Brentuximab vedotin induces an overall response rate of 75% in patients with relapsed/refractory Hodgkin lymphoma, but its impact on future allogeneic transplantation (allo-HCT) is not known. We retrospectively examined the records of 18 patients with relapsed/refractory Hodgkin lymphoma who were treated on brentuximab vedotin clinical trials to evaluate the efficacy and safety of subsequent reduced-intensity allo-HCT. Seventeen patients had previous autologous transplant; 6 were in complete remission, and 8 were in partial remission before allo-HCT with 12 grafts from unrelated or mismatched donors. The 1-year overall survival was 100%, progression-free survival was 92.3%, and nonrelapse mortality was 0% (median follow-up, 14 months). The incidence of acute GVHD was 27.8% and chronic GVHD was 56.3%. Brentuximab vedotin before reduced-intensity allo-HCT does not appear to adversely affect engraftment, GVHD, or survival and may provide sufficient disease control to enable reduced-intensity allo-HCT. (Blood. 2012;119(26):6379-6381)

Therapy-related acute lymphoblastic leukemia remains poorly defined due to a lack of large data sets recognizing the defining characteristics of this entity. We reviewed all consecutive cases of adult acute lymphoblastic leukemia treated at our institution between 2000 and 2017 and identified therapy-related cases - defined as acute lymphoblastic leukemia preceded by prior exposure to cytotoxic chemotherapy and/or radiation. Of 1022 patients with acute lymphoblastic leukemia, 93 (9.1%) were classified as therapy-related. The median latency for therapy-related acute lymphoblastic leukemia onset was 6.8 years from original diagnosis, and this was shorter for patients carrying the MLL gene rearrangement compared to those with other cytogenetics. When compared to de novo acute lymphoblastic leukemia, therapy-related patients were older (P<0.01), more often female (P<0.01), and had more MLL gene rearrangement (P<0.0001) and chromosomes 5/7 aberrations (P=0.02). Although therapy-related acute lymphoblastic leukemia was associated with inferior 2-year overall survival compared to de novo cases (46.0% vs. 68.1%, P=0.001), prior exposure to cytotoxic therapy (therapy-related) did not independently impact survival in multivariate analysis (HR=1.32; 95% CI: 0.97–1.80, P=0.08). There was no survival difference (2-year = 53.4% vs. 58.9%, P=0.68) between the two groups in patients who received allogenic hematopoietic cell transplantation. In conclusion, therapy-related acute lymphoblastic leukemia represents a significant proportion of adult acute lymphoblastic leukemia diagnoses, and a subset of cases carry clinical and cytogenetic abnormalities similar to therapy-related myeloid neoplasms. Although survival of therapy-related acute lymphoblastic leukemia was inferior to de novo cases, allogeneic hematopoietic cell transplantation outcomes were comparable for the two entities.

Current conditioning regimens provide insufficient disease control in relapsed/refractory acute leukemia (AL) patients undergoing hematopoietic stem cell transplantation (HSCT) with active disease. Intensification of chemotherapy and/or total body irradiation (TBI) is not feasible because of excessive toxicity. Total marrow and lymphoid irradiation (TMLI) allows for precise delivery and increased intensity treatment via sculpting radiation to sites with high disease burden or high risk for disease involvement, while sparing normal tissue. We conducted a phase I trial in 51 patients (age: 16–57 years) with relapsed/refractory AL undergoing HSCT (matched related, matched unrelated, or one-allele mismatched unrelated) with active disease, combining escalating doses of TMLI (range 1200–2000 cGy) with cyclophosphamide (CY) and etoposide (VP16). The maximum tolerated dose was declared at 2000 cGy since TMLI simulation studies indicated that >2000 cGy might deliver doses toxic for normal organs at or exceeding those delivered by standard TBI. The post transplant non-relapse mortality (NRM) rate was only 3.9% (95% CI: 0.7–12.0) at day +100 and 8.1% (95% CI: 2.5–18.0) at one year. The cumulative incidence of grade II–IV acute GVHD was 43.1% (95% CI: 29.2–56.3) and for grade III–IV was 13.7% (95% CI: 6.9–27.3). The day +30 complete remission rate for all patients was 88% and was 100% for those treated at 2000 cGy. The overall one-year survival was 55.5% (95% CI: 40.7–68.1). The TMLI/CY/VP16 conditioning regimen is well tolerated at TMLI doses up to 2000 cGy with a low 100 day and 1 year NRM rate and no increased risk of GVHD with higher doses of radiation.

This phase 2 trial evaluated PET-adapted nivolumab (Nivo) alone or in combination with ifosfamide, carboplatin, and etoposide (NICE) as first salvage therapy and bridge to autologous hematopoietic cell transplantation (AHCT) in relapsed/refractory (RR) classical Hodgkin lymphoma (cHL). Patients with RR cHL received 240mg Nivo every 2 weeks for up to 6 cycles (C). Patients in complete response (CR) after C6 proceeded to AHCT, while patients with progressive disease (PD) at any point or not in CR after C6 received NICE for 2 cycles. The primary endpoint was CR rate per the 2014 Lugano classification at completion of protocol therapy. 43 patients were evaluable for toxicity; 42 were evaluable for response. 34 patients received Nivo alone and 9 patients received Nivo+NICE. No unexpected toxicities were observed after Nivo or NICE. After Nivo, the overall response rate (ORR) was 81% and the CR rate was 71%. Among the 9 patients who received NICE, all responded with 8 (89%) achieving CR. At the end of all protocol therapy, the ORR and CR rates were 93% and 91%. Thirty-three patients were bridged directly to AHCT, including 26 after Nivo alone. The 2-year progression-free survival (PFS) and overall survival in all treated patients (n=43) were 72% (95%CI:56-83) and 95% (95%CI:82-99), respectively. Among the 33 patients who bridged directly to AHCT after protocol therapy, the 2-year PFS was 94% (95%CI:78-98). PET-adapted sequential salvage therapy with Nivo or Nivo+NICE was well-tolerated and effective, resulting in a high CR rate and bridging most patients to AHCT without chemotherapy. This Clinical Trial is registered under NCT03016871

Acute lymphoblastic leukemia (ALL) with high-risk features has a poor prognosis in adults despite aggressive chemotherapy. Reduced-intensity conditioning (RIC) is a lower toxicity alternative for high-risk patients requiring hematopoietic cell transplantation (HCT), however it has not been widely used for ALL. We conducted a retrospective study of 24 high-risk adult ALL patients who received an RIC regimen of fludarabine/melphalan prior to allogeneic peripheral blood stem cell transplant between 6/14/02 and 6/15/07 at City of Hope. Indications for the RIC regimen were: 1) age 50 or older (42%), 2) compromised organ function (54%), or 3) recipient of a previous HCT (37.5%). Patients had a median age of 47.5 years and the median follow-up was 28.5 months for living patients. Both overall survival and disease-free survival at two years was 61.5%. Relapse incidence was 21.1% and non-relapse mortality was 21.5% at two years. cGVHD developed in 86% of evaluable patients. In this series, no significant correlations were made between outcomes and patient age, presence of Philadelphia chromosome, relatedness of donor source or prior HCT. These high survival rates for high-risk ALL patients following RIC HCT may offer a promising option for patients not eligible for a standard myeloablative transplant.

Second-line BV is an effective bridge to AHCT that produces responses of sufficient depth to provide durable remission in conjunction with AHCT (clinicaltrials.gov: NCT01393717).

Anal melanoma is an aggressive tumor with a predilection for early infiltration and distant spread, resulting in poor overall survival. Because anal melanoma is rare, only small case series are reported in the literature, making it difficult to draw conclusions about optimal treatment and outcome. The Surveillance, Epidemiology, and End Results database was used to identify patients with anal melanomas from 1973 to 2001. In addition to demographics, disease extent at presentation, treatment administered, overall survival, and survival by decade of diagnosis were collected. A total of 126 patients with a mean age of 69.2 years was diagnosed with anal melanoma. Sixty-one per cent were female. Median follow-up was 22.5 months. Median survival was 10 months for those with distant disease, 13 months for patients with regional spread, and 34 months for patients with local disease (P = 0.0001). Five-year survival was 32 per cent, 17 per cent, and 0 per cent for patients presenting with local, regional, and distant disease, respectively (P = 0.0001). Neither age at diagnosis, operation performed, nor use of radiation significantly affected survival. Anal melanoma remains an uncommon but lethal disease. Extent of disease correlates with overall survival. Survival is improving, but the use and extent of operation are not associated with improved overall survival.

Purpose Randomized trials comparing autologous stem cell transplant (ASCT) to conventional chemotherapy have demonstrated superior survival among HIV negative ASCT patients with relapsed non-Hodgkin lymphoma (NHL). Recent trials explored the feasibility of ASCT in the HIV setting. While these studies have shown that ASCT in HIV positive NHL patients (HIVpos-NHL) is well tolerated, the impact of HIV infection on long-term transplant outcome is not well characterized. Ongoing comparison of long-term survival following ASCT in HIVpos-NHL patients and HIVneg-NHL patients will allow investigators to explore whether there should be inclusion of HIVpos-NHL patients in ASCT trials. Patients and Methods To study long-term outcome we conducted a single institution matched case-control study in HIVpos-NHL patients (cases) and HIVneg-NHL patients (controls). Twenty-nine patients with HIVpos-NHL were matched with HIVneg-NHL controls on gender, time to ASCT, year of transplant, histology, age, disease status, number prior regimens, and conditioning regimen. Results Non-relapse mortality was similar: 11% (95%CI: 4–28%) in HIVpos-NHL patients and 4% (95%CI: 1–25%) in HIVneg-NHL controls (p=0.18). Two year DFS for the HIVpos-NHL patients was 76% (95%CI: 62–85%) and 56% (95%CI: 45–66%) for the HIVneg-NHL controls (p=0.33). OS was also similar; the two-year point estimates were 75% (95%CI: 61–85%) and 75% (95%CI: 60–85%) respectively (p=0.93), despite inclusion of more poor risk HIVpos-NHL patients. Conclusion These results provide further evidence that HIV status does not affect the long-term outcome of ASCT for NHL and therefore HIV status alone should no longer exclude these patients from transplant clinical trials.