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1.
Hematol Oncol ; 42(4): e3289, 2024 Jul.
Article in English | MEDLINE | ID: mdl-38824453

ABSTRACT

Daratumumab-based regimens are the new standard of care for newly diagnosed patients with AL amyloidosis based on the results of the ANDROMEDA study. However, real-world data on daratumumab efficacy in upfront therapy in unselected patients are scanty. In the framework of a prospective observational study, we investigated the efficacy and safety of daratumumab in 88 newly diagnosed patients, including subjects with IIIb cardiac stage (26%) or myeloma defining events (29%). Daratumumab was administered with bortezomib in 50 (56%) patients, lenalidomide in 31 (35%), and monotherapy in 7 (8%). The rate of serious adverse events was low (16%). The overall hematologic response rate was 75% with 52 (59%) patients attaining at least a very good partial response (VGPR) at six months. Amongst patients evaluable for organ response, the rate of cardiac and renal responses at 6 months was 31% and 21%, respectively. Comparing stage IIIb patients with the remaining ones, the rate of profound hematologic response was not significantly different (≥VGPR 57% vs. 59%, p 0.955) likewise the rate of cardiac (33% vs. 30%, p 0.340) and renal (40% vs. 16%, p 0.908) responses. Daratumumab-based regimens demonstrated to be safe and effective in treatment-naïve AL amyloidosis even in advanced stage disease.


Subject(s)
Antibodies, Monoclonal , Antineoplastic Combined Chemotherapy Protocols , Immunoglobulin Light-chain Amyloidosis , Humans , Male , Female , Antibodies, Monoclonal/administration & dosage , Antibodies, Monoclonal/therapeutic use , Antibodies, Monoclonal/adverse effects , Aged , Immunoglobulin Light-chain Amyloidosis/drug therapy , Immunoglobulin Light-chain Amyloidosis/diagnosis , Middle Aged , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Antineoplastic Combined Chemotherapy Protocols/adverse effects , Aged, 80 and over , Prospective Studies , Lenalidomide/administration & dosage , Lenalidomide/therapeutic use , Lenalidomide/adverse effects , Bortezomib/administration & dosage , Bortezomib/therapeutic use , Bortezomib/adverse effects , Adult , Treatment Outcome
2.
Eur J Haematol ; 111(6): 922-929, 2023 Dec.
Article in English | MEDLINE | ID: mdl-37747757

ABSTRACT

BACKGROUND: Gaucher disease (GD) is a rare autosomal recessive inherited disorder caused by the lysosomal enzyme acid ß-glucosidase deficiency. Many patients experience a critical delay in the diagnosis of up to 8-10 years due to its rarity and variability in signs and symptoms, with the consultation of several specialists. PATIENTS AND METHODS: This prospective observational study analyzed the prevalence of GD in 600 patients with monoclonal gammopathy of uncertain significance (MGUS) from January 2018 until February 2022. RESULTS: The mean age of participants was 66 years, with a mean monoclonal component of 0.58 g/dL. In 433 MGUS patients with available data, anemia (hemoglobin level < 10 g/dL) was present in 31 patients (7%), and thrombocytopenia (platelet count <100.000/mm3 ) in 24 (5.5%). Of 600 MGUS patients tested for acid ß-glucosidase enzyme activity, 7 patients (1.2%) had activity below 2.5 nmol/h/mL. In comparison, GBA gene analysis was executed in 110 patients. It revealed 4 patients (0.7%) affected by GD (3 patients with compound heterozygous mutation and 1 with homozygous mutation), with a prevalence of 1 every 150 MGUS patients. Furthermore, 12 out of the remaining 106 evaluated patients (11%) were carriers of a single heterozygous mutation while having regular enzyme activity. CONCLUSIONS: The clinical heterogeneity of GD and frequent lack of awareness among physicians often lead to diagnostic delays and severe clinical manifestations. The role of MGUS in the presence of at least one clinical sign, such as low platelet count, organomegaly, bone pain, or bleeding tendency, could aid in initiating GD screening with DBS, thus reducing the period between symptom onset and the diagnosis of this rare disease.


Subject(s)
Anemia , Gaucher Disease , Monoclonal Gammopathy of Undetermined Significance , Paraproteinemias , Humans , Aged , Monoclonal Gammopathy of Undetermined Significance/complications , Monoclonal Gammopathy of Undetermined Significance/diagnosis , Monoclonal Gammopathy of Undetermined Significance/epidemiology , Gaucher Disease/complications , Gaucher Disease/diagnosis , Gaucher Disease/epidemiology , Prevalence
3.
Case Rep Hematol ; 2023: 9953245, 2023.
Article in English | MEDLINE | ID: mdl-37323813

ABSTRACT

Immune thrombocytopenia (ITP) is immune-mediated platelet loss due to increased destruction and insufficient production. Treatment guidelines provide for first-line steroid-based therapies followed by thrombopoietin receptor agonists (TPO-RAs) and fostamatinib for chronic ITP. Fostamatinib demonstrated efficacy in phase 3 FIT trials (FIT1 and FIT2) mainly in second-line therapy resulting in the maintenance of stable platelet values. Here, we describe two patients with extremely heterogeneous characteristics that responded to fostamatinib after two and nine previous treatments. Responses were complete with stable platelet counts ≥50,000/µL and without any grade ≥3 adverse reactions. As in the FIT clinical trials, we confirm better responses to fostamatinib when used in the second or third line. However, its use should not be excluded in patients with longer and more complicated drug histories. Given the different mechanism of action of fostamatinib compared to TPO-RAs, it would be interesting to identify predictive factors of responsiveness applicable to all patients.

4.
Mediterr J Hematol Infect Dis ; 15(1): e2023019, 2023.
Article in English | MEDLINE | ID: mdl-36908864

ABSTRACT

Background: Two thrombopoietin receptor agonists (TPO-RA), romiplostim and eltrombopag, are currently widely adopted as second-line ITP therapy even in the absence of robust evidence on their comparative advantages over rituximab or splenectomy or their preferential use in some specific clinical contexts. Methods: An online survey was distributed between May 2021 and June 2021 to collect standardized information on TPO-RA use in Italy. Results: Eighty-eight hematologists from 79 centers completed the survey. Eighty-four percent would use TPO-RA earlier than formally indicated, without a preference for young or elderly in 82% of respondents. No clear preference for either romiplostim or eltrombopag was indicated. Seventy-two percent would use TPO-RA in young patients aiming at a complete response followed by tapering, a strategy considered by only 16% in the elderly. Switching between the two agents was considered appropriate in case of insufficient response or intolerance. Tapering schedule by reducing the dosage and prolonging the intervals between administrations was preferred by 73% of respondents. TPO-RA was considered a risk factor for thrombosis by only 35%, and 94% would administer TPO-RA in elderly patients also in the presence of other thrombotic risk factors. Thirty-three percent of respondents would withdraw TPO-RA in case of thrombosis. The TPORA administration has been reported to be preferred over anti-CD20 or splenectomy by about half of the participants due to the ongoing COVID-19 pandemic. Conclusions: Significant discrepancies in TPO-RA use emerged from the survey, and participants would appreciate consensus-based specific guidance on the practical use of TPO-RA.

5.
Pathogens ; 12(2)2023 Feb 12.
Article in English | MEDLINE | ID: mdl-36839576

ABSTRACT

Hematological diseases, especially those causing severe neutropenia, represent the main factor in the development of invasive fungal infections (IFIs). Furthermore, COVID-19 has been considerably associated with IFIs due to immunological dysregulation, prolonged hospitalization in intensive care units, and immunomodulatory therapies. Opportunistic molds are correlated with elevated morbidity and mortality rates in these patients, due to immune impairment, diagnostic complexity, and therapeutic challenges. Among opportunistic fungal infections, the Mucorales and Fusarium species are considered particularly aggressive, especially during severe neutropenia. A mixed Mucorales/Fusarium infection has been rarely described in scientific literature. Herein, we report a case of Mucorales and Fusarium co-infection in a patient with acute leukemia whose clinical history was also complicated by COVID-19. Herein, we report a challenging case in order to encourage the clinical suspicion of combined fungal infections in immunosuppressed patients, performing a punctual microbiological diagnosis, and promptly administering the correct empiric and targeted antifungal therapy.

6.
Hematol Oncol ; 40(4): 704-715, 2022 Oct.
Article in English | MEDLINE | ID: mdl-35608183

ABSTRACT

The combination of elotuzumab, lenalidomide, and dexamethasone (EloRd) enhanced the clinical benefit over Rd with a manageable toxicity profile in the ELOQUENT-2 trial, leading to its approval in relapsed/refractory multiple myeloma (RRMM). The present study is a 3-year follow-up update of a previously published Italian real-life RRMM cohort of patients treated with EloRd. This revised analysis entered 319 RRMM patients accrued in 41 Italian centers. After a median follow-up of 36 months (range 6-55), 236 patients experienced disease progression or died. Median progression-free survival (PFS) and overall survival (OS) were 18.4 and 34 months, respectively. The updated multivariate analyses showed a significant reduction of PFS and OS benefit magnitude only in cases with International Staging System stage III. Major adverse events included grade 3/4 neutropenia (18.5%), anemia (15.4%), lymphocytopenia (12.5%), and thrombocytopenia (10.7%), while infection rates and pneumonia were 33.9% and 18.9%, respectively. No new safety signals with longer follow-up have been observed. Of 319 patients, 245 (76.7%) reached at least a partial remission. A significantly lower response rate was found in patients previously exposed to lenalidomide. In conclusion, our study confirms that EloRd is a safe and effective regimen for RRMM patients, maintaining benefits across multiple unfavorable subgroups.


Subject(s)
Multiple Myeloma , Antibodies, Monoclonal, Humanized , Antineoplastic Combined Chemotherapy Protocols/adverse effects , Dexamethasone/adverse effects , Follow-Up Studies , Humans , Lenalidomide/therapeutic use , Retrospective Studies , Thalidomide/adverse effects
7.
Adv Hematol ; 2022: 5581772, 2022.
Article in English | MEDLINE | ID: mdl-35126524

ABSTRACT

Subcutaneous (SC) rituximab may be beneficial in terms of convenience and tolerability, with potentially fewer and less severe administration-related reactions (ARRs) compared to the intravenous (IV) form. This report presents the results of a phase IIIb study conducted in Italy. The study included adult patients with CD20+ DLBCL or FL having received at least one full dose of IV RTX 375 mg/m2 during induction or maintenance. Patients on induction received ≥4 cycles of RTX SC 1400 mg plus standard chemotherapy and FL patients on maintenance received ≥6 cycles of RTX SC. Overall, 159 patients (73 DLBCL, 86 FL) were enrolled: 103 (54 DLBCL, 49 FL) completed induction and 42 patients with FL completed 12 maintenance cycles. ARRs were reported in 10 patients (6.3%), 3 (4.2%) with DLBCL and 7 (8.1%) with FL, all of mild severity, and resolved without dose delay/discontinuation. Treatment-emergent adverse events (TEAEs) and serious adverse events occurred in 41 (25.9%) and 14 patients (8.9%), respectively. Two patients with DLBCL had fatal events: Klebsiella infection (related to rituximab) and septic shock (related to chemotherapy). Neutropenia (14 patients, 8.9%) was the most common treatment-related TEAE. Two patients with DLBCL (2.8%) and 6 with FL (7.0%) discontinued rituximab due to TEAEs. 65.2% and 69.7% of patients with DLBCL and 67.9% and 73.6% of patients with FL had complete response (CR) and CR unconfirmed, respectively. The median time to events (EFS, PFS, and OS) was not estimable due to the low rate of events. At a median follow-up of 29.5 and 47.8 months in patients with DLBCL and FL, respectively, EFS, PFS, and OS were 70.8%, 70.8%, and 80.6% in patients with DLBCL and 77.9%, 77.9%, and 95.3% in patients with FL, respectively. The switch from IV to SC rituximab in patients with DLBCL and FL was associated with low risk of ARRs and satisfactory response in both groups. This trial was registered with NCT01987505.

9.
Surg Neurol Int ; 12: 387, 2021.
Article in English | MEDLINE | ID: mdl-34513154

ABSTRACT

BACKGROUND: Burkitt's lymphoma is a non-Hodgkin B-cell lymphoma, occurring mostly in Equatorial Africa. According to the WHO, classification is three different variants: sporadic, endemic, and immunodeficient-associated. Here, we present a patient with "sporadic" primary epidural Burkitt's lymphoma resulting in chronic low back pain (LBP). CASE DESCRIPTION: A 63-year-old female presented with a 2-month history of LBP and the left lower extremity sciatica. The thoracolumbar MRI showed a L5 irregular, osteolytic epidural lesion that was hypointense on T1-weighted images, hyperintense on STIR studies, and inhomogeneously enhanced with contrast. Additional hypointense lesions were also seen at the L2, L3, and L4 levels. The patient underwent a L4-L5 laminectomy for piecemeal epidural resection of tumor, and a L4-S1 transpedicular screws/rod fusion. In addition, a L2-L3 radiofrequency ablation was performed. The histological examination documented a primary "sporadic" spinal Burkitt's lymphoma. The patient subsequently was treated with both radiotherapy/chemoradiotherapy. CONCLUSION: Primary "sporadic" spinal Burkitt's lymphoma is rare. Following tumor resection, adjunctive radiation and chemotherapy are typically warranted.

10.
Ann Hematol ; 100(10): 2547-2556, 2021 Oct.
Article in English | MEDLINE | ID: mdl-34327561

ABSTRACT

We investigated the feasibility and activity of an intensified dose-dense ABVD (dd-ABVD) regimen in patients with early-stage unfavorable Hodgkin lymphoma (HL). This prospective, multicenter, phase II study enrolled 96 patients with newly diagnosed, unfavorable stage I or II classical HL. The patients received four cycles of dd-ABVD followed by radiotherapy. Interim PET (PET-2) was mandatory after two courses. Primary endpoints were the evaluation of dd-ABVD feasibility and activity (incidence of PET-2 negativity). The feasibility endpoint was achieved with 48/52 (92.3%) patients receiving > 85% of the programmed dose. The mean dose intensity in the overall patient population (n = 96) was 93.7%, and the median duration of dd-ABVD was 85 days (range, 14-115) versus an expected duration of 84 days. PET-2 was available for 92/96 (95.8%) patients, of whom 79 were PET-2 negative (85.9%). In total, 90 (93.8%) patients showed complete response at the end of treatment. With a follow-up of 80.9 months (3.3-103.2), the median progression-free survival (PFS) and overall survival (OS) were not reached. At 84 months, PFS and OS rates were 88.4% and 95.7%, respectively. No evidence for a difference in PFS or OS was observed for PET-2-negative and PET-2-positive patients. Infections were documented in 8.3% and febrile neutropenia in 6.2% of cases. Four patients died: one had alveolitis at cycle 3, one death was unrelated to treatment, and two died from a secondary cancer. dd-ABVD is feasible and demonstrates activity in early-stage unfavorable HL. The predictive role of PET-2 positivity in early-stage unfavorable HL remains controversial. The study was registered in the EudraCT (reference number, 2011-003,191-36) and the ClinicalTrials.gov (reference number, NCT02247869) databases.


Subject(s)
Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Hodgkin Disease/drug therapy , Adult , Antineoplastic Combined Chemotherapy Protocols/administration & dosage , Bleomycin/administration & dosage , Bleomycin/therapeutic use , Dacarbazine/administration & dosage , Dacarbazine/therapeutic use , Dose-Response Relationship, Drug , Doxorubicin/administration & dosage , Doxorubicin/therapeutic use , Female , Hodgkin Disease/epidemiology , Humans , Italy/epidemiology , Male , Middle Aged , Progression-Free Survival , Prospective Studies , Treatment Outcome , Vinblastine/administration & dosage , Vinblastine/therapeutic use , Young Adult
12.
Blood ; 138(7): 571-583, 2021 08 19.
Article in English | MEDLINE | ID: mdl-33889952

ABSTRACT

The efficacy and safety of thrombopoietin receptor agonists (TRAs) in older patients with primary immune thrombocytopenia (ITP) are unknown. We investigated TRA response and switch, thrombotic/hemorrhagic risk, and sustained responses off-treatment (SROTs) in 384 patients with ITP aged ≥60 years. After 3 months, 82.5% and 74.3% of eltrombopag- and romiplostim-treated patients, respectively, achieved a response; 66.7% maintained the response (median follow-up, 2.7 years). Eighty-five (22.2%) patients switched to the alternative TRA; although no cross-toxicity was observed, 83.3% of resistant patients had a response after the switch. Thirty-four major thromboses (3 fatal) and 14 major hemorrhages (none fatal) occurred in 18 and 10 patients, respectively, while on TRAs and were associated with thrombosis history (subdistribution hazard ratio, 2.04, P = .05) and platelet count <20 × 109/L (subdistribution hazard ratio, 1.69; P = .04), respectively, at TRA start. A recurrent event occurred in 15.6% of patients surviving thrombosis, in all cases but 1 during persisting TRA treatment (incidence rate, 7.7 per 100 patient-years). All recurrences occurred in the absence of adequate antithrombotic secondary prophylaxis. Sixty-two (16.5%) responding patients discontinued TRAs; 53 (13.8%) patients maintained SROTs, which were associated with TRA discontinuation in complete response (P < .001). Very old age (≥75 years; 41.1%) was associated with the more frequent start of TRAs in the persistent/acute phase but not with response or thrombotic/hemorrhagic risk. TRAs are effective in older patients with ITP, with no fatal hemorrhages and with SROTs in a significant portion of patients. Caution is warranted in patients with a history of thrombosis, and a careful risk/benefit balance should be considered.


Subject(s)
Benzoates , Hydrazines , Purpura, Thrombocytopenic, Idiopathic , Pyrazoles , Receptors, Fc , Receptors, Thrombopoietin/antagonists & inhibitors , Recombinant Fusion Proteins , Thrombopoietin , Thrombosis , Aged , Aged, 80 and over , Benzoates/administration & dosage , Benzoates/adverse effects , Female , Follow-Up Studies , Hemorrhage/chemically induced , Hemorrhage/epidemiology , Humans , Hydrazines/administration & dosage , Hydrazines/adverse effects , Male , Middle Aged , Purpura, Thrombocytopenic, Idiopathic/drug therapy , Purpura, Thrombocytopenic, Idiopathic/mortality , Pyrazoles/administration & dosage , Pyrazoles/adverse effects , Receptors, Fc/administration & dosage , Recombinant Fusion Proteins/administration & dosage , Recombinant Fusion Proteins/adverse effects , Retrospective Studies , Thrombopoietin/administration & dosage , Thrombopoietin/adverse effects , Thrombosis/chemically induced , Thrombosis/mortality
13.
Am J Hematol ; 96(8): E269-E272, 2021 08 01.
Article in English | MEDLINE | ID: mdl-33878220
14.
Am J Hematol ; 96(5): E168-E171, 2021 05 01.
Article in English | MEDLINE | ID: mdl-33580969
15.
Br J Haematol ; 193(2): 386-396, 2021 04.
Article in English | MEDLINE | ID: mdl-33618438

ABSTRACT

Up to 30% immune thrombocytopenia (ITP) patients achieve a sustained remission off-treatment (SROT) after discontinuation of thrombopoietin receptor agonists (TPO-RAs). Factors predictive of response are lacking. Patients aged ≥18 years with newly diagnosed or persistent ITP were treated with eltrombopag for 24 weeks. Primary end-point was SROT: the proportion of responders that were able to taper and discontinue eltrombopag maintaining the response during a period of observation (PO) of six months. Secondary end-points included the association between some immunological parameters (TPO serum levels, cytokines and lymphocyte subsets) and response. Fifty-one patients were evaluable. Primary end-point was achieved in 13/51 (25%) treated patients and 13/34 (38%) patients who started the tapering. Baseline TPO levels were not associated with response at week 24 nor with SROT. Higher baseline levels of IL-10, IL-4, TNF-α and osteopontin were negative factors predictive of response (P = 0·001, 0·008, 0·02 and 0·03 respectively). This study confirms that SROT is feasible for a proportion of ITP patients treated with eltrombopag. Some biological parameters were predictive of response.


Subject(s)
Benzoates/therapeutic use , Drug Tapering/statistics & numerical data , Hydrazines/therapeutic use , Purpura, Thrombocytopenic, Idiopathic/drug therapy , Pyrazoles/therapeutic use , Receptors, Thrombopoietin/agonists , Adult , Aged , Aged, 80 and over , Benzoates/administration & dosage , Benzoates/toxicity , Cytokines/immunology , Drug Tapering/methods , Female , Humans , Hydrazines/administration & dosage , Hydrazines/toxicity , Lymphocytes/immunology , Male , Middle Aged , Predictive Value of Tests , Prospective Studies , Purpura, Thrombocytopenic, Idiopathic/diagnosis , Pyrazoles/administration & dosage , Pyrazoles/toxicity , Receptors, Thrombopoietin/immunology , Remission Induction , Withholding Treatment/statistics & numerical data
16.
Ann Hematol ; 100(3): 653-659, 2021 Mar.
Article in English | MEDLINE | ID: mdl-33495923

ABSTRACT

The primary aim of this study was to describe the use of primary anti-infective prophylaxis (AP) in common clinical practice in patients affected by immune thrombocytopenia (ITP) and treated with RTX. Population studied consisted of patients affected by ITP (age ≥ 18 years) who had received at least one dose of RTX from January 2008 to June 2018. Five Italian haematology centres participated in the current study. Data were retrospectively collected: demographic data (age, gender), concomitant comorbidities and previous therapies for ITP, characteristics of AP, the occurrence of infections and their management. The ITP cohort consisted of 67 patients sub-grouped into two categories according to the administration of AP: (1) treated with AP (N= 34; 51%) and (2) not treated with AP (N=33, 49%). AP consisted of combined trimethoprim/sulfamethoxazole (TMP/SMX) and acyclovir (AC) in half of patients. TPM/SMX as a single agent was adopted in 32% patients and one patient received only AC. Overall, infections were experienced in 15% of patients during follow-up with a similar proportion in the 2 groups (treated and not treated) of patients (14.7% vs 15%). Clinical course of infections was however, less severe in patients treated with AP, where all infections were grade 2 and did not require hospitalization. In neither group of patients was reported Pneumocystis pneumonia. In conclusion, despite the absence of clear evidence, our analysis shows that AP in patients with ITP receiving RTX is frequently adopted, even if in the absence of well-defined criteria. Prophylaxis administration is quite consistent within the same haematological Center; thus, it seems related to clinicians' experience.


Subject(s)
Antibiotic Prophylaxis , Opportunistic Infections/drug therapy , Practice Patterns, Physicians'/statistics & numerical data , Purpura, Thrombocytopenic, Idiopathic/drug therapy , Rituximab/therapeutic use , Adolescent , Adult , Aged , Aged, 80 and over , Antibiotic Prophylaxis/methods , Antibiotic Prophylaxis/statistics & numerical data , Female , Humans , Italy/epidemiology , Male , Middle Aged , Opportunistic Infections/epidemiology , Opportunistic Infections/etiology , Purpura, Thrombocytopenic, Idiopathic/complications , Purpura, Thrombocytopenic, Idiopathic/epidemiology , Retrospective Studies , Young Adult
17.
Haematologica ; 106(1): 291-294, 2021 01 01.
Article in English | MEDLINE | ID: mdl-32107338
18.
Leukemia ; 35(1): 235-238, 2021 01.
Article in English | MEDLINE | ID: mdl-32286543
19.
Eur J Haematol ; 106(4): 493-499, 2021 Apr.
Article in English | MEDLINE | ID: mdl-33378569

ABSTRACT

OBJECTIVES: To compare the capacity of ibrutinib (IB) and idelalisib-rituximab (IDELA-R) of prolonging overall survival (OS) as in CLL patients, previously treated with chemotherapy only. METHODS: A real-life cohort of 675 cases has been identified and investigated in the database of the groups participating in the study. RESULTS: At an unadjusted univariate analysis, a significant death risk reduction was observed favoring IB (IDELA-R vs IB HR = 0.5, 95% CI = 0.36-0.71) although with some limitations due to the non-randomized and retrospective nature of the study and to the lower number of patients in the IDELA-R group (112 cases) related to the current prescribing practice. To overcome the potential problem of confounding by indication, we adjusted the association between the type of therapy and mortality for all variables significantly associated with OS at Cox univariate analysis. Furthermore, those variables, differently distributed between the two study groups, were introduced into the multivariate Cox model to improve the effectiveness of the analysis. By introducing all these variables into the multiple Cox regression model, we confirmed the protective effect of IB vs IDELA-R (HR = 0.67, 95% CI = 0.45-0.98, P = .04) independent of potential confounders. CONCLUSIONS: Although our analysis presents some constraints, that is, the unavailability of additional potential confounders, and the retrospective nature of the study, this observation may be of help for the daily clinical practice, particularly in the absence of randomized trials comparing the two schedules.


Subject(s)
Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Leukemia, Lymphocytic, Chronic, B-Cell/drug therapy , Adenine/administration & dosage , Adenine/analogs & derivatives , Aged , Aged, 80 and over , Antineoplastic Combined Chemotherapy Protocols/adverse effects , Biomarkers, Tumor , Drug Resistance, Neoplasm , Female , Humans , Immunoglobulins/genetics , In Situ Hybridization, Fluorescence , Leukemia, Lymphocytic, Chronic, B-Cell/diagnosis , Leukemia, Lymphocytic, Chronic, B-Cell/etiology , Leukemia, Lymphocytic, Chronic, B-Cell/mortality , Male , Middle Aged , Mutation , Piperidines/administration & dosage , Proportional Hazards Models , Purines/administration & dosage , Quinazolinones/administration & dosage , Recurrence , Retreatment , Rituximab/administration & dosage , Treatment Outcome
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