Sequential vs myeloablative vs reduced intensity conditioning for patients with myelodysplastic syndromes with an excess of blasts at time of allogeneic haematopoietic cell transplantation: a retrospective study by the chronic malignancies working party of the EBMT.

The optimal conditioning for patients with higher risk MDS receiving potentially curative allogeneic haematopoietic stem cell transplant(allo-HCT) remains to be defined. This is particularly the case for patients with excess of blasts at time of allo-HCT. Sequential (Seq) conditioning, whereby chemotherapy is followed rapidly by transplant conditioning, offers an opportunity to decrease disease burden, potentially improving outcomes allo-HCT outcomes. Herein we present the only analysis comparing Seq to myeloablative (MAC) and reduced intensity conditioning (RIC) specifically focussed on MDS patients with excess of blasts at allo-HCT. 303 patients were identified in the EBMT registry, receiving RIC (n = 158), Seq (n = 105), and MAC (n = 40). Median follow-up was 67.2 months and median age at allo-HCT was 59.5 years (IQR 53.5-65.6). For the entire cohort, 3 y overall survival (OS) was 50% (95% CI 45-56%) and relapse free survival (RFS) 45% (95% CI 40-51%). No significant differences in OS (log-rank p = 0.13) and RFS (log-rank p = 0.18) were observed between conditioning protocols. On multivariable analysis, lower performance status, worse IPSS-R cytogenetics, sibling donor (compared to 8/8 MUD) and ≥20% blasts at allo-HCT were associated with worse outcomes. In conclusion, the Seq protocol did little to influence the outcome in this high-risk group of patients, with outcomes mostly determined by baseline disease risk and patient characteristics such as performance status.

EBMT prospective observational study on allogeneic hematopoietic stem cell transplantation in T-prolymphocytic leukemia (T-PLL).

Preliminary data suggest that allogeneic stem cell transplantation (allo-SCT) may be effective in T-prolymphocytic leukemia (T-PLL). The purpose of the present observational study was to assess the outcome of allo-SCT in patients aged 65 years or younger with a centrally confirmed diagnosis of T-PLL. Patients were consecutively registered with the EBMT at the time of transplantation and followed by routine EBMT monitoring but with an extended dataset. Between 2007 and 2012, 37 evaluable patients (median age 56 years) were accrued. Pre-treatment contained alemtuzumab in 95% of patients. Sixty-two percent were in complete remission (CR) at the time of allo-SCT. Conditioning contained total body irradiation with 6 Gy or more (TBI6) in 30% of patients. With a median follow-up of 50 months, the 4-year non-relapse mortality, relapse incidence, progression-free (PFS) and overall survival were 32, 38, 30 and 42%, respectively. By univariate analysis, TBI6 in the conditioning was the only significant predictor for a low relapse risk, and an interval between diagnosis and allo-SCT of more than 12 months was associated with a lower NRM. This study confirms for the first time prospectively that allo-SCT can provide long-term disease control in a sizable albeit limited proportion of patients with T-PLL.

Influence of Clonal Plasma Cell Contamination of Peripheral Blood Stem Cell Autografts on Progression and Survival in Multiple Myeloma Patients After Autologous Peripheral Blood Stem Cell Transplantation in Long-term Observation.

BACKGROUND: High-dose chemotherapy followed by autologous peripheral blood stem cell transplantation (auto-PBSCT) remains the mainstay of treatment of eligible patients diagnosed multiple myeloma. The role of clonal plasma cell (CPC) contamination was found as a reason for relapse, but results in terms of survival, progression, and purging were ambiguous. Therefore, the aim of the study was to explore the influence of CPC contamination in the autograft on survival and progression after auto-PBSCT. STUDY DESIGN: The study included 59 patients diagnosed and treated for multiple myeloma in 1998-2004. Cells with coexpression of CD38+++CD138++CD56+ and lacking the expression of CD45, CD19, CD10, CD20, and CD23 were considered CPC in flow cytometry. RESULTS: The risk of death and progression after auto-PBSCT increased significantly by 10% (P < .021) and 8% (P < .034) per 1 × 106/kg of the CPC number, respectively. For CPC number above 2.96 × 106/kg overall survival achieved clinical significance. Two years after auto-PBSCT, the risk of death was independent of CPC number among the patients who survived (P = .70). Analogous conclusions concerned results of progression-free survival at 1 year after auto-PBSCT. CONCLUSIONS: High clonal plasma cell contamination (>2.96 ×1 06/kg; 90th percentile of CPC number) is associated with the worst progression-free survival and overall survival. Therefore purging in vitro might be considered for the patients with the highest CPC contamination. Negative consequences of CPC contamination on the risk of death are observed for only 2 years after auto-PBSCT. Thereafter only those patients who had lower CPC contamination survived.

Azacitidine for Relapse After Allogeneic Stem Cell Transplantation-Single-Center Study.

BACKGROUND: Relapse is the leading cause of treatment failure for myeloid malignancies treated with allogeneic hematopoietic stem cell transplantation. Treatment options are very limited and use of azacitidine is one of the available options. METHODS: This was a retrospective, single-institution study. Of 28 evaluated patients, 18 were males, and the median age was 60 years (range, 15-78). There were 15 patients with acute myeloid leukemia, 8 with myelodysplastic syndrome, 4 with chronic myelomonocytic leukemia, and 1 with primary myelofibrosis. Ten patients received azacitidine for overt relapse, 14 received it as a preemptive therapy, and 4 others received it as maintenance treatment after allo-hematopoietic cell transplant (HSCT). Eleven patients received a donor lymphocyte infusion (DLI). RESULTS: The patients received median 5 (1-9) cycles of azacitidine in preemptive and maintenance therapy and median 2.5 (1-9) cycles in patients with relapse. Thirty-nine percent of patients received DLIs. Median overall survival was 6.1 months (95% CI, 0.7-13) for relapse therapy vs 21.2 months (95% CI, 8.4-inf) for preemptive therapy. Among patients treated for relapse, 30% achieved temporary disease control and underwent the second allo-HSCT. A complete, cytogenetic remission was achieved in 50% of patients and stable minimal residual disease in 14% of patients in a group with preemptive therapy. Toxicity was considerable; neutropenia (71%), anemia (14%), thrombocytopenia (36%), and serious infections (36%) were observed in the preemptive setting. CONCLUSIONS: These data support the notion that azacitidine is best used as a preemptive therapy against relapse for patients after allo-HSCT performed for myeloid malignancy. Applying azacitidine as therapy for ongoing relapse after allo-HSCT may lead to stable disease and allow for better performance of the second allo-HSCT.

Rhinosinusitis in Acute Leukemia Patients Undergoing Allogeneic Stem Cell Transplantation-A Single-Center Experience.

BACKGROUND: Although rhinosinusitis constitutes a major clinical problem in general population, data on rhinosinusitis in patients undergoing allogeneic hematopoietic stem cell transplantation (alloHSCT) are scarce. Therefore, the aim of the study was to assess the frequency of rhinosinusitis, the impact of rhinosinusitis on post-alloHSCT outcome, and to analyze risk factors potentially predisposing to rhinosinusitis. METHODS: Retrospective analysis of acute leukemia patients undergoing alloHSCT. RESULTS: A total of 87 patients (49 male), with a median age of 36 years (range, 18-58), transplanted from 1999 to 2010, were enrolled; 61 patients suffered from acute myeloid leukemia (AML) and 26 of acute lymphoblastic leukemia (ALL). Fifteen patients (17.2%) experienced rhinosinusitis before transplantation, among whom 5 (33%) experienced rhinosinusitis after alloHSCT; 22 patients (25.3%), 12 AML and 10 ALL, experienced rhinosinusitis after alloHSCT. The median time to rhinosinusitis was 200 days (range, 1-2,044). 11 patients experienced rhinosinusitis during the 1st 100 days after transplantation, 8 during the 1st 30 days. Post-alloHSCT rhinosinusitis did not affect overall survival of transplant patients (P = .35). In univariate analysis only total body irradiation as part of conditioning (odds ratio [OR], 2.78; 95% CI, 1-7.77) and previous nasal packing (OR, 5.18; 95% CI, 1.22-23.43) were associated with higher incidence of rhinosinusitis. In multivariate analysis, none of the analyzed parameters was shown to have an impact on rhinosinusitis development. CONCLUSIONS: Rhinosinusitis is a frequent medical condition in patients undergoing alloHSCT. The overall survival of patients developing rhinosinusitis after HSCT is similar to survival of patients who do not. No risk factors for developing rhinosinusitis could be identified.

Azacitidine Use After Allogeneic Stem Cell Transplantation-Results From the Polish Adult Leukemia Group.

BACKGROUND: Relapse of primary hematologic disease constitutes an important reason for failure of allogeneic hematopoietic stem cell transplantation (alloHSCT). There are very few treatment modalities for this indications. Therefore, there is a need for novel effective therapies and even more for the prevention of relapse. There are scarce data that azacitidine can be used for these purposes. METHODS: At the Polish Adult Leukemia Group, we retrospectively analyzed the results of azacitidine treatment after alloHSCT. Relapsing patients, patients with minimal residual disease/mixed chimerism, and patients in complete remission with high risk of relapse were analyzed separately. There were 17 patients, 6 with myelodysplastic syndrome, 11 with acute myeloid leukemia, 8 male, and overall median age of 56 years (range, 15-78); 7 patients received donor lymphocyte infusion (DLI). RESULTS: Patients treated because of relapse received a median of 3 (range, 1-6) cycles of azacitidine, patients receiving preemptive treatment received a median of 4 cycles (range, 2-6), and those on maintenance received a median of 5 cycles (range, 3-5). Toxicity was considerable, especially in relapse-neutropenia (67%), anemia (67%), thrombocytopenia (100%), serious infections (78%)-and preemptive settings. Median overall survival of patients treated for relapse reached 6.8 months (95% confidence interval [CI], 0.7-∞), with better survival observed in patients with temporary disease control (7.7 vs 4.7 mo) and without previous exposure to azacitidine (7.7 vs 3.4 mo). One-year overall survival reached 75% (95% CI, 13%-96%) for preemptive and 50% (95% CI, 0%-91%) for maintenance treatment. DLI did not aggravate graft-versus-host disease. CONCLUSIONS: Effectiveness of azacitidine in relapsing patients is disappointing. Azacitidine seems to be promising in preemptive and maintenance settings. Toxicity is considerable. Further research is needed.

Update on the incidence of metamizole sodium-induced blood dyscrasias in Poland.

Metamizole sodium (metamizole) is a popular non-opioid analgesic and a common non-prescription product in Poland. Controversy exists regarding the level of risk of agranulocytosis or aplastic anaemia associated with its use. Two previous pharmacovigilance studies conducted in Poland found the risk was low. Twenty-four of the 25 haematology centres that provide specialist care for the 30 million adults in Poland participated in this prospective 12-month study. Twenty-one cases of agranulocytosis, 48 of aplastic anaemia, 15 of neutropenia and 11 of pancytopenia were reported. Of these cases, three (two agranulocytosis; one aplastic anaemia) were judged as being possibly related to metamizole. Crude estimates of the rate of agranulocytosis and aplastic anaemia associated with metamizole were 0.16 and 0.08 cases/million person-days of use, respectively. Ongoing national safety surveillance in Poland shows that, despite the possibility of drug-induced blood dyscrasias with metamizole, the risk is very low.