogeneic hematopoietic cell donors based on KIR3DL1 allotypes is feasible and results in improved disease-free survival in transplant recipients with myelodysplastic syndrome and acute myeloid leukemia6 

Study Endpoints: The feasibility to prospectively type and utilize KIR3DL1 allotypes in human leukocyte antigen (HLA)-matched unrelated donor selection algorithm, and the impact of intervention results on outcomes in patients with myelodysplastic syndrome and acute myeloid leukemia. KIR3DL1 is a polymorphic receptor that binds to HLA-A and HLA-B allotypes expressing the Bw4 epitope, which leads to a variety of effects and may have a role in immune responses. 

Study Conclusion: On univariate analysis, the 2-year disease-free survival was 64% (95% CI = 54%–76%) with KIR3DL1- LOW/NO donors vs 39% (22%–68%) in patients with KIR3DL1- HIGH donors (P = .05). The incidence of relapse was similar but favored patients with KIR3DL1-LOW/NO donors (26% [15%–37%] vs 35% [13%–57%], P = .5). The 2-year overall survival was similar between those with KIR3DL1-LOW/NO vs KIR3DL1-HIGH donors (75% [65%–86%] vs 69% [52%–91%], P = .43). Donors were HLA-matched in 105 transplants and were single loci–mismatched in 10 transplants. The time from the initiation of a formalized donor search to transplant did not differ between recipients with KIR3DL1-LOW/NO vs KIR3DL1-HIGH donors (median 81 vs 83 days, respectively, P = .97). 

Clinical Implications: These prospective data on 115 patients from a single center support improved outcomes in patients with myelodysplastic syndrome and acute myeloid leukemia undergoing unrelated donor allogeneic hematopoietic cell transplant using a donor with low or absent KIR3DL1 inhibition. A multicenter, prospective study to evaluate the prospective use of HLA and KIR genotype–based selection of unrelated donors for patients undergoing allogeneic hematopoietic cell transplant for acute myeloid leukemia is underway (ClinicalTrials. gov identifier NCT02450708). 

ABSTRACT 506: Results from a phase III randomized multicenter trial: Sirolimus combined with mycophenolate mofetil and cyclosporine significantly improves prevention of acute graft-vs-host disease after unrelated allogeneic hematopoietic cell transplant in patients conditioned with fludarabine at 90mg/m2 and 2–3 Gy total-body irradiation7 

Study Endpoint: Impact of the addition of sirolimus to mycophenolate mofetil and cyclosporine backbone on the rates of grades 2–4 acute graft-vs-host disease in the unrelated and nonmyeloablative transplant setting 

Study Conclusion: At the time of the interim analysis, 158 patients had been enrolled in total (arm 1 [mycophenolate mofetil and cyclosporine] n = 74; arm 2 [mycophenolate mofetil and cyclosporine plus sirolimus] n = 84). The median age of patients was 62 years (range, 18–79). The median hematopoietic cell transplant– comorbidity index was 3 (range, 0–10). The median follow-up of surviving patients was 24 months (range, 1–65). 

The day-100 cumulative incidences of grades 2–4 acute graft-vs-host disease follow: Arm 1: 53%, and arm 2: 25% (P = .0001); and the grades 3–4 acute graft-vs-host disease were 8% in arm and 2% in arm 2 (P = .04). The 1-year cumulative incidence of chronic extensive graft-vs-host disease was similar between the two arms. The 1-year cumulative incidence of nonrelapse mortality was lower in arm 2 (arm 1: 15%; arm 2: 5%, P = .007), whereas relapse/disease progression was similar at 1 year in the two arms. The 1-year overall and progression-free survival rates for arm 1 vs arm 2 were 72% vs 85% (P = .03), and 65% vs 77% (P = .08), respectively. 

Clinical Implications: According to the investigators, this triple immunosuppressive regimen should be considered as the standard of care in patients given unrelated donor grafts after minimal intensity conditioning. 

DISCLOSURE: Dr. Abutalib reported no conflicts of interest. 

REFERENCES 

1. Stadtmauer EA, Pasquini MC, Blackwell B, et al: Comparison of autologous hematopoietic cell transplant (autoHCT), bortezomib, lenalidomide (Len) and dexamethasone consolidation with Len maintenance, tandem autoHCT with Len maintenance and autoHCT with Len maintenance for up-front treatment of patients with multiple myeloma: Primary results from the randomized phase III trial of the Blood and Marrow Transplant Clinical Trials Network (BMT CTN 0702 – StaMINA Trial). 2016 ASH Annual Meeting. Abstract LBA-1. Presented December 6, 2016. 

2. Gibson CJ, Lindsley RC, Tchekmedyian V, et al: Clonal hematopoiesis associated with adverse outcomes following autologous stem cell transplantation for non-Hodgkin lymphoma. 2016 ASH Annual Meeting. Abstract 986. Presented December 5, 2016. 

3. Mehta RS, Wangen R, Cichocki F, et al: Adaptive NK cell expansion is associated with reduced relapse of lymphoid malignancies after autologous hematopoietic cell transplant. 2016 ASH Annual Meeting. Abstract 515. Presented December 4, 2016. 

4. Miklos D, Cutler CS, Arora M, et al: Multicenter open-label phase 2 study of ibrutinib in chronic graft versus host disease after failure of corticosteroids. 2016 ASH Annual Meeting. Abstract LBA-3. Presented December 6, 2016. 

5. Curtis LM, Venzon D, Hakim FT, et al: Final results of a randomized phase 2 trial evaluating lower-dose versus higher-dose pomalidomide as therapy for corticosteroid-refractory chronic Gvhd. 2016 ASH Annual Meeting. Abstract 507. Presented December 4, 2016. 

6. Shaffer BC, Heller G, Le Luduec JB, et al: Selection of unrelated allogeneic hematopoietic cell donors based on KIR3DL1 allotypes is feasible and results in improved disease-free survival in transplant recipients with MDS and AML. 2016 ASH Annual Meeting. Abstract 990. Presented December 5, 2016. 

7. Sandmaier BM, Maloney DG, Storer BE, et al: Sirolimus combined with mycophenolate mofetil and cyclosporine significantly improves prevention of acute graft-versus-host-disease after unrelated hematopoietic cell transplantation: Results from a phase III randomized multi-center trial. 2016 ASH Annual Meeting. Abstract 506. Presented December 4, 2016.

EXCLUSIVE ONLINE CONTENT

Online-only expanded version of Hematology Expert Review by Dr. Syed Abutalib

More on Autologous Transplant

ABSTRACT 514: Retrospective analysis on behalf of the European Society for Blood and Marrow Transplantation: Relapsed nodular lymphocyte-predominant Hodgkin lymphoma: High efficacy of autologous hematopoietic cell transplant 8

Study Endpoint: The primary objective was 5-year progression-free survival.

Study Conclusion: The 5-year incidence of relapse was 32% (95% CI = 20%–46%). There were no transplant-related deaths. The disease status prior to autologous hematopoietic cell transplant was complete remission in 54% and partial remission in 43%.

Clinical Implications: This study demonstrates that patients with chemosensitive disease may benefit from autologous hematopoietic cell transplant.

ABSTRACT 994: Retrospective analysis on behalf of the Center for International Blood & Marrow Transplant Research (CIBMTR): Similar outcomes after autologous hematopoietic cell transplant in multiple myeloma patients with and without renal insufficiency9

Study Endpoint: Comparison of outcomes with various degrees of renal insufficiency in patients who received autologous hematopoietic cell transplant

Study Conclusion: Of the total cohort, 1,240 patients had normal/mild (glomerular filtration rate [GFR] > 60 mL/min), 185 patients had moderate (GFR of 31–59 mL/min), and 67 patients had severe (GFR < 30 mL/min) renal insufficiency. Thirty-five patients were on dialysis prior to autologous hematopoietic cell transplant. Melphalan at the standard dose of 200 mg/m2 was administered in 92% of patients with normal/mild, 75%of patients with moderate, and 33% patients with severe renal insufficiency. Of 35 patients with severe renal insufficiency, 30 achieved dialysis independence.

For patients with moderate renal insufficiency, the probability of progression-free survival at 5 years for patients receiving melphalan at 140 mg/m2 was 18% [95% CI = 6%–35%] and for patients receiving melphalan at 200 mg/m2 was 46% [95% CI = 36%–57%; P = .009). For patients with severe renal insufficiency, the probability of progression-free survival at 5 years for patients receiving melphalan at 140 mg/m2 was 25% [95% CI =11%–41%] and for patients receiving melphalan at 200 mg/m2 was 32% [95% CI = 11%–58%; I = .37).

Clinical Implications: Autologous hematopoietic cell transplant using the standard dose of melphalan appears to be safe and effective in patients with moderate renal insufficiency.

More on Allogeneic Transplant

ABSTRACT 823: Long-term morbidity and mortality experienced by chronic myeloid leukemia (CML) patients (n = 637) after allogeneic hematopoietic cell transplant 10

Study Endpoint: Long-term (median follow-up of 16.7 years from allogeneic hematopoietic cell transplant) health of CML survivors after allogeneic hematopoietic cell transplant

Study Conclusion: Conditional on surviving the first 2 years after allogeneic hematopoietic cell transplant, the overall survival exceeds 70% at 20 years and remains stable at 70% at 30 years after hematopoietic cell transplant. The 20-year cumulative incidence of relapse-related mortality was 3.9% (95% CI = 2.6%–5.8%), and nonrelapse mortality was 18.2% (95% CI = 19.8%–28.1%). Allogeneic hematopoietic cell transplant survivors are at a 2.7-fold higher risk of severe/life-threatening morbidity when compared with siblings. The more common morbidities included secondary myeloid neoplasms, diabetes, and coronary artery disease. However, CML patients receiving hematopoietic cell transplant at < 45 years of age with busulfan and cyclophosphamide conditioning have survival rates exceeding 81% at 20 years from hematopoietic cell transplant, and their burden of long-term morbidity is comparable to that experienced by siblings. The 20-year cumulative incidence of a severe/life-threatening chronic health condition among hematopoietic cell transplant survivors was 47.2% (95% CI = 39.0%–54.9%); the incidence was higher (P = .0006) for matched unrelated donor vs matched related donor recipients.

Clinical Implications: Nonrelapse-related mortality (infections, chronic graft-vs-host disease, and secondary myeloid neoplasms) is by far the major contributor to late mortality. Conditional on surviving the first 15 years, these mortality rates are similar to those observed in the general population. These data could help inform decisions regarding therapeutic options for the management of patients with CML.

ABSTRACT 679: Retrospective, CIBMTR analysis comparing total-body irradiation–based (n = 819) with intravenous busulfan-based chemotherapy only (n = 299) conditioning regimens for myeloablative allogeneic hematopoietic cell transplant in adults with acute lymphoblastic leukemia (ALL)11

Study Endpoint: Equivalency of the two myeloablative conditioning approaches in the setting of HLA-matched sibling donor and HLA-matched unrelated donor transplants for patients with ALL

Abstract Conclusion: With a median follow-up of 3.6 years for the busulfan-based group and 5.3 years for the total-body irradiation–based group, adjusted 3-year outcomes showed transplant-related mortality with busulfan of 19% vs total-body irradiation of 25% (P = .04); relapse rate with busulfan of 37% vs total-body irradiation of 28% (P =.007); disease-free survival with busulfan of 45% vs total-body irradiation of 48% (P =.35); and overall survival with busulfan of 57% vs total-body irradiation of 53% (P =.35).

In multivariate analysis, the busulfan group had a significantly higher rate of acute graft-vs-host disease after day 50 (relative risk [RR] = 1.75; 95% CI = 1.19–2.58; P = .004) but marginally less acute graft-vs-host disease (RR = 0.83; 95% CI = 0.68–1.01; P = .059) and a higher risk of relapse (RR = 1.46; 95% CI = 1.15–1.85; P = .002) compared with total-body irradiation–based regimens.

Clinical Implications: Busulfan-based conditioning resulted in higher rates of acute graft-vs-host disease and relapse but with similar transplant-related mortality, overall survival, and disease-free survival compared with total-body irradiation–based regimens.

ABSTRACT 682: Long-term outcome of allogeneic hematopoietic cell transplant for chronic lymphocytic leukemia (CLL): 10-year follow-up of the GCLLSG CLL3X trial12

Study Endpoints: Long-term outcomes with reduced intensity conditioning allogeneic hematopoietic cell transplant in patients (n = 90) with poor-risk CLL and influence of minimal residual disease on posttransplant outcomes

Study Conclusion: With a median follow-up of survivors of 9.3 years (range, 0.6–15.5 years), 10-year nonrelapse mortality, relapse incidence, event-free survival, and overall survival of all 90 patients were 26%, 57%, 32%, and 51%, respectively. The absence of minimal residual disease at the 12-month landmark posttransplant was highly predictive of an increased risk for relapse (10-year relapse incidence of 25% vs 80% if minimal residual disease was present at the 12-month landmark, P < .0001), in particular if minimal residual disease eradication occurred only after immunosuppression withdrawal, suggesting effective graft-vs-leukemia activity (10-year relapse incidence of 12%). Notably, no relapse event occurred beyond 10 years posttransplant.

Clinical Implications: Reduced intensity conditioning allogeneic hematopoietic cell transplant may provide graft-vs-leukemia–mediated sustained disease control in a sizable proportion of patients with poor-risk CLL independent of TP53 status. Patients who are in minimal residual disease–negative remission 1 year after allogeneic hematopoietic cell transplant have a 75% probability of remaining disease-free at least for 10 years. It is important to note that the indication for allogeneic hematopoietic cell transplant has been further pushed back from success of pathway inhibitors in patients with poor-risk CLL.

ABSTRACT 830: Double-hit and double-expressor relapsed and refractory diffuse large B-cell lymphoma (DLBCL) are not associated with an adverse outcome after allogeneic hematopoietic cell transplant in a retrospective analysis.13

Study Endpoint: Can allogeneic hematopoietic cell transplant abrogate the negative prognostic impact of double-hit and double-expressor relapsed and refractory DLBCL?

Study Conclusion: The 4-year progression-free survival in double-expressor lymphoma vs non–double-expressor lymphoma patients was 29% vs 39% (P = .2); 4-year overall survival was 30% vs 49% (P = .11); 4-year cumulative incidence of relapse was 50% vs 40% (P = .3); and 4-year nonrelapse mortality was 21% vs 22% (P = 1.0). The 4-year progression-free survival in double-hit lymphoma vs non–double-hit lymphoma patients was 40% vs 33% (P = .6); overall survival was 50% vs 37% (P = .4); cumulative incidence of relapse was 40% vs 45% (P = .9); and nonrelapse mortality was 20% vs 22% (P = .8).

Clinical Implications: These retrospective data suggest that allogeneic hematopoietic cell transplant may overcome the chemoresistance of double-hit and double-expressor lymphomas in patients with relapsed and refractory disease.

Miscellaneous

ABSTRACT 70: Retrospective, CIBMTR analysis on unrelated male donors vs sibling parous female donors: Impact on transplant-related outcomes with T-cell–replete grafts14

Study Endpoints: Comparison of grade 2 to 4 acute graft-vs-host disease, chronic graft-vs-host disease, and overall survival between the two groups

Study Conclusion: The cumulative incidence of acute graft-vs-host disease was higher in male unrelated than parous sibling donors at 100 days (46% vs 35%, P < .001. The incidence of chronic graft-vs-host disease at 100 days was also higher in male unrelated donors (9% vs 4%, P < .001) but was not different at 1 and 2 years posttransplant. The donor type did not significantly affect overall survival, leukemia-free survival, transplant-related mortality, or disease relapse.

Clinical Implications: When available, female parous siblings should be utilized rather than male unrelated donors to minimize graft-vs-host disease.

ABSTRACT 683: Comparison of peripheral blood to bone marrow graft for T-cell–replete HLA-haploidentical donor transplantation using posttransplant cyclophosphamide15

Study Endpoint: Influence of graft source on outcomes in this setting

Study Conclusion: The relapse risks were higher after transplantation with bone marrow compared with peripheral blood grafts (HR = 1.49; P = .009; 2-year relapse: 45% and 28%). The median follow-up was 35 and 20 months for recipients of bone marrow and peripheral blood grafts, respectively.

Clinical Implications: In this retrospective analysis, peripheral blood grafts were associated with similar overall survival and nonrelapse mortality but had lower relapse rates with myeloablative conditioning regimens compared with bone marrow grafts. Longer follow-up is needed to ascertain whether survival differences may occur later.

DISCLOSURE: Dr. Abutalib reported no potential conflicts of interest.

REFERENCES

8. Akhtar S, Montoto S, Boumendil A, et al: Relapsed nodular lymphocyte-predominant Hodgkin lymphoma: High efficacy of high dose chemotherapy and autologous stem cell transplantation. A Study of the Lymphoma Working Party of the European Society for Blood and Marrow Transplantation. 2016 ASH Annual Meeting. Abstract 514. Presented December 4, 2016.

9. Mahindra A, Parmeswaran H, Fraser R, et al: Patients with renal insufficiency and multiple myeloma have similar outcomes after autologous hematopoietic cell transplantation as those without. 2016 ASH Annual Meeting. Abstract 994. Presented December 5, 2016.

10. Wu J, Chen Y, Hageman L, et al: Long-term morbidity and mortality experienced by chronic myeloid leukemia patients after allogeneic hematopoietic cell transplantation: A report from BMTSS-2. 2016 ASH Annual Meeting. Abstract 823. Presented December 5, 2016.

11. Kebriaei P, Anasetti C, Zhang MJ, et al: Comparison of total body irradiation-based with intravenous busulfan-based chemotherapy-only conditioning regimens for myeloablative hematopoietic cell transplantation in adults with acute lymphoblastic leukemia. 2016 ASH Annual Meeting. Abstract 679. Presented December 5, 2016.

12. Krämer I, Stilgenbauer S, Dietrich S, et al: Long-term outcome of allogeneic hematopoietic stem cell transplantation for chronic lymphocytic leukemia: 10-year follow-up of the Gcllsg CLL3X trial. 2016 ASH Annual Meeting. Abstract 682. Presented December 5, 2016.

13. Herrera AF, Song JY, Griffin GK, et al: Double-Hit and double-expressor lymphomas are not associated with an adverse outcome after allogeneic stem cell transplantation. 2016 ASH Annual Meeting. Abstract 830. Presented December 5, 2016.

14. Kumar AJ, Kim S, Hemmer M, et al: Unrelated male donors versus sibling parous female donors: Impact on transplant-related outcomes. 2016 ASH Annual Meeting. Abstract 70. Presented December 3, 2016.

15. Bashey A, Zhang M, McCurdy SR, et al: Comparison of peripheral blood stem cells to bone marrow for T-replete HLA-haploidentical donor transplantation using post-transplant cyclophosphamide. 2016 ASH Annual Meeting. Abstract 683. Presented December 5, 2016.



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