Long-term outcome of peripheral T-cell lymphomas: Ten-year follow-up of the International Prospective T-cell Project.

Peripheral T-cell lymphomas (PTCLs) are a heterogeneous group of haematological cancers with generally poor clinical outcomes. However, a subset of patients experience durable disease control, and little is known regarding long-term outcomes. The International T-cell Lymphoma Project (ITCLP) is the largest prospectively collected cohort of patients with PTCLs, providing insight into clinical outcomes at academic medical centres globally. We performed a long-term outcome analysis on patients from the ITCLP with available 10-year follow-up data (n = 735). The overall response rate to first-line therapy was 68%, while 5- and 10-year overall survival estimates were 49% and 40% respectively. Most deaths occurred prior to 5 years, and for patients alive at 5 years, the chance of surviving to 10 years was 84%. However, lymphoma remained the leading cause of death in the 5- to 10-year period (67%). Low-risk International Prognostic Index and Prognostic Index for T-cell lymphoma scores both identified patients with improved survival, while in multivariate analysis, age >60 years and Eastern Cooperative Oncology Group performance status 2-4 were associated with inferior outcomes. The favourable survival seen in patients achieving durable initial disease control emphasizes the unmet need for optimal front-line therapeutic approaches in PTCLs.

Clinical and histopathology characteristics of Castleman disease: a multicenter study of 51 Brazilian patients.

Castleman's disease (CD) is a rare and heterogeneous lymphoproliferative disorder, with limited available clinical information in Brazil. A retrospective study was carried out through information contained in the medical records of 51 patients, between July 1999 and June 2020. Seven patients were excluded, and 44 were analyzed in total. The average age of unicentric CD (UCD) patients was 35 years old and of multicentric CD (MCD) patients was 49 years old (p = 0.013). Regarding gender, there was a predominance of females among patients with UCD (68.4%) and males in patients with MCD (57.9%) (p = 0.103). The most common site of involvement in UCD was the cervical region (36.8%). A total of 73.7% of patients with UCD and 68.4% of patients with MCD presented the histological form hialyne-vascular (HV) (p = 0.499). Most patients with laboratory abnormalities had MCD. A total of 78% of the patients were asymptomatic, with the majority of symptomatic patients with MCD (p = 0.042). Only two of the 27 patients evaluated for the presence of human immunodeficiency virus (HIV) had positive serology. HHV-8 was evaluated in 14 cases, being positive in two. Of the patients with UCD, 94.7% underwent excisional biopsy, against only 41.2% of patients with MCD (p = 0.01). The mean follow-up was 61 months. We observed similarities in the clinical profile between patients in our study and patients described in the literature, such as gender, mean age, B symptoms, visceromegaly, fluid accumulation, and treatment. Unlike the literature, the cervical region was the most affected site, besides the greater association of the HV histological subtype among patients with MCD.

Treatment patterns and outcomes for Hodgkin Lymphoma patients aged 60 and older: a report from the Brazilian Prospective Hodgkin Lymphoma Registry.

The treatment of older patients with Hodgkin lymphoma (HL) remains a challenge. We sought to identify the treatment patterns and outcomes in older HL patients included in the Brazilian HL registry (NCT02589548). A total of 136 patients with HIV-negative classic HL, aged ≥ 60 years, diagnosed between 2009 and 2018, were analyzed. The median age was 66 years old (60-90), 72% had advanced disease, 62% had a high IPS, and 49% had a nodular sclerosis subtype. Median follow-up was 64 months for alive patients. ABVD was the front-line treatment in 96% of patients. Twenty-one patients (15%) died during front-line treatment. The 5-year PFS and 5-year OS rates were 55% and 59%, respectively. The 5-year OS rates in localized and advanced disease were 81% and 51% (p=0.013). Lung toxicity developed in 11% of the patients treated with ABVD. Bleomycin was administered for > 2 cycles in 65% of patients. Compared with 2009-2014, there was a decrease in the use of bleomycin for > 2 cycles in 2015-2018 (88% × 45%, p<0.0001). The impact of socioeconomic status (SES) on outcomes was studied in patients treated with ABVD. After adjusting for potential confounders, lower SES remained independently associated with poorer survival (HR 2.22 [1.14-4.31] for OS and HR 2.84 [1.48-5.45] for PFS). Treatment outcomes were inferior to those observed in developed countries. These inferior outcomes were due to an excess of deaths during front-line treatment and the excessive use of bleomycin. SES was an independent factor for shorter survival.

Characteristics and clinical outcomes of patients with ALK-positive anaplastic large cell lymphoma: Report from the prospective international T-cell lymphoma project.

The T-cell Lymphoma Project is an international registry prospective study that enrolled patients with newly diagnosed peripheral T-cell and NK-cell lymphomas (PTCL). The main objective was to define the clinical features and outcomes, establishing a robust benchmark for future clinical trials. Seventy-four institutions from 14 countries in North America, South America, Europe, and Asia collected data on patients diagnosed and treated at their respective centers between September 2006 and February 2018. Among 1553 PTCL patients, 131 (8.4% of the total cohort) were confirmed to have anaplastic large cell lymphoma - kinase positive (ALCL, ALK+). The median age of the patients was 39 years (18-84). Sixty-five patients (66%) had advanced-stage disease, although majority (45 patients, 54%) had a low-risk International Prognostic Index (IPI) score (0-1). Of 97 patients treated with chemotherapy, 97% received anthracycline-containing regimens. The overall response rate was 81%, with 69 patients (70%) achieving complete remission. Estimated OS and PFS at 3 years were 77% (95% CI: 54%-99%) and 68% (95% CI: 46%-90%), respectively, and at 5 years were very similar, 77% of OS (95% CI: 62%-92%) and 64% of PFS (95% CI: 34%-94%). Multivariate analysis for PFS showed advanced stage (hazard ratios [HR]: 4.72, 95% CI: 1.43-23.9, p = 0.015), elevated lactate dehidrogenade (LDH) (HR 4.85; 95% CI: 1.73-13.60, p = 0.001), and Eastern Cooperative Oncology Group Performance Status scale (ECOG-PS) ≥2 (HR: 5.25; 95% CI: 1.68-16.4, p = 0.024). For OS, elevated LDH (HR: 3.77; 95% CI: 1.98-14.17, p = 0.014) and ECOG-PS ≥2 (HR: 4.59; 95% CI: 1.46-14.39, p = 0.004) were identified. In summary, although the outcome of ALK+ ALCL is superior to that of other PTCLs, it remains sufficiently favorable, given the young median age of the patients. Our results confirm the usefulness of both IPI and Prognostic Index for T-cell Lymphoma (PIT) in identifying groups of patients with different outcomes. Clinical Trials ID: NCT01142674.

Incidence and outcomes of rare T cell lymphomas from the T Cell Project: hepatosplenic, enteropathy associated and peripheral gamma delta T cell lymphomas.

The T Cell Project was the largest prospective trial to explore the incidence, treatment patterns, and outcomes for T cell lymphomas. The rare subtypes of T cell lymphomas, including hepatosplenic T cell lymphoma (HSTCL), enteropathy associated T cell lymphoma (EATL), and peripheral gamma delta T cell lymphomas (PGDTCLs) are poorly represented in most studies and there is little data regarding treatment patterns. We report results from 115 patients with hepatosplenic (n = 31), enteropathy associated (n = 65), and PGDTCLs (n = 19). While anthracycline regimens were most commonly used as first line therapy, response rates ranged from 20%-40% and were suboptimal for all groups. Autologous stem cell transplantation was performed as a consolidation in first remission in a small number of patients (33% of HSTCL, 7% of EATL, and 12% of PGDTCL), and four patients with HSTCL underwent allogeneic stem cell transplantation in first remission. The progression free survival at 3 years ranged from 28%-40% for these rare subtypes, and the overall survival at 3 years was most favorable for PGDTCL (70%). These data highlight the need for novel treatment approaches for rare subtypes of T cell lymphomas and for their inclusion in clinical trials.

Lower socioeconomic status is independently associated with shorter survival in Hodgkin Lymphoma patients-An analysis from the Brazilian Hodgkin Lymphoma Registry.

Socioeconomic status (SES) is a well-known determinant of outcomes in cancer. The purpose of this study was to analyze the impact of the SES on the outcomes of Hodgkin lymphoma (HL) patients from the Brazilian Prospective HL Registry. SES stratification was done using an individual asset/education-based household index. A total of 624 classical HL patients with diagnosis from January/2009 to December/2014, and treated with ABVD (doxorubicin, bleomycin, vinblastine and dacarbazine), were analyzed. The median follow-up was 35.6 months, and 33% were classified as lower SES. The 3-year progression- free survival (PFS) in higher and lower SES were 78 and 64% (p < 0.0001), respectively. The 3-year overall survival (OS) in higher and lower SES were 94 and 82% (p < 0.0001), respectively. Lower SES patients were more likely to be ≥ 60 years (16 vs. 8%, p = 0.003), and to present higher risk International Prognostic score (IPS) (44 vs. 31%, p = 0.004) and advanced disease (71 vs. 58%, p = 0.003). After adjustments for potential confounders, lower SES remained independently associated with poorer survival (HR = 3.12 [1.86-5.22] for OS and HR = 1.66 [1.19-2.32] for PFS). The fatality ratio during treatment was 7.5 and 1.3% for lower and higher SES (p = 0.0001). Infections and treatment toxicity accounted for 81% of these deaths. SES is an independent factor associated with shorter survival in HL in Brazil. Potential underlying mechanisms associated with the impact of SES are delayed diagnosis and poorer education. Educational and socio-economic support interventions must be tested in this vulnerable population.

The outcome of peripheral T-cell lymphoma patients failing first-line therapy: a report from the prospective, International T-Cell Project.

This analysis explored factors influencing survival of patients with primary refractory and relapsed peripheral T-cell lymphomas enrolled in the prospective International T-cell Project. We analyzed data from 1020 patients with newly diagnosed disease, enrolled between September 2006 and December 2015. Out of 937 patients who received first-line treatment, 436 (47%) were identified as refractory and 197 (21%) as relapsed. Median time from the end of treatment to relapse was 8 months (range 2-73). Overall, 75 patients (8%) were consolidated with bone marrow transplantation, including 12 refractory and 22 relapsed patients. After a median follow up of 38 months (range 1-96 months) from documentation of refractory/relapsed disease, 440 patients had died. The median overall survival (OS) was 5.8 months; 3-year overall survival rates were 21% and 28% for refractory and relapsed patients, respectively (P<0.001). Patients receiving or not salvage bone marrow transplantation had a 3-year survival of 48% and 18%, respectively (P<0.001). In a univariate Cox regression analysis, refractory disease was associated with a higher risk of death (HR=1.43, P=0.001), whereas late relapse (>12 months, HR 0.57, P=0.001) and salvage therapy with transplantation (HR=0.36, P<0.001) were associated with a better OS. No difference was found in OS with respect to histology. This study accurately reflects outcomes for patients treated according to standards of care worldwide. Results confirm that peripheral T-cell lymphomas patients had dismal outcome after relapse or progression. Patients with chemotherapy sensitive disease who relapsed after more than 12 months might benefit from consolidation bone marrow transplantation.

Treatment outcomes for Hodgkin lymphoma: First report from the Brazilian Prospective Registry.

Data about Hodgkin lymphoma (HL) in developing countries are scarce and suggest the existence of substantial disparities in healthcare and outcomes in large areas of the world. In 2009, a prospective registry of HL was implemented in Brazil. Web-based data were contributed by 20 institutions across the country participating in the Brazilian Prospective Hodgkin's Lymphoma Registry. The aim of this study was to present the clinical features and outcomes of newly diagnosed patients with HL aged 13 to 90 years. Multivariate Cox regression models were used to estimate progression-free (PFS) and overall survival (OS) by clinical factors. A total of 674 patients with classical HL were analysed, with a median follow-up of 37 months. Median age was 30 years (13-90). The median time from the onset of symptoms to diagnosis was 6 months (0-60). Only 6% of patients had early favourable disease, while 65% had advanced disease. Stage IVB was present in 26% and a high-risk International Prognostic Score in 38%. Doxorubicin, bleomycin, vinblastine, and dacarbazine was used in 93%. The median dose of radiotherapy was 36 Gy for localized disease and 32 Gy for advanced disease. The 3 year PFS in early favourable, early unfavourable, and advanced disease were 95%, 88%, and 66%, respectively. High-risk International Prognostic Score, advanced disease, and age greater than or equal to 60 were independently associated with poorer PFS and OS; performance status greater than or equal to 2 was also associated with a poorer OS. Poor-risk patients predominated. Radiation doses for localized disease appear higher than current recommendations. Outcomes appear inferior in developing countries than in developed countries. Delayed diagnosis is probably a major factor underlying these findings. Scattered reports from developing nations suggest that many aspects of standard care in developed countries remain unmet needs for populations living in developing countries. The present report contributes to this body of data, with a proper description of what is currently achieved in urban areas in Brazil.

Transformed follicular lymphoma.

Follicular Lymphoma (FL) is the second most common type of non-Hodgkin lymphoma and is considered to be the prototype of indolent lymphomas. Histologic transformation into an aggressive lymphoma, which is expected to occur at a rate of 2 to 3% each year, is associated with rapid progression, treatment resistance, and poor prognosis. Recent modifications to the physiopathologic mechanism of transformed follicular lymphoma (t-FL) have been proposed, including genetic and epigenetic mechanisms as well as a role for the microenvironment. Although t-FL is considered a devastating complication, as it is associated with treatment-refractory disease and a dismal outcome, recent data in the rituximab era have suggested that not only is the prognosis less severe than reported in the previous literature but the risk of transformation is also lower. Thus, this study aimed to review the most recent research on t-FL in an attempt to better understand the clinical meaning of transformation from FL to diffuse large B cell lymphoma (DLBCL) and the impact of current treatment strategies on the curability of this intriguing subentity of lymphoma.

The impact of preapheresis white blood cell count on autologous peripheral blood stem cell collection efficiency and HSC infusion side effect rate.

BACKGROUND: Autologous peripheral blood hematopoietic stem cell (PBSC) collection efficiency (CE) is reportedly affected by the patient's blood properties; however, studies to identify factors correlated with CE have shown inconsistent results. Additionally, variables such as stem cell graft granulocyte content and patient age, sex, and underlying disease, may be associated with hematopietic stem cell (HSC) infusion-related adverse reactions. In this study, we evaluated the correlation of preleukapheresis PB granulocyte count and PBSC harvest variables with CD34+ collection yield and efficiency, and thawed HSC infusion side effect occurrence. PATIENTS AND METHODS: We evaluated data from 361 patients who had undergone autologous PBSC transplant. Large volume leukapheresis was the method for PBSC collection. Complete Blood Count and CD34+ cell enumeration were performed in the preapheresis PB and the apheresis product sample. The PBSC grafts were submitted to non-controlled rate freezing after addition of 5% DMSO plus 6% hidroxyethylstarch as a cryoprotectant solution. The cryopreserved graft was thawed in a 37°C water bath and then infused without further manipulation. RESULTS: The CD34+ yield was associated with preapheresis PB CD34+ count and immature granulocyte count. The PBSC CE was negatively correlated with preapheresis white blood cell (WBC), immature granulocyte and granulocyte count. The leukapheresis product total nucleated cell (TNC) and granulocyte content was correlated with the thawed graft infusion side effect occurrence. CONCLUSION: This study has shown that preapheresis PB WBC and granulocyte counts were associated with leukapheresis CE. Additionally, the leukapheresis product TNC and granulocyte content was correlated with thawed graft infusion side effect occurrence.

High ΔNp73/TAp73 ratio is associated with poor prognosis in acute promyelocytic leukemia.

The TP73 gene transcript is alternatively spliced and translated into the transcriptionally active (TAp73) or inactive (ΔNp73) isoforms, with opposite effects on the expression of p53 target genes and on apoptosis induction. The imbalance between ΔNp73 and TAp73 may contribute to tumorigenesis and resistance to chemotherapy in human cancers, including hematologic malignancies. In acute promyelocytic leukemia (APL), both isoforms are expressed, but their relevance in determining response to therapy and contribution to leukemogenesis remains unknown. Here, we provide the first evidence that a higher ΔNp73/TAp73 RNA expression ratio is associated with lower survival, lower disease-free survival, and higher risk of relapse in patients with APL homogeneously treated with all-trans retinoic acid and anthracycline-based chemotherapy, according to the International Consortium on Acute Promyelocytic Leukemia (IC-APL) study. Cox proportional hazards modeling showed that a high ΔNp73/TAp73 ratio was independently associated with shorter overall survival (hazard ratio, 4.47; 95% confidence interval, 1.64-12.2; P = .0035). Our data support the hypothesis that the ΔNp73/TAp73 ratio is an important determinant of clinical response in APL and may offer a therapeutic target for enhancing chemosensitivity in blast cells.

Improving acute promyelocytic leukemia (APL) outcome in developing countries through networking, results of the International Consortium on APL.

Thanks to modern treatment with all-trans retinoic acid and chemotherapy, acute promyelocytic leukemia (APL) is now the most curable type of leukemia. However, this progress has not yielded equivalent benefit in developing countries. The International Consortium on Acute Promyelocytic Leukemia (IC-APL) was established to create a network of institutions in developing countries that would exchange experience and data and receive support from well-established US and European cooperative groups. The IC-APL formulated expeditious diagnostic, treatment, and supportive guidelines that were adapted to local circumstances. APL was chosen as a model disease because of the potential impact on improved diagnosis and treatment. The project included 4 national coordinators and reference laboratories, common clinical record forms, 5 subcommittees, and laboratory and data management training programs. In addition, participating institutions held regular virtual and face-to-face meetings. Complete hematological remission was achieved in 153/180 (85%) patients and 27 (15%) died during induction. After a median follow-up of 28 months, the 2-year cumulative incidence of relapse, overall survival (OS), and disease-free survival (DFS) were 4.5%, 80%, and 91%, respectively. The establishment of the IC-APL network resulted in a decrease of almost 50% in early mortality and an improvement in OS of almost 30% compared with historical controls, resulting in OS and DFS similar to those reported in developed countries.

BCR-ABL Mutations in Chronic Myeloid Leukemia Treated With Tyrosine Kinase Inhibitors and Impact on Survival.

This is the largest Latin American study of BCR-ABL mutations in chronic myeloid leukemia (CML) patients, resistant to imatinib (IM). In 195/467 (41%) patients, mutations were detected. The most frequent mutation was T315I (n = 31, 16%). Progression-free (PFS) and overall survival (OS) at 5 years were lower in patients with BCR-ABL mutations (43% vs. 65%, p = 0.07 and 47% vs. 72%, p = 0.03, respectively) and in those with the T315I mutation (p = 0.003 and p = 0.03). OS and PFS were superior in subgroup who switched to second generation inhibitors (SGIs) after IM failure (OS: 50% vs. 39% p = 0.01; PFS: 48% vs. 30% p = 0.02). BCR-ABL mutations conferred a significant poor prognosis in CML patients.

BCR-ABL mutations in chronic myeloid leukemia treated with tyrosine kinase inhibitors and impact on survival.

This is the largest Latin American study of BCR-ABL mutations in chronic myeloid leukemia (CML) patients, resistant to imatinib (IM). In 195/467 (41%) patients, mutations were detected. The most frequent mutation was T315I (n = 31, 16%). Progression-free (PFS) and overall survival (OS) at 5 years were lower in patients with BCR-ABL mutations (43% vs. 65%, p = 0.07 and 47% vs. 72%, p = 0.03, respectively) and in those with the T315I mutation (p = 0.003 and p = 0.03). OS and PFS were superior in subgroup who switched to second generation inhibitors (SGIs) after IM failure (OS: 50% vs. 39% p = 0.01; PFS: 48% vs. 30% p = 0.02). BCR-ABL mutations conferred a significant poor prognosis in CML patients.

Deferasirox in patients with iron overload secondary to hereditary hemochromatosis: results of a 1-yr Phase 2 study.

This open-label, prospective, phase 2 study evaluated the safety and efficacy of deferasirox (10 ± 5 mg/kg/d) in patients with hereditary hemochromatosis (HH) and iron overload refractory to or intolerant of phlebotomy. Ten patients were enrolled and all completed the 12-month treatment period. There were significant decreases from baseline to end of study (i.e., 12 months) in median serum ferritin (P < 0.001), mean transferrin saturation (P < 0.05), median liver iron concentration (P < 0.001), and mean alanine aminotransferase (P < 0.05). The median time to achieve serum ferritin reduction ≥50% compared to baseline was 7.53 months. The most common adverse events were mild, transient diarrhea (n = 5) and nausea (n = 2). No patient experienced an increase in serum creatinine that exceeded the upper limit of normal. These data confirm that deferasirox was well tolerated and effective in reducing iron burden in patients with hereditary hemochromatosis and could be a safe alternative to phlebotomy in selected patients.

Rho kinase inhibition drives megakaryocyte polyploidization and proplatelet formation through MYC and NFE2 downregulation.

The processes of megakaryocyte polyploidization and demarcation membrane system (DMS) formation are crucial for platelet production, but the mechanisms controlling these processes are not fully determined. Inhibition of Rho kinase (ROCK) signalling leads to increased polyploidization in umbilical cord blood-derived megakaryocytes. To extend these findings we determined the effect of ROCK inhibition on development of the DMS and on proplatelet formation. The underlying mechanisms were explored by analysing the effect of ROCK inhibition on the expression of MYC and NFE2, which encode two transcription factors critical for megakaryocyte development. ROCK inhibition promoted DMS formation, and increased proplatelet formation and platelet release. Rho kinase inhibition also downregulated MYC and NFE2 expression in mature megakaryocytes, and this down-regulation correlated with increased proplatelet formation. Our findings suggest a model whereby ROCK inhibition drives polyploidization, DMS growth and proplatelet formation late in megakaryocyte maturation through downregulation of MYC and NFE2 expression.

Prognostic impact of KMT2E transcript levels on outcome of patients with acute promyelocytic leukaemia treated with all-trans retinoic acid and anthracycline-based chemotherapy: an International Consortium on Acute Promyelocytic Leukaemia study.

The KMT2E (MLL5) gene encodes a histone methyltransferase implicated in the positive control of genes related to haematopoiesis. Its close relationship with retinoic acid-induced granulopoiesis suggests that the deregulated expression of KMT2E might lead acute promyelocytic leukaemia (APL) blasts to become less susceptible to the conventional treatment protocols. Here, we assessed the impact of KMT2E expression on the prognosis of 121 APL patients treated with ATRA and anthracycline-based chemotherapy. Univariate analysis showed that complete remission (P = 0·006), 2-year overall survival (OS) (P = 0·005) and 2-year disease-free survival (DFS) rates (P = 0·037) were significantly lower in patients with low KMT2E expression; additionally, the 2-year cumulative incidence of relapse was higher in patients with low KMT2E expression (P = 0·04). Multivariate analysis revealed that low KMT2E expression was independently associated with lower remission rate (odds ratio [OR]: 7·18, 95% confidence interval [CI]: 1·71-30·1; P = 0·007) and shorter OS (hazard ratio [HR]: 0·27, 95% CI: 0·08-0·87; P = 0·029). Evaluated as a continuous variable, KMT2E expression retained association with poor remission rate (OR: 10·3, 95% CI: 2·49-43·2; P = 0·001) and shorter survival (HR: 0·17, 95% IC: 0·05-0·53; P = 0·002), while the association with DFS was of marginal significance (HR: 1·01; 95% CI: 0·99-1·02; P = 0·06). In summary, low KMT2E expression may predict poor outcome in APL patients.

Peripheral blood stem cell yield calculated using preapheresis absolute CD34+ cell count, peripheral blood volume processed, and donor body weight accurately predicts actual yield at multiple centers.

BACKGROUND: Accurate prediction of stem cell yield is important for planning leukapheresis procedures. A formula has been published (Pierelli et al., Vox Sang 2006;91:126-34) to estimate the CD34+ dose collected on the first day of leukapheresis that was based on the preapheresis peripheral blood (PB) CD34+ counts, the blood volume processed, and the donor's weight. The aim of this study was to assess the predictive value of this formula. STUDY DESIGN AND METHODS: Data were retrospectively collected on 1126 consecutive PB stem cell harvests conducted at five institutions. Information on age, sex, diagnosis, weight, preapheresis absolute peripheral CD34+ count, total blood volume processed, and CD34+ cells harvested per kilogram of body weight on the first day of apheresis was collected. RESULTS: Among donors at least 18 years old, Pearson's correlation coefficient (r) between actual yield (AY) and predicted yield (PY) was 0.76. To characterize this correlation, AY and PY were classified as being within the conventionally acceptable CD34+ doses (>2 × 10(6) -5 × 10(6) cells/kg), below this range (≤2 × 10(6) cells/kg), or above it (>5 × 10(6) cells/kg). The positive predictive value (PPV) of PY was estimated considering the distribution of AY as the "gold standard." PPV was relatively high for PY of more than 5 × 10(6) cells/kg (85%), moderate for PY of not more than 2 × 10(6) cells/kg (72%), and low for PY more than 2 × 10(6) to 5 × 10(6) cells/kg (56%). A consistent pattern was observed within institutions. CONCLUSION: The formula of Pierelli et al. is associated with a PPV that is high, moderate, and relatively low for the corresponding predicted CD34+ doses.

Internal tandem duplication of the FLT3 gene confers poor overall survival in patients with acute promyelocytic leukemia treated with all-trans retinoic acid and anthracycline-based chemotherapy: an International Consortium on Acute Promyelocytic Leukemia study.

Activating internal tandem duplication (ITD) mutations in the fms-like tyrosine kinase 3 (FLT3) gene (FLT3-ITD) are associated with poor outcome in acute myeloid leukemia, but their prognostic impact in acute promyelocytic leukemia (APL) remains controversial. Here, we screened for FLT3-ITD mutations in 171 APL patients, treated with all-trans retinoic acid (ATRA) and anthracycline-based chemotherapy. We identified FLT3-ITD mutations in 35 patients (20 %). FLT3-ITD mutations were associated with higher white blood cell counts (P < 0.0001), relapse-risk score (P = 0.0007), higher hemoglobin levels (P = 0.0004), higher frequency of the microgranular morphology (M3v) subtype (P = 0.03), and the short PML/RARA (BCR3) isoform (P < 0.0001). After a median follow-up of 38 months, FLT3-ITD(positive) patients had a lower 3-year overall survival rate (62 %) compared with FLT3-ITD(negative) patients (82 %) (P = 0.006). The prognostic impact of FLT3-ITD on survival was retained in multivariable analysis (hazard ratio: 2.39, 95 % confidence interval [CI] 1.17-4.89; P = 0.017). Nevertheless, complete remission (P = 0.07), disease-free survival (P = 0.24), and the cumulative incidence of relapse (P = 0.94) rates were not significantly different between groups. We can conclude that FLT3-ITD mutations are associated with several hematologic features in APL, in particular with high white blood cell counts. In addition, FLT3-ITD may independently predict a shorter survival in patients with APL treated with ATRA and anthracycline-based chemotherapy.