Continuous infusion of intermediate‐dose cytarabine and fludarabine with idarubicin for patients younger than 60 years with resistant acute myeloid leukemia: A prospective,multicenter phase II study

We assessed continuous infusion (CI) of fludarabine and cytarabine (FLAG) plus idarubicin for patients under 60‐years old with resistant acute myeloid leukemia (AML). Induction chemotherapy consisted of idarubicin (12 mg/m² iv infusion over 30 min on Days 1–3), plus fludarabine (30 mg/m2/day) and cytarabine (1,000 mg/m²/day) on Days 1–5 as a 24‐hr CI. G‐CSF was added on Days 1–5. The 29 patients enrolled were of median age 40 years (range, 18–57 years); of these, 8 (27.6%) had primary refractory disease, 19 (65.5%) were in early relapse, and 1 each (3.4%) was in multiple relapse and relapse after SCT. In response to induction, 8 patients (27.6%) achieved CR, 2 (6.9%) achieved CRp, and 19 (65.5%) failed treatment; of the latter, 14 had aplasia, three had an indeterminate course, and two showed resistance. Seven patients remain alive, while two were lost to follow‐up. Nineteen patients died, 14 of infection, one of toxicity during consolidation, three of relapse after SCT, and two of persistent disease. These findings indicate that although CI of FLAG plus idarubicin was effective for eradicating blasts, it carried a high risk of toxicity. Reduced doses are recommended for CI of FLAG plus idarubicin. Am. J. Hematol., 2009. © 2008 Wiley‐Liss, Inc.     

A multicenter,phase II study of maintenance azacitidine in older patients with acute myeloid leukemia in complete remission after induction chemotherapy

Older patients with acute myeloid leukemia (AML) have poor outcomes, with median durations of complete remission lasting less than 1 year. Increased toxicity in older patients limits the delivery of standard consolidation therapies, such as allogeneic stem cell transplant or high‐dose cytarabine. Azacitidine, a nucleoside analog/DNA methyltransferase inhibitor, has demonstrated significant activity and favorable tolerability in patients unable to tolerate intensive induction chemotherapy; however, the role of azacitidine in the maintenance setting has not been fully evaluated. We undertook a pilot study of low‐dose subcutaneous azacitidine [50 mg/(m² day)] for 5 days every 4 weeks) in AML patients ≥60 years of age in first remission following standard induction therapy. The primary objective was to determine the 1‐year disease‐free survival (DFS); secondary objectives were to determine safety and tolerability. We enrolled 24 patients (median age 68, range 62–81 years), the majority of whom received anthracycline‐cytarabine induction regimens. From the time of first complete remission, the estimated 1‐year DFS was 50% and the median overall survival was 20.4 months. Thrombocytopenia and neutropenia were the most common grade 3/4 toxicities (50 and 58%, respectively). In our study population, maintenance therapy with subcutaneous azacitidine was safe and well tolerated. Am. J. Hematol. 90:796–799, 2015. © 2015 Wiley Periodicals, Inc.     

Assessing the efficacy of allogeneic hematopoietic stem cells transplantation (allo‐HSCT) by analyzing survival end points in defined groups of acute myeloid leukemia patients: A retrospective,multicenter Polish Adult Leukemia Group study

The importance of allogeneic hematopoietic stem cell transplantation (allo‐HSCT) for survival outcomes in patients with acute myeloid leukemia (AML) currently remains unclear. The study aimed to compare measures of clinical treatment for patients with AML in CR1 (the first complete remission) with or without being subjected to allo‐HSCT. These consisted of leukemia‐free survival (LFS), overall survival (OS), cumulative incidence of relapse (CIR), and non‐relapse mortality disease (NRM). Subjects were 622 patients, median age of 44, forming part of the prospective, randomized, and multicenter clinical Polish Adult Leukemia Group trials during 1999–2008. The Mantel–Byar approach was used to assess allo‐HSCT on survival endpoints, accounting for a changing transplant status. Undergoing allo‐HSCT significantly improved the LFS and OS for the entire group of patients with AML in CR1, along with the DAC induction subgroup and for the group with unfavorable cytogenetics aged 41–60. The CIR demonstrated that allo‐HSCT reduced the risk of relapse for patients with AML in CR1 and those with an unfavorable cytogenetic risk. In addition, the NRM analysis showed that allo‐HSCT significantly reduced the risk of death unrelated to relapse for the entire group of AML patients in CR1 and aged 41–60. The allo‐HSCT treatment particularly benefitted survival for the AML in CR1 group having an unfavorable cytogenetic prognosis. Am. J. Hematol. 90:904–909, 2015. © 2015 Wiley Periodicals, Inc.     

Salvage therapy for acute myeloid leukemia with fludarabine,cytarabine, and idarubicin with or without gemtuzumab ozogamicin and with concurrent or sequential G‐CSF

The current salvage therapies for relapsed/refractory acute myeloid leukemia (AML) are unsatisfactory. Over the past 7 years, we have used two salvage regimens: fludarabine, cytarabine, and idarubicin with (FLAG‐IM) or without gemtuzumab ozogamicin (GO) (9 mg/m² on Day 8) (FLAG‐I) in relapsed/refractory AML. Three‐quarters of patients also received concurrent G‐CSF. Seventy‐one patients were treated, 23 with FLAG‐I and 48 with FLAG‐IM. The median duration of follow‐up was 30.6 months. The treatment groups were well balanced with median ages of 48 years (range 18–70) and 47 years (range 20–68), unfavorable cytogenetics in 57% and 35%, prior allogeneic stem cell transplant in 43% and 42%, and CR1 duration <1 year in 60% and 67%, respectively, for FLAG‐I and FLAG‐IM. The complete remission (CR) rate in the FLAG‐I group was 39% with an additional 13% achieving a CRp [overall response rate (ORR) 52%]; the CR rate in the FLAG‐IM group was 29% with an additional 27% achieving a CRp (ORR 56%). The median duration of response (DOR; 16.8 vs. 8.3 months), event‐free survival (EFS; 7.4 vs. 4.1 months), and overall survival (OS; 8.8 vs. 5.0 months) trended to favor FLAG‐I over FLAG‐IM. The patients who received G‐CSF concurrent with chemotherapy had superior overall response rate (ORR; 62% vs. 29%, P = 0.026), median EFS (6.2 vs. 3.4 months, P = 0.010), and OS (8.8 vs. 3.9 months, P = 0.004) when compared with those who sequentially received G‐CSF and chemotherapy, regardless of chemotherapy regimen. The addition of GO, at this dose and schedule, to FLAG‐I failed to improve the outcomes in patients with relapsed/refractory AML. The patients who received G‐CSF concurrently with chemotherapy had improved outcomes. Am. J. Hematol., 2009. © 2009 Wiley‐Liss, Inc.     

A prognostic model for survival after salvage treatment with FLAG‐Ida +/− gemtuzumab‐ozogamicine in adult patients with refractory/relapsed acute myeloid leukaemia

The combination of fludarabine, cytarabine, idarubicin, and granulocyte colony‐stimulating factor (FLAG‐Ida) is widely used in relapsed/refractory acute myeloid leukaemia (AML). We retrospectively analysed the results of 259 adult AML patients treated as first salvage with FLAG‐Ida or FLAG‐Ida plus Gentuzumab‐Ozogamicin (FLAGO‐Ida) of the Programa Español de Tratamientos en Hematología (PETHEMA) database, developing a prognostic score system of survival in this setting (SALFLAGE score). Overall, 221 patients received FLAG‐Ida and 38 FLAGO‐Ida; 92 were older than 60 years. The complete remission (CR)/CR with incomplete blood count recovery (CRi) rate was 51%, with 9% of induction deaths. Three covariates were associated with lower CR/CRi: high‐risk cytogenetics and t(8;21) at diagnosis, no previous allogeneic stem cell transplantation (allo‐SCT) and relapse‐free interval <1 year. Allo‐SCT was performed in second CR in 60 patients (23%). The median overall survival (OS) of the entire cohort was 0·7 years, with 22% OS at 5‐years. Four independent variables were used to construct the score: cytogenetics, FLT3‐internal tandem duplication, length of relapse‐free interval and previous allo‐SCT. Using this stratification system, three groups were defined: favourable (26% of patients), intermediate (29%) and poor‐risk (45%), with an expected 5‐year OS of 52%, 26% and 7%, respectively. The SALFLAGE score discriminated a subset of patients with an acceptable long‐term outcome using FLAG‐Ida/FLAGO‐Ida regimen. The results of this retrospective analysis should be validated in independent external cohorts.     

Phase II clinical trial for the evaluation of bortezomib within the reduced intensity conditioning regimen (RIC) and post‐allogeneic transplantation for high‐risk myeloma patients

The current study was designed to assess the safety and efficacy of bortezomib in combination with fludarabine and melphalan as reduced intensity conditioning before allogeneic stem cell transplantation in patients with high risk multiple myeloma. Sixteen patients were evaluable. The median number of previous line of treatment was 3; all patients had relapsed following a prior autograft and 13 had previously received bortezomib. Fifteen of them either remained stable or improved disease status at day +100 post‐transplant, including 11 patients with active disease. More specifically, nine patients (56%) and five patients (31%) reached complete remission and partial response, respectively. 25% developed grade III acute graft‐versus‐host disease. The cumulative incidence of non‐relapse mortality, relapse and overall survival were 25%, 54% and 41%, respectively, at 3 years. Regarding the non‐haematological toxicity (grade>2), two patients developed peripheral neuropathy, two patients liver toxicity and 1 pulmonary toxicity early post‐transplant. The haematological toxicity was only observed during the first three cycles mostly related to low haemoglobin and platelet levels. The current trial is the first one evaluating the safety and efficacy of bortezomib as part of a reduced intensity conditioning regimen among patients with high risk multiple myeloma.     

Inferior outcome after allogeneic transplant in first remission in high‐risk AML patients who required more than two cycles of induction therapy

While some patients with high‐risk acute myeloid leukemia (AML) require one or two cycles of induction chemotherapy to achieve a complete remission (CR), others require more than two cycles. We examined the outcomes of patients with high‐risk AML who received allogeneic HPC transplant in CR1. Forty five consecutive high‐risk AML patients in CR1 were included. All 45 patients had adverse cytogenetics, FLT 3 mutations, or secondary AML. Group A patients (n = 33) received one or two cycles, and Group B (n = 12) three or more cycles of induction chemotherapy. The patients were comparable in age, sex, white cell count at presentation, and time from diagnosis and from last chemotherapy to transplant. The 100‐day mortality rate was higher in Group B patients (50% vs. 9%, P = 0.006). They had a higher non‐relapse mortality (33% vs. 6%, P = 0.035) and a longer length of hospital stay from the day of stem cell infusion (median 21 vs. 20, P = 0.02; third quartile 22 vs. 28, P = 0.02). There was also a trend toward inferior event‐free survival and overall survival. High‐risk AML patients undergoing allogeneic transplant in CR1 after three or more cycles of induction chemotherapy have an inferior outcome and higher mortality when compared to those who only needed one or two cycles of induction chemotherapy. Novel strategies are needed to reduce the transplant‐related mortality in high‐risk AML patients needing more than two cycles of induction chemotherapy prior to allogeneic transplant in CR1. Am. J. Hematol. 90:715–718, 2015. © 2015 Wiley Periodicals, Inc.     

De novo acute myeloid leukemia with multilineage dysplasia: treatment results and prognostic evaluation from a series of 44 patients treated with fludarabine,cytarabine and G-CSF (FLAG)

OBJECTIVES: To evaluate therapeutic results and prognostic factors from a series of 44 patients affected by de novo acute myeloid leukemia with multilineage dysplasia (MD-AML), treated with the combination of fludarabine, cytarabine and G-CSF (FLAG). METHODS: Forty-four patients with de novo MD-AML were treated with the FLAG regimen. The median age was 61 yr (range 31-75 yr). Induction therapy consisted of the FLAG regimen; consolidation included idarubicin plus cytarabine. Patients with a compatible donor and aged less than 55 yr were programmed to receive allogeneic bone marrow transplantation (BMT), while in those without a donor and aged less than 65 yr autologous transplantation with peripheral blood stem cells mobilized by a consolidation regimen plus G-CSF was planned. Bone marrow harvest was performed in poor mobilizers. RESULTS: Complete remission (CR) was achieved in 28 out of 44 patients (64%). Death in induction occurred in four patients (9%), while 12 patients (27%) were resistant to FLAG. Toxicity of consolidation was negligible. Most patients aged less than 60 yr and achieving CR were eligible for transplantation procedures, the main reason of exclusion being early relapse. Median overall survival and disease free survival were 16 and 22 months, respectively. Unfavorable cytogenetics was the only parameter significantly related to inferior clinical outcome following multivariate analysis. CONCLUSION: Multilineage dysplasia per se is not an adverse prognostic factor in AML patients treated with the FLAG regimen. Favorable results are obtained in patients with intermediate karyotype, while in those with adverse cytogenetics new approaches are clearly needed. The toxicity of the regimen is also acceptable in the elderly, and following induction/consolidation, most patients may be submitted to transplantation procedures.     

Allogeneic hematopoietic stem cell transplantation for adult patients with mixed phenotype acute leukemia: results of a matched‐pair analysis

Adult patients with mixed phenotype acute leukemia (MPAL) have a poor prognosis, and the therapeutic role of allogeneic stem cell transplantation (allo‐SCT) for MPAL remains to be elucidated. Thus, we retrospectively assessed the efficacy of allo‐SCT for MPAL. Eighteen patients with MPAL were identified from the transplant outcome database of Kanto Study Group for Cell Therapy (KSGCT). We also selected 215 patients with acute myeloid leukemia (AML) and acute lymphoblastic leukemia (ALL) as control cohorts using an optimal matching method. The 5‐yr overall survival (OS) rate of patients with MPAL was 48.1%, and patients in remission at the time of transplant showed significantly better survival than those not in remission (5‐yr OS: 71.8% vs. 0%, P = 0.001). No significant differences were seen in OS when stratifying patients according to immunophenotype, cytogenetic abnormalities, or the type of induction therapy. The 5‐yr OS rate of patients with MPAL was not significantly different compared with AML control patients (48.1% vs. 48.1%; P = 0.855) or ALL control patients (48.1% vs. 37.8%; P = 0.426). These results suggested that allo‐SCT is an effective treatment for MPAL, especially early in the disease course, and innovative transplant approaches are warranted to improve the transplant outcome of patients with MPAL who are not in remission.     

Gemtuzumab ozogamicin with fludarabine,cytarabine, and granulocyte colony stimulating factor (FLAG‐GO) as front‐line regimen in patients with core binding factor acute myelogenous leukemia

Despite being considered “good‐risk” acute myelogenous leukemia (AML), long term outcomes in core binding factor (CBF) AML suggest room for improvement. We report on a regimen consisting of fludarabine, cytarabine, granulocyte colony stimulating factor, and low dose gemtuzumab ozogamicin (FLAG‐GO) as front‐line therapy of patients with CBF AML. Forty‐five patients were enrolled (median age 48 years). Remission rate was 95% with 5% induction deaths. The overall survival (OS) and relapse free survival (RFS) probability at 3 years are 78% and 85%, respectively. FLAG‐GO regimen results in high rates of RFS and OS in CBF AML. Our data along with recent data from several large groups strongly argues in favor of incorporation of gemtuzumab ozogamicin in frontline regimens for CBF AML. Am. J. Hematol. 89:964–968, 2014. © 2014 Wiley Periodicals, Inc.     

Results of risk‐adapted therapy in acute myeloid leukaemia. A long‐term population‐based follow‐up study

In 1997–2003, a protocol for treatment of acute myeloid leukaemia (AML) (except promyelocytic leukaemia) was activated in four Swedish health care regions covering 50% of the national population. Based on cytogenetics and clinical findings, patients aged 18–60 yr were assigned to one of three risk groups. In this report we account for the long‐term clinical outcome of enrolled patients. Patients received idarubicin and cytarabine in standard doses as induction therapy and consolidation courses included high‐dose cytarabine. Allogeneic stem cell transplantation (allo‐SCT) from an human leucocyte antigen‐identical sibling was recommended in standard and poor‐risk patients, whereas unrelated donor transplant was reserved for poor‐risk patients. Autologous (auto‐SCT) was optional for standard or poor risk patients not eligible for allo‐SCT. Two hundred seventy‐nine patients with de novo or secondary (9%) AML, median age 51 (18–60) yr, corresponding to 77% of all patients in the population, were included. Twenty (7%) patients were assigned to the good risk group, whereas 150 (54%) and 109 patients (39%) were assigned to standard‐ and poor‐risk groups, respectively. Induction failures accounted for 55 patients; 16 early deaths eight of whom had white blood cell (WBC) >100 at diagnosis, and 39 refractory disease. Thus, complete remission (CR) rate was 80%. At study closure, the median follow‐up time of living patients was 90 months. Median survival time from diagnosis in the whole group was 27 months and 4‐yr overall survival (OS) rate was 44%. In good, standard, and poor risk groups, 4‐yr OS rates were 60, 57 and 24%, respectively. Median relapse‐free survival (RFS) time in CR1 was 25 months and RFS at 4 yr was 44%. Four‐year RFS rates were significantly (P < 0.001) different between the three risk groups; 64% in good risk, 51% in standard risk and 27% in poor risk patients. One hundred‐ten transplantations were performed in CR1; 74 allo‐SCT (50 sibling, 24 unrelated donor), and 36 auto‐SCT. Non‐relapse mortality was 16% for allo‐SCT patients. Outcome after relapse was poor with median time to death 163 d and 4‐yr survival rate 17%. Three conclusions were: (i) these data reflect treatment results in a minimally selected population‐based cohort of adult AML patients <60 yr old; (ii) a risk‐adapted therapy aiming at early allogeneic SCT in patients with a high risk of relapse is hampered by induction deaths, refractory disease, and early relapses; and (iii) high WBC count at diagnosis is confirmed as a strong risk factor for early death but not for relapse.     

Fludarabine,cytarabine, and G-CSF (FLAG) for the treatment of poor risk acute myeloid leukemia

Thirty-eight patients with primary resistant or relapsing acute myeloid leukemia (AML) were treated with fludarabine, cytarabine and granulocyte colony-stimulating factor (FLAG). Median age was 41 (range 11–70). Sixteen patients had AML that was primary resistant to induction treatment, while 22 were relapsed, 11 after autologous bone marrow transplant (AuBMT), 8 less than 6 months from complete remission (CR) achievement, and 3 were second relapse from chemotherapy alone. Overall, 21 of 38 patients (55%) obtained CR. Age, sex, length of CR, and interval between autoBMT and FLAG administration did not significantly influence the CR rate. On the contrary, a normal karyotype at diagnosis was significantly related to a better outcome. There were 4 induction deaths (10%), due to fungal infection in 2 patients and hemorrhagic complications in the remaining two. All patients experienced profound cytopenia. Median time to neutrophil (>500/μl) recovery was 21 days, while a platelet count >20,000/μl was reached after 23 days. The median period of hospitalization was 31 days. The nonhematological toxicity was mild, mainly consisting of mucositis. There were 17 documented infections and 17 episodes of fever of unknown origin. Following CR achievement, 6 patients received autoBMT, 3 alloBMT, 2 high-dose arabinosil-cytosine, and 2 are on a waiting list for transplantation procedure. We conclude that FLAG is an effective and well-tolerated regimen for refractory or recurrent AML, mainly useful for patients to be admitted to bone marrow transplantation. Am. J. Hematol. 58:105–109, 1998. © 1998 Wiley-Liss, Inc.     

Improved outcome with hematopoietic stem cell transplantation in a poor prognostic subgroup of patients with mixed‐lineage‐leukemia‐rearranged acute leukemia: Results from a prospective,multi‐center study

The purpose of this study is to define the role for allogeneic hematopoietic stem cell transplantation (allo‐HSCT) in mixed‐lineage‐leukemia (MLL)‐rearranged acute leukemia, which is now poorly understood. A prospective, multi‐center cohort study to determine whether allo‐HSCT could decrease relapse rates and improve long‐term survival of MLL+ leukemia patients was performed. Fifty‐six consecutive patients diagnosed with MLL–rearranged acute leukemia undergoing allo‐HSCT from two transplant centers in China were enrolled between October 2007 and October 2012. The trial was registered at www.chictr.org as # ChiCTR‐ONC‐12002739. The incidences of grades II to IV acute graft versus host disease (aGVHD) and of grades III and IV aGVHD were 28.8% (CI, 16.87–40.8%), and 14.2% (CI, 5.4–23.0%), respectively. The cumulative incidences for chronic GVHD (cGVHD) at 2 years after HSCT were 35.2% (CI, 21.2–49.2%). Up to April 30, 2013, 12 patients had relapsed and 11 died from relapse, and 37 patients were still alive without disease recurrence. The relapse and NRM rates at 3 years were 25.3% (CI, 12.7–37.9%) and 18.0% (CI, 2.6–33.4%), respectively. The probalities of overall survival and leukemia free survival were 61.8% (CI, 46.0–77.6%) and 56.3% (CI, 38.1–74.5%) at 3 years, respectively. Patients transplanted during their hematological first complete remission (CR1) had a lower relapse rate (17.9% vs. 48.1%, P = 0.03) compared with patients transplanted beyond CR1. The median overall survival for the 29 patients not receiving allo‐HSCT during the study period was 145 days from diagnosis. This study showed that allo‐HSCT could be a valuable treatment choice for MLL+ acute leukemia. Am. J. Hematol. 89:130–136, 2014. © 2013 Wiley Periodicals, Inc.     

Allogeneic hematopoietic stem cell transplantation for T‐prolymphocytic leukemia: a report from the French society for stem cell transplantation (SFGM‐TC)

T‐prolymphocytic leukemia (T‐PLL), a rare aggressive mature T‐cell disorder, remains frequently resistant to conventional chemotherapy. Studies have suggested that allogeneic hematopoietic stem cell transplantation (HSCT) might possibly serve to consolidate the response to initial chemotherapy. The current report summarizes the outcome of 27 T‐PLL cases identified in the registry in French Society for stem cell transplantation (SFGM‐TC). Prior to HSCT, 14 patients were in complete remission (CR), 10 in partial response, three refractory, or in progression. Following HSCT, 21 patients achieved CR as best response. With a median follow‐up for surviving patients of 33 (range, 6–103) months, 10 patients are still alive in continuous CR. Overall survival and progression‐free survival estimates at 3 yr were 36% (95% CI: 17–54%) and 26% (95% CI: 14–45%), respectively. The relapse incidence after HSCT was 47% occurring at a median of 11.7 (range, 2–24) months. Overall cumulative incidence of transplant‐related mortality was 31% at 3 yr. These results suggest that HSCT may allow long‐term survival in patients with T‐PLL following induction treatment; however, it is associated with a significant rate of toxicity.     

FLAMSA reduced‐intensity conditioning is equally effective in AML patients with primary induction failure as well as in first or second complete remission

Reduced‐intensity conditioning regimens have demonstrated lower toxicity but increased relapse rates in the context of allogeneic hematopoietic stem cell transplantation (aSCT) for patients with acute myelogenous leukemia (AML). The FLAMSA‐ reduced‐intensity conditioning (RIC) regimen, combining a cytoreductive and a transplant‐conditioning part, has been described to be efficacious in patients with refractory disease. We retrospectively analyzed clinical data of 130 patients with AML after aSCT following FLAMSA RIC at our center. The median follow‐up was 37 (10–125) months. The 4‐yr overall and disease‐free survival rates of the whole cohort were 45% and 40%. Cumulative incidence of relapse was 29%, 35%, and 40% at 1, 2, and 4 yr. There were no significant differences regarding overall and disease‐free survival for patients transplanted in CR1, CR2, or primary induction failure (PIF). Patients with refractory disease after salvage therapy had significantly lower disease‐free and overall survival (OS). Disease‐free and OS rates were also significantly decreased in patients with 10% or more BLASTS at transplant. non‐relapse mortality was 15%, 19%, and 20% at 1, 2, and 4 yr and similar in all cohorts. These data underscore the potency of the FLAMSA RIC regimen for patients with AML especially with PIF. The decision for re‐induction therapy prior to aSCT in relapsed patients has to be weighed against the potential toxicity of this approach and might be influenced by the amount of leukemic BLASTS present. Only randomised trials will answer this important question.     

Comparison of umbilical cord blood allogeneic stem cell transplantation vs. auto‐SCT for adult acute myeloid leukemia patients in second complete remission at transplant: a retrospective study on behalf of the SFGM‐TC

This retrospective study considered the outcomes of 181 patients with acute myeloid leukemia (AML) transplanted in second complete remission (CR2) between January 2005 and April 2012 and who received either a myeloablative autologous stem cell transplant (Auto‐SCT; n = 82; median age: 48 years; median follow‐up: 45 months) or an umbilical cord blood (UCB) allogeneic SCT (n = 99, median age: 46 years; median follow‐up: 36 months; conditioning regimens: myeloablative n = 21, reduced n = 78; single unit n = 37, double units n = 62). Although the Auto group showed a significant better prognostic profile at transplant, with longer median interval between diagnosis and time of graft, higher incidence of good‐risk cytogenetics and lower number of previously transplanted patients, 3‐year OS and LFS were similar between both groups (Auto: 59 ± 6% vs. 50 ± 6%, P = 0.45; and 57 ± 6% vs. 46 ± 6%, P = 0.37). In multivariate analysis, UCB allo‐SCT was associated with lower relapse incidence (HR: 0.3, 95% CI: 0.11–0.82, P = 0.02), but higher non‐relapse mortality (NRM) (HR: 4.16; 95% CI: 1.46–11.9, P = 0.008). Results from this large study suggest that UCB allo‐SCT provides better disease control than auto‐SCT, which is especially important in the setting of high‐risk disease. However, this disease control advantage is counterbalanced by higher toxicity, highlighting the need for novel approaches aiming to decrease NRM after UCB allo‐SCT.     

Brentuximab vedotin prior to allogeneic stem cell transplantation in Hodgkin lymphoma: a report from the EBMT Lymphoma Working Party

Brentuximab vedotin (BV) is an anti‐CD30 antibody‐drug conjugate. Preliminary data suggest that BV might improve outcomes after allogeneic stem cell transplantation (SCT) for Hodgkin lymphoma (HL) when used as pre‐transplant salvage therapy. Between 2010 and 2014, 428 adult patients underwent an allogeneic SCT for classical HL at participating centres of the European Society for Blood and Marrow Transplantation. We compared the outcomes of 210 patients who received BV prior to allogeneic SCT with that of 218 patients who did not receive BV. The median follow‐up for survivors was 41 months. Patients in the BV group were more heavily pre‐treated (median pre‐allograft treatment lines: 4 vs. 3). The two groups were comparable in terms of disease status, performance status, comorbidities, prior autologous SCT, type of donor, conditioning and in vivo T cell depletion. In multivariate analysis, pre‐allograft BV had no impact on acute graft‐versus‐host disease (GVHD), non‐relapse mortality, cumulative incidence of relapse, progression‐free survival or overall survival (OS), but significantly reduced the risk of chronic GVHD (hazard ratio = 0·64; 95% confidence interval = 0·45–0·92; P < 0·02). Older age, poor performance status, use of pre‐transplant radiotherapy and active disease at SCT adversely affected OS. Patients allografted for HL after prior exposure to BV do not have a superior outcome after allogeneic SCT except for a lower risk of chronic GVHD. However, BV may improve the outlook of allogeneic SCT by helping otherwise refractory patients to achieve a more favourable disease status, facilitating allotransplant success.     

Second allogeneic hematopoietic stem cell transplantation as treatment for leukemia relapsing following a first transplant

We report 27 patients with relapsed acute or chronic leukemia who underwent a second hematopoietic stem cell transplant (HSCT) from a related or unrelated donor. Seventeen patients were diagnosed with acute myelogenous leukemia (AML), six with acute lymphocytic leukemia (ALL) and four with chronic myeloid leukemia (CML). Ages ranged from 22 to 49 years (median 37); 13 patients were female and 14 male. Relapse was diagnosed between 1 and 45 months after the first HSCT. Sixteen patients who relapsed had received an autologous transplant initially and 11 an allogeneic transplant. Ten patients relapsed within 6 months and 17 patients later than 6 months. Chemotherapy was used as reinduction for relapse after HSCT in 16 patients who had received an autologous transplant and in three who had received an allogeneic transplant, since the latter did not respond to reduction of immunosuppression to induce a graft-versus-leukemia (GVL) reaction. Five of these 19 patients (26%) achieved complete remission (CR), seven patients did not respond to chemotherapy and seven achieved a partial remission (PR). The stem cell source for the second HSCT included bone marrow (n = 12) and PBSC (n = 4) from genotypically identical unrelated donors, PBSC (n = 7) and bone marrow (n = 3) from related donors. Currently eight of the 27 patients are alive and disease-free after the second HSCT. One patient is alive and disease-free after two allogeneic transplants (day +1538), eight patients, who relapsed after an autologous transplant followed by an allogeneic transplant (days +248 to +1140), acute myeloid leukaemia (n = 6) and chronic myeloid leukemia (n = 2) are alive and disease-free. The overall disease-free survival is 30% (8/27). The overall disease-free survival of autologous transplant patients subsequently undergoing an allogeneic transplant is 43% (P = 0.049). It is suggested that a second HSCT is possible for patients with leukemia relapse following the first autologous transplant. A second transplant might also be offered to patients relapsing after the first allogeneic HSCT. Bone Marrow Transplantation (2000) 25, 41-45.     

Long-term outcome of adult acute leukemia patients who are alive and well 2 years after autologous blood or marrow transplantation.

We studied the long-term outcome of 87 adults with acute leukemia (age 15-59 years at transplant, median 27; 44 myeloid, 42 lymphoblastic, one biphenotypic) who were alive in continuous remission 2 years after a marrow (n = 74) or blood stem cell (n = 13) autograft. Nine relapsed 25-50 months (median 38) after transplantation. Five relapses were straightforward with no karyotypic or morphologic evolution of the original disease. Four recurrences were unusual, with development of myelodysplasia (n = 3) or myeloproliferative disease (n = 1). Five patients died of relapsed disease and four are still alive. Two patients died of complications related to the transplant, and one of ischemic heart disease. Seventy-nine patients (91%) are alive in remission 24-149 months (median 67) after transplantation (75 in continuous remission and four after further therapy) with Karnofsky scores of 80-100% (median 100%). The 8-year probabilities of survival, toxic death, and relapse (from the 2-year mark) are 89%, 3% and 12%. Eleven (12%) survivors had creatinine levels of >110 micromol/l (one more than double), and 14 (16%) had bilirubin levels of >17 mmol/l (one more than double) at the last follow-up. None of the following factors was found to be predictive for survival, non-relapse death, or relapse from the 2-year mark in multivariate analysis: age, sex, type of leukemia, disease stage, diagnosis, conditioning, origin of cells, and nucleated cell dose. We conclude that adult patients with acute leukemia who are alive and well 2 years following an autograft have a high probability of being cured, and the incidence of long-term liver and kidney dysfunction measured by serum bilirubin and creatinine is low.