Background
Patients with cancer are considered highly vulnerable to the recent coronavirus disease 2019 (COVID‐19) pandemic. However, there are still few data on COVID‐19 occurring in hematologic ...patients.
Methods
One hundred two patients with COVID‐19 symptoms and a nasopharyngeal swab positive for severe acute respiratory syndrome coronavirus 2 seen at 2 hematologic departments located in Lombardy, Italy, during March 2020 were studied. Risk factors for acquiring COVID‐19 were analyzed by comparisons of patients with COVID‐19 and the standard hematologic population managed at the same institutions in 2019. Thirty‐day survival was compared with the survival of matched uninfected control patients with similar hematologic disorders and nonhematologic patients affected by COVID‐19.
Results
Male sex was significantly more prevalent in patients with COVID‐19. The infection occurred across all different types of hematologic disease; however, the risk of acquiring a COVID‐19 infection was lower for patients with chronic myeloproliferative neoplasms, including chronic myeloid leukemia, and higher for patients with immune‐mediated anemia on immunosuppressive‐related treatments. The 30‐day mortality rate was 39.2%, which was higher than the rates for nonhematologic patients with COVID‐19 (23.5%; P = .02) and uninfected hematologic controls (3%; P < .001). The severity of the respiratory syndrome at presentation and active hematologic treatment were independently associated with a worse prognosis. Neither diagnosis nor disease status affected the prognosis. The worst prognosis was demonstrated among patients on active hematologic treatment and those with more severe respiratory syndrome at COVID‐19 presentation.
Conclusions
During the COVID‐19 pandemic, patients should be advised to seek medical attention at the earliest signs of dyspnea and/or respiratory infection. Physicians should perform a risk‐benefit analysis to determine the impact of temporarily deferring nonlifesaving treatments versus the risk of adverse outcomes associated with COVID‐19.
Lay Summary
Coronavirus disease 2019 (COVID‐19) infection occurs across all different types of hematologic disease; however, the risk of acquiring it is lower for patients with chronic myeloproliferative neoplasms, including chronic myeloid leukemia, and higher for patients with immune‐mediated anemia on immunosuppressive treatment.
The 30‐day mortality rate is 39.2%, which is far higher than the rates for both uninfected hematologic controls (3%; P < .001) and nonhematologic patients with COVID‐19 (23.5%; P = .02) despite matching for age, sex, comorbidities, and severity of disease.
Variables independently associated with a worse prognosis are the severity of the respiratory syndrome at presentation and any type of active hematologic treatment. Neither diagnosis nor disease status influence the prognosis.
Hematologic patients affected by coronavirus disease 2019 (COVID‐19) have a severe prognosis and a 30‐day mortality rate of 39.2%. The need for oxygen and ongoing hematologic treatment at the presentation of COVID‐19 are the main risk factors associated with a worse outcome.
Abstract
We performed a multicenter study to validate the concept that a simple comprehensive geriatric assessment (CGA) can identify elderly, non-fit patients with diffuse large B-cell lymphoma ...(DLBCL) in whom curative treatment is not better then palliation, and to analyze potential benefits of treatment modulation after further subdividing the non-fit category by CGA criteria. One hundred and seventy-three patients aged > 69 treated with curative or palliative intent by clinical judgement only were grouped according to CGA into fit (46%), unfit (16%) and frail (38%) categories. Two-year overall survival (OS) was significantly better in fit than in non-fit patients (84% vs. 47%; p < 0.0001). Survival in unfit and frail patients was not significantly different. Curative treatment slightly improved 2-year OS in unfit (75% vs. 45%) but not in frail patients (44% vs. 39%). CGA was confirmed as very efficient in identifying elderly patients with DLBCL who can benefit from a curative approach. Further efforts are needed to better tailor therapies in non-fit patients.
We evaluated the impact of invasive pulmonary aspergillosis (IPA) on epidemiology and outcome in acute leukemia (AL), analyzing all acute myeloid (AML) and acute lymphoblastic leukemia (ALL) ...consecutively admitted to our Institution during a 5-year period of observation. Only AML patients received anti-mold prophylaxis. Among 175 AL patients (136 AML/39 ALL), possible and proven/probable IPA were diagnosed in 28 (16%). Frequency of IPA was similar in AML (16.2%) and in ALL (15.4%). Two-year overall survival (OS) was significantly affected by IPA (no IPA: 69.8% vs IPA: 31.7% p = .002). OS was similar in patients with proven/probable (28.2%) and possible IPA (36.4%) (p = .003 and .065, respectively). When censoring patients at transplant, IPA still affected 2-year survival (49.6% vs 79.2%, p = .02), but only proven/probable IPA was associated with lower survival (34.7%, p = .0003). IPA negatively impacts on long-term survival of leukemia patients; antifungal prophylaxis should be adopted also during induction in ALL and in AML beyond induction therapy.
Consolidation treatment in acute myeloid leukemia (AML) patients achieving complete remission (CR) is warranted. High-dose cytarabine (HDAC) is considered first choice in favorable risk and an option ...in intermediate-risk AML. However, its optimal dose and schedule, as well as the benefit of additional chemotherapy agents remain controversial. Herein, we report on the long-term outcome of consecutive unselected AML patients treated with repeated courses of HDAC, with the addition of idarubicin, followed by autologous peripheral blood stem cell (PBSC) support, in order to limit toxicity, according to Northern Italy Leukemia Group (NILG) AML-01/00 study (EUDRACT number 00400673). Among 338 patients consecutively diagnosed from 2001 to 2017 at our center, 148 with high-risk AML (adverse cytogenetic, isolated FLT3-internal tandem duplication mutation, refractory to first induction) were addressed to allogeneic stem cell transplant. All other cases, 186 patients (55%), median age 53 (range 19-75), were considered standard-risk and received the NILG AML-01/00 program. After achieving CR, patients were mobilized with cytarabine 8 g/sqm to collect autologous CD34+-PBSC and received three consolidation cycles with HDAC (20 g/sqm) plus idarubicin (20 mg/sqm) per cycle, followed by reinfusion of limited doses of CD34+ PBSC (1-2x106/kg). The program was completed by 160 (86%) patients. Toxicity was acceptable. Neutrophils recovered a median of 10 days. Treatment-related mortality was 3/160 (1.8%). After a median follow-up of 66.4 months, overall survival (OS) and relapse-free survival (RFS) at 5-years were 61.4% and 52.4%, respectively. Twenty-eight selected patients aged >65 had similar outcomes. According to European leukemia net-2010 classification, the OS and RFS at 5-years were 76.4% and 65% in favorable risk, without differences between molecular subgroups, 52.3% and 47.2% in Intermediate-I, 45.2% and 36.5% in Intermediate-II risk patients, respectively. In conclusion, consolidation including repeated courses of high dose cytarabine and idarubicin, with limited PBSC support, proved feasible and very effective in nonhigh risk patients. The incorporation of novel agents in its backbone may be tested to further improve patient's prognosis.
Background: MYC rearrangements occur approximately in 5-15% of diffuse large B-cell lymphoma (DLBCL), and are known to unfavorably impact on patients (pts) survival, especially if associated to BCL2 ...or/and BCL6 rearrangements (double/triple-hit). Previous studies have shown that also a MYC gene ICN may confer a worse prognosis to these pts (Yoon, Histopathology 2008), but only few groups have transferred this observation into the clinical practice. However, this finding may account for those cases that, despite the absence of MYC rearrangements, show a similar aggressive clinical course. For this reason, a careful study of all aberrations involving MYC geneshould be widely applied. We report a single center experience on the clinical outcome of pts with MYC ICN in the setting of aggressive B-cell lymphoma.
Methods: In the study period (Aug 2011-Aug 2015) we performed FISH analysis in all consecutive pts with de novo or transformed DLBCL or B-cell lymphoma, unclassifiable (BCLU) that displayed Ki67 >80% or intense bcl2 protein expression. Interphase FISH has been performed on 23 μm thick sections of formalin fixed paraffin embedded tissues, using splitsignal DNA probes (Dako) specific for the following loci: 8q24 (MYC), 18q21 (BCL2) and 3q27 (BCL6). For each sample, 60 evaluable nuclei with complete FISH signals were scored. ICN was considered when 3 or more copies of the gene studied were identified.
Almost all pts with a MYC translocation have been treated according to Burkitt lymphoma (BL)-like regimens as first line therapy (FLT); pts with MYC ICN have been treated with BL-like regimens from 2013, whereas standard ICT (R-CHOP or R-CHOPlike) has been used for these pts diagnosed before 2013. Overall survival (OS) was evaluated by Kaplan Meier method.
Results: In the 4-year study period, 317 consecutive pts were diagnosed with de novo or transformed DLBCL or BCLU. Twenty-one (7%) showed a translocation of MYC, in single (14%), double (67%) or triple hit (19%), with respect to BCL2 and BCL6 rearrangements. Interestingly, 8 (2.5%) pts with no MYC translocation showed MYC ICN, ranging from 3 up to 10 gene copies per cell. This aberrant gene copy number was observed in > 80% of the analyzed nuclei in 7 cases. The characteristics of the pts with MYC gene rearrangement or ICN are summarized in Table 1.
Of the 8 pts with MYC ICN, 5 had de novo DLBCL, 2 had transformed DLBCL and 1 had BCLU. Seven pts also showed BCL2 and/or BCL6 rearrangement/ICN. Three pts were treated with standard ICT and 5 with a BLlike regimen. Two pts (25%) responded to the FLT, showing one complete and one partial remission (CR and PR, respectively); both received BLlike regimen. The patient with PR progressed after 7 months, and received a second line treatment likewise the 6 nonresponders to FLT. None of them had a response and eventually died, with a median OS of 10.5 months. Cause of death was lymphoma in all cases. The patient who obtained a CR was still in remission at 29 months from the end of the FLT. The survival of these pts, compared to pts with MYC rearrangement, is shown in Figure 1 (respectively 12% vs 57% at 2 years, p 0.04).
Conclusion: These preliminary data show a dismal prognosis of pts with aggressive B cell lymphoma and MYC ICN, significantly worse than pts harboring a MYC translocation, independently of the treatment received. To better understand the genetic defect underlying this FISH pattern, further analysis using a specific centromere probe for chromosome 8 is ongoing on these and new cases. A previous study distinguished gain from amplification of MYC based on the number of gene copies, identifying 2 groups with different prognosis (Valera, Hematologica 2013). In our hands, there was a wider range of gene copy number in each patient, and the outcome was homogeneously poor. Overall, the biological consequence of this alteration is still to be fully explained, and only a few studies have addressed this point so far (Stasik, Hematologica 2010). Further investigation on larger cohort groups is necessary to confirm the unfavorable prognostic role of MYC ICN in aggressive B cell lymphoma. Such insights would help practitioners to determine more accurate therapeutic approaches, in order to improve the outcome of this specific subset of pts.
Display omitted Display omitted
No relevant conflicts of interest to declare.
Introduction. Invasive pulmonary aspergillosis (IPA) remains a major clinical issue in Acute Leukemia (AL) patients (pts) and can affect the outcome of hematological treatment. Acute Myeloid Leukemia ...(AML) is considered the most frequent hematological condition predisposing to IPA; however, the introduction of posaconazole prophylaxis has significantly reduced IPA during AML induction. On the other hand, incidence of IPA among Acute Lymphoblastic Leukemia (ALL) pts seems to be increasing. In order to confirm these epidemiological data and to analyze the impact of IPA on the outcome of AL, we analyzed all AML and ALL pts consecutively admitted to our Institution during a 5-year period of observation. Patients and Methods. From Jul-11 to Jun-16, all consecutive AML and ALL pts admitted to our Institution and treated with intensive chemotherapy were analyzed. IPA was diagnosed according to EORTC/MSG criteria and categorized as possible (poss) and probable/proven (p/p). Anti-mold prophylaxis (posaconazole) was always administered during induction/reinduction only in AML pts. CT scan was performed in case of persisting neutropenic fever for 3 days despite broad-spectrum antibiotic therapy. The effects of age, gender, type of AL, disease risk (ELN 2010 for AML, ESMO 2016 for ALL) and status complete remission (CR), relapse/refractory (Rel/Refr), IPA, allogeneic stem cell transplantation (alloSCT) on outcome were evaluated. Results. During the 5-year period, 175 AL patients were observed (136 AML/39 ALL; median age 55, range 14-74; M/F ratio 6/5). Overall, 28 (16%) IPA were diagnosed, 11 (6.3%) poss and 17 (9.7%) p/p. Frequency was similar in AML (22/136, 16.2%) and in ALL pts (6/39, 15.4%,) but p/p IPA were relatively more frequent in ALL (83%) (1 poss, and 5 p/p) than in AML (54.5%) (10 poss and 12 p/p). Considering the disease phase, IPA occurred in 8% of 175 pts during induction, in 4.4% of 159 pts during consolidation and in 13.5% of 52 pts during reinduction. The frequency of IPA, particularly p/p, observed during induction was lower in AML (10/22, 45%; 5 poss and 5 p/p) than in ALL (4/6, 67%, all p/p). More than half of the IPA observed in AML were recorded in phases different from induction (6 during consolidation and 6 during reinduction). Median time from AL diagnosis to IPA was 2.5 mo (range 0-26) in AML and 1 mo (0-6) in ALL (p=0.089). After a median follow-up of 36 mo (range 4-68), 69 pts died: 12 (17.4%) of refractory AL and concomitant IPA and 2 (2.9%) of IPA while on CR. Thirteen pts with previous IPA underwent alloSCT; 9 (69.2%, 6/8 poss and 3/5 p/p IPA) died, as compared to 24 of 65 (36.9%) pts transplanted without a history of IPA (p=0.03). AL 2-year overall survival (OS) was significantly affected by the development of IPA, with no differences between poss and p/p IPA (no IPA 71.9% vs poss IPA 36.4% or p/p IPA 33.1%; p=0.0003 and <0.0001, respectively) (Fig. 1a). Figures are similar when considering AML and ALL separately (no IPA 66.7% vs poss IPA 40% or p/p IPA 33%, p=0.016 and <0.0042; no IPA 87.5% vs IPA 25%, p=0.0005, respectively for AML and ALL). Notably, after excluding the role of alloSCT by censoring pts at transplant (median follow-up 14.5 mo; range 2-68), poss IPA had no effect, whereas p/p IPA was associated with lower survival (at 2 years: p/p IPA 33.6% vs no IPA 80.6% or poss IPA 85.7%; p=0.0003 and 0.0004, respectively) (Fig. 1b). Multivariate analysis confirmed that developing IPA was an independent risk factor for OS (OR 3.4, CI 1.2-9.4), together with age≥60y (2.19, 1.01-4.74) and having Rel/Refr AL (9.41, 4.34-20.4), whereas achieving CR after 1st induction was protective (0.15, 0.05-0.45). Only p/p IPA was a risk factor for mortality, when excluding the effect of alloSCT (5.06, 1.63-15.65). Conclusions. These data confirm that IPA still affects a considerable proportion of AL pts and that its frequency has become high even in ALL patients, where it occurs early during induction and mainly as p/p IPA, probably because of the more intensive chemotherapeutic regimens containing dexametasone and of the lack of anti-mold prophylaxis. Therefore, anti-mold prophylaxis should be recommended also in ALL patients during induction. In AL pts not undergoing alloSCT, only those with p/p IPA have a poor prognosis; however having a poss IPA negatively impacts on OS when considering the entire series, including alloSCT pts.
Display omitted
Rossi:Roche: Membership on an entity's Board of Directors or advisory committees; Janssen: Membership on an entity's Board of Directors or advisory committees; Amgen: Membership on an entity's Board of Directors or advisory committees; AbbVie: Membership on an entity's Board of Directors or advisory committees; Celgene: Membership on an entity's Board of Directors or advisory committees; Teva: Membership on an entity's Board of Directors or advisory committees; Gilead: Membership on an entity's Board of Directors or advisory committees; Sanofi: Membership on an entity's Board of Directors or advisory committees.
Background: According to the WHO classification, secondary acute myeloid leukemia (s-AML) includes cases occurring in patients (pts) receiving prior antineoplastic treatments as well as cases ...developing in pts with a history of previous hematology disorders, such as a myelodysplastic syndrome (MDS) or a chronic myeloproliferative disease (MPD).
Outcomes for this large group of pts, which has a high median age and a high frequency of unfavourable cytogenetics, has been traditionally considered very poor, compared to AML developing “de novo”, and treatment with intensive chemotherapy (iCT) is not standardized in elderly pts. Indeed pts with s-AML have been excluded from molecular and cytogenetic prognostic stratification defined by the ELN criteria.
Aim: Since patients with s-AML actually represent an heterogeneous subgroup of pts a multicenter retrospective study was performed to analyse their outcome in relationship to age, fitness and ELN risk stratification, in order to potentially identify subgroups at different prognosis.
Patients and Methods: We evaluated 127 pts, representing 35% of a population-based series of elderly AML, aged > 65 years (y), diagnosed at five Hematology Centers of the Hematological Network of Lombardy in Northern Italy from January 2008 to May 2014. Thirteen pts (10%) had t-AML and 114 (90%) had AML secondary to previous hematological disorders (89 MDS and 25 MPD). Median age was 74 y (range 65-94 y). Performance status (PS) was evaluable in 122 pts (96%) and PS ECOG was >3 in 32 pts (26%). According to “fitness criteria”, (Ferrara et al, Leukemia, 2013), 126 pts (99%) were evaluable: 54 pts (42.5%) were fit to i-CT (FIT), 55 (43.3%) unfit to i-CT (UNFIT), 17 (13.4%) unfit to ni-CT (FRAIL). Intensive CT was given to 34 (27%), ni-CT (low-dose arac, azacytidine or experimental non-myelotoxic drugs) to 26 (20%) and best supportive care (BSC) to 67 pts (53%). Overall concordance between the fitness and the treatment actually received was 78%.The ELN prognostic criteria were applicable in 69 pts (54%), because of lack of complete molecular and cytogenetic data in the others. Six pts (8.5%, all NPM1+) were at low, 14 (20%) at intermediate-1, 11 (16%) at intermediate-2 and 38 (55%) at high risk.
Results: The median OS according to fitness was 9,6, 4 and 3 months (ms), in FIT, UNFIT and FRAIL pts, respectively (p=0.0021) (Figure 1). Both the treatment received (i-CT or ni-CT vs BSC) and the risk ELN classification were related to OS (p< 0.0001 and p=0.0089, respectively). In FIT pts the median OS was 8 ms in pts treated with i-CT, 11 ms with ni-CT, and 3 ms with BSC (p<0.0001) (i-CT vs ni-CT : p=0.6) (Figure2).
The achievement of CR was related to outcome (median OS 12.7 ms vs 5 ms) (p= 0.0035). AML with antecedent hematological disorder (53.8%) or with t-AML (50%) had similar CR rate (53,8% vs 50%) as well as OS (median OS 11 ms vs 7 ms) (p =0.5).
According to ELN risk, OS was better in LR/Int-1/int2 vs HR (median OS 11,4 vs 5 ms, p=0.0035) (Figure 2).
Moreover, also the achievement of CR was related to ELN risk: 100% in LR, 57% in Int1/Int2, 14% in HR (p= 0.012), and percentages differed from de novo AML only in HR pts. Prognosis of the subgroup of 34 ELN low/Int1 risk pts treated with i-CT was fair with CR rate of 53%, and 2 y OS 40% compared to 10% in similarly treated Int2/HR pts (p=0.07).
Conclusion: Elderly pts with s-AML are an heterogeneous subgroup both according to fitness and to ELN risk stratification and these parameters are significantly related to clinical outcome. Overall prognosis of elderly patients with s-AML is not exceedingly worse than in elderly with de novo AML. Outcome was better using i-CT or ni-CT compared to BSC, with no differences between the two treatment modalities. ELN risk stratification merits to be applied also to patients with s-AML and its integration with fitness criteria can identify a subgroup of patients which may benefit from intensive CT.
Display omitted
Display omitted
No relevant conflicts of interest to declare.
Nodular lymphocyte‐predominant Hodgkin lymphoma (NLPHL) is a rare entity whose neoplastic cells retain a B‐cell phenotype with expression of CD20. Radiotherapy is recommended for favorable stage IA ...disease while for other stages guidelines suggest therapeutic strategies similar to those used for classic HL. The role of rituximab, although quite widespread, is not completely elucidated. We retrospectively analyzed baseline characteristics of 308 consecutive patients with NLPHL diagnosed in 19 Italian centers from 2000 to 2018. With a median follow‐up of 8.4 years (interquartile range: 4.5–12.4) for treated patients, median overall survival (OS) was not reached and estimated 5‐year OS was 97.8% and 5‐year progression‐free survival (PFS) was 84.5%. Five‐year cumulative incidence of histological transformation was 1.4%, 95% confidence interval (CI), 0.5%‐3.8%. After adjusting for lymphocyte count, splenic involvement, bulky disease and B symptoms (fever, drenching night sweats, unintentional loss >10% of body weight within the preceding 6 months), patients with stage II or more showed superior PFS with immunochemotherapy in comparison to chemotherapy alone (hazard ratio = 0.4, 95% CI, 0.2‐0.8; P = 0.015). Our data suggest an advantage of the use of rituximab combined with chemotherapy ± radiotherapy in the treatment of stage II–III–IV NLPHL.
PDF
