Chlorambucil plus rituximab with or without maintenance rituximab as first-line treatment for elderly chronic lymphocytic leukemia patients.

In a phase II trial, we evaluated chlorambucil and rituximab (CLB-R) as first-line induction treatment with or without R as maintenance for elderly chronic lymphocytic leukemia (CLL) patients. Treatment consisted of eight 28-day cycles of CLB (8 mg/m(2) /day, days 1-7) and R (day 1 of cycle 3, 375 mg/m(2) ; cycles 4-8, 500 mg/m(2) ). Responders were randomized to 12 8-week doses of R (375 mg/m(2) ) or observation. As per intention-to-treat analysis, 82.4% (95% CI, 74.25-90.46%) of 85 patients achieved an overall response (OR), 16.5% a complete response (CR), 2.4% a CR with incomplete bone marrow recovery. The OR was similar across Binet stages (A 86.4%, B 81.6%, and C 78.6%) and age categories (60-64 years, 92.3%; 65-69, 85.2%; 70-74, 75.0%; ≥75, 81.0%). CLB-R was well tolerated. After a median follow-up of 34.2 months, the median progression-free survival (PFS) was 34.7 months (95% CI, 33.1-39.5). TP53 abnormalities, complex karyotype, and low CD20 gene expression predicted lack of response; SF3B1 mutation and BIRC3 disruption low CR rates. IGHV mutations significantly predicted PFS. R maintenance tended towards a better PFS than observation and was safe and most beneficial for patients in partial response and for unmutated IGHV cases. CLB-R represents a promising option for elderly CLL patients.

Dawn of the Delphinidans: New Remains of Kentriodon from the Lower Miocene of Italy Shed Light on the Early Radiation of the Most Diverse Extant Cetacean Clade.

Nowadays, the infraorder Delphinida (oceanic dolphins and kin) represents the most diverse extant clade of Cetacea, with delphinids alone accounting for more than 40% of the total number of living cetacean species. As for other cetacean groups, the Early Miocene represents a key interval for the evolutionary history of Delphinida, as it was during this time span that the delphinidans became broadly distributed worldwide, first and foremost with the widespread genus Kentriodon and closely related forms. Here, we report on a new odontocete find from Burdigalian (20.4-19.0 Ma) deposits of the Friulian-Venetian Basin of northeastern Italy, consisting of the partial cranium of a small delphinidan with associated ear bones (right periotic, stapes, malleus and tympanic bulla). Osteoanatomical considerations and comparisons allow us to assign the studied specimen to the genus Kentriodon. This is the first confirmed record of Kentriodon from Europe as well as from the whole proto-Mediterranean region. Stratigraphic and phylogenetic considerations suggest that our new specimen may represent the geologically oldest member of Kentriodon. The evolutionary success of Kentriodon may correlate with the emergence of narrow-band high-frequency echolocation as a possible strategy to escape acoustic detection by large marine predators such as the squalodontids. In addition, the relatively high encephalization quotient of Kentriodon spp. may have provided these early dolphins with some kind of competitive advantage over the coeval non-delphinidan odontocetes.

A phase II study of Givinostat in combination with hydroxycarbamide in patients with polycythaemia vera unresponsive to hydroxycarbamide monotherapy.

Givinostat, a histone-deacetylase inhibitor (HDACi), inhibits proliferation of cells bearing the JAK2 V617F mutation and has shown significant activity with good tolerability in patients with chronic myeloproliferative neoplasms (MPN). In this multicentre, open-label, phase II study, 44 patients with polycythaemia vera (PV), unresponsive to the maximum tolerated doses (MTD) of hydroxycarbamide (HC), were treated with Givinostat (50 or 100 mg/d) in combination with MTD of HC. The European LeukaemiaNet response criteria were used to assess the primary endpoint after 12 weeks of treatment. Complete or partial response was observed in 55% and 50% of patients receiving 50 or 100 mg of Givinostat, respectively. Control of pruritus was observed in 64% and 67% of patients in the 50 and 100 mg groups, respectively. The combination of Givinostat and HC was well tolerated: eight patients (18%) discontinued, four in each treatment arm; grade 3 adverse events were reported in one patient (4·5%) in each treatment arm. The combined use of Givinostat and HC was safe and clinically effective in HC-unresponsive PV patients.

AIDA 0493 protocol for newly diagnosed acute promyelocytic leukemia: very long-term results and role of maintenance.

All-trans-retinoic acid (ATRA) has greatly modified the prognosis of acute promyelocytic leukemia; however, the role of maintenance in patients in molecular complete remission after consolidation treatment is still debated. From July 1993 to May 2000, 807 genetically proven newly diagnosed acute promyelocytic leukemia patients received ATRA plus idarubicin as induction, followed by 3 intensive consolidation courses. Thereafter, patients reverse-transcribed polymerase chain reaction-negative for the PML-RARA fusion gene were randomized into 4 arms: oral 6-mercaptopurine and intramuscular methotrexate (arm 1); ATRA alone (arm 2); 3 months of arm1 alternating to 15 days of arm 2 (arm 3); and no further therapy (arm 4). Starting from February 1997, randomization was limited to ATRA-containing arms only (arms 2 and 3). Complete remission was achieved in 761 of 807 (94.3%) patients, and 681 completed the consolidation program. Of these, 664 (97.5%) were evaluated for the PML-RARA fusion gene, and 586 of 646 (90.7%) who tested reverse-transcribed polymerase chain reaction-negative were randomized to maintenance. The event-free survival estimate at 12 years was 68.9% (95% confidence interval, 66.4%-71.4%), and no differences in disease-free survival at 12 years were observed among the maintenance arms.

Dasatinib as first-line treatment for adult patients with Philadelphia chromosome-positive acute lymphoblastic leukemia.

Dasatinib is a potent BCR-ABL inhibitor effective in chronic myeloid leukemia and Ph(+) acute lymphoblastic leukemia (ALL) resistant/intolerant to imatinib. In the GIMEMA LAL1205 protocol, patients with newly diagnosed Ph(+) ALL older than 18 years (with no upper age limit) received dasatinib induction therapy for 84 days combined with steroids for the first 32 days and intrathecal chemotherapy. Postremission therapy was free. Fifty-three patients were evaluable (median age, 53.6 years). All patients achieved a complete hematologic remission (CHR), 49 (92.5%) at day 22. At this time point, 10 patients achieved a BCR-ABL reduction to < 10(-3). At 20 months, the overall survival was 69.2% and disease-free survival was 51.1%. A significant difference in DFS was observed between patients who showed at day 22 a decrease in BCR-ABL levels to < 10(-3) compared with patients who never reached these levels during induction. In multivariate analysis, BCR-ABL levels of < 10(-3) at day 85 correlated with disease-free survival. No deaths or relapses occurred during induction. Twenty-three patients relapsed after completing induction. A T315I mutation was detected in 12 of 17 relapsed cases. Treatment was well tolerated; only 4 patients discontinued therapy during the last phase of the induction when already in CHR. In adult Ph(+) ALL, induction treatment with dasatinib plus steroids is associated with a CHR in virtually all patients, irrespective of age, good compliance, no deaths, and a very rapid debulking of the neoplastic clone.

Biological activity of lenalidomide in myelodysplastic syndromes with del5q: results of gene expression profiling from a multicenter phase II study.

In vitro studies suggest that haploinsufficiency is involved in the pathogenesis of myelodysplastic syndromes (MDS). In patients with del5q cytogenetic abnormality, RPS-14 and microRNAs (miRNAs) play a major role. In a multicenter phase II single-arm trial with lenalidomide in anemic primary del5q MDS patients with low- or int-1 risk IPSS, biological changes from baseline were investigated. Gene expression profiling of selected genes was performed (TaqMan® Low Density Array Fluidic card, Applied Biosystems PRISM® 7900HT) and normalized against the expression of the 18S housekeeping gene from a pool of healthy subjects. Thirty-two patients were evaluated at baseline and after 3 and 6 months of treatment. RPS-14, miR-145, and miR-146 were downregulated at baseline and significantly increased during treatment. Nuclear factor kappa B, IL-6, interferon regulatory factor-1, IFNγ-R2, IL-2, and many genes in the apoptotic pathways (TNF, IL-1B, and IL-10) were upregulated at baseline and significantly downregulated during lenalidomide treatment, while forkhead box P3, FAS, IFNγ, IL-12A, and IL-12B were downregulated at baseline and progressively upregulated during treatment. The crucial role of aberrant immunological pathways and haploinsufficiency in the pathogenesis of del5q MDS is confirmed in the present patient setting. Our results indicate that lenalidomide may act through defined immunological pathways in this condition.

Quality of life in elderly patients with acute myeloid leukemia: patients may be more accurate than physicians.

BACKGROUND: The aim of this study was to evaluate changes in quality of life scores and their association with therapy and survival in unselected elderly patients with acute myeloid leukemia. DESIGN AND METHODS: From February 2003 to February 2007, 113 patients aged more than 60 years with de novo acute myeloid leukemia were enrolled in a prospective observational study. Two different quality of life instruments were employed: the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire - C30 (EORTC QLQ-C30) and a health-related quality of life questionnaire for patients with hematologic diseases (QOL-E). RESULTS: Forty-eight patients (42.4%) received intensive chemotherapy and 65 (57.6%) were given palliative treatments. Age greater than 70 years (P=0.007) and concomitant diseases (P=0.019) had a significant impact on treatment allocation. At diagnosis, general quality of life was affected [median QOL-E standardized score 54, interquartile range 46-70; median EORTC global score 50, interquartile range 41-66]. Most patients were given a good ECOG Performance Status (< 2), which did not correlate with the patients' perception of quality of life. At multivariate analysis, palliative approaches (P=0.016), age more than 70 years (P=0.013) and concomitant diseases (P=0.035) each had an independent negative impact on survival. In a multivariate model corrected for age, concomitant diseases and treatment option, survival was independently predicted by QOL-E functional (P=0.002) and EORTC QLQ-C30 physical function (P=0.030) scores. CONCLUSIONS: Quality of life could have an important role in elderly acute myeloid leukemia patients at diagnosis as a prognostic factor for survival and a potential factor for treatment decisions.

Waste not, want not: Report of a completely calcified C1-C2 juxtafacet cyst and literature review.

BACKGROUND: Calcified juxtafacet cysts in the cervical spine are extremely rate. Such symptomatic cysts commonly cause neck pain, radiculopathy, or even myelopathy. MR and CT studies typically document cord/ root compression. On occasion, some of these cysts will spontaneously regress, while many others may warrant surgical removal. CASE DESCRIPTION: A 70-year-old male presented with a 2-year history of a progressive tetraparesis. The preoperative MR/CT studies showed a C1-C2 left extradural mass occupying more than half of the spinal canal. On MR, it was homogeneously hypointense on both T1- and T2-weighted images, while the CT showed a calcified cyst. Intraoperative and histopathological findings documented a calcified cervical juxtafacet cyst (i.e. ganglion subtype) that was fully excised without sequelae. CONCLUSION: C1-C2 juxtafacet cervical cyst should be considered when a patient presents with myelopathy due to a calcified MR/CT documented paraspinal lesion contributing to significant cervical cord/root compression.

Iron chelation therapy associated with improvement of hematopoiesis in transfusion-dependent patients.

BACKGROUND: It is well known that iron overload may cause multiple organ failure. In chronically transfused patients, optimal iron chelation therapy is associated with reduced morbidity and mortality. Furthermore, chelation therapy has been associated with erythroid responses. STUDY DESIGN AND METHODS: Among chronically transfused adults affected by myeloproliferative neoplasms and treated with iron chelators, two case reports are described. CASE REPORT: A male adult patient with myelodysplastic syndrome (MDS) and a female adult with aplastic anemia (AA), both transfusion-dependent, were treated with deferasirox, an oral iron chelator. RESULTS: A significant reduction in transfusion requirement was observed and was dependent on chelation therapy. The patient affected by AA also experienced a significant increase in hemoglobin levels. Minimal doses of deferasirox maintained the erythroid responses. Many mechanisms of action of the drug on erythropoiesis have been postulated. The early erythroid response seems to be independent of the removal of iron from deposits, per se, since the reduction of ferritin levels (a surrogate marker of iron deposits) below threshold levels occurs as a later event. CONCLUSION: Although there are few reports on erythroid responses in patients undergoing iron chelation therapy, they may give new insights in the pathogenesis of MDS and other myeloproliferative neoplasms. AA may benefit in terms of erythroid response. The findings in these cases underline the clinical importance of treating patients with iron overload. A survival benefit of chelation in patients with myeloproliferative neoplasms is still to be confirmed.

Changes in RPS14 expression levels during lenalidomide treatment in Low- and Intermediate-1-risk myelodysplastic syndromes with chromosome 5q deletion.

BACKGROUND: Haploinsufficiency of the ribosomal protein S14 RPS14 gene, located in the common deleted region of chromosome 5q, is a potential causal factor of 5q- syndrome. Lenalidomide elicits high response rates and morphological improvements in myelodysplastic syndrome (MDS) patients with chromosome 5q deletion [del(5q)]. METHODS: To further evaluate the role of RPS14, its transcription was tested in bone marrow cells from 17 patients with International Prognostic Scoring System defined Low- or Intermediate-1-risk MDS with del(5q) as a single or additional cytogenetic abnormality receiving treatment with lenalidomide. RESULTS: After 12 wk of lenalidomide treatment, erythroid responses were observed in all cases with an increase in hemoglobin levels of 2.7 +/- 2.5 g/dL (up to a mean 11.8 +/- 1.9 g/dL; P = 0.001). Before treatment, RPS14 expression levels were under-expressed in 15 patients with respect to normal controls. After 12 wk of lenalidomide treatment, all patients had an erythroid response. There was a significant increase in median RPS14 expression from baseline 0.01 (IQR 0.05-0.31) to 12 wk 204.71-fold (2.86-446.32; P < 0.0001). CONCLUSIONS: These observations in the patient setting support the importance of RPS14 in the pathogenesis of MDS with del(5q).

Health-related quality of life, symptom burden, and comorbidity in long-term survivors of acute promyelocytic leukemia.

The objective of this study was to investigate health-related quality of life (HRQOL), symptom burden, and comorbidity profile in long-term acute promyelocytic leukemia (APL) survivors treated with standard chemotherapy. Overall, 307 long-term APL survivors were invited to participate. HRQOL was assessed with the Medical Outcomes Study 36-Item Short-Form Health Survey (SF-36) and compared with that of age and sex-matched controls from the general population. Symptom burden was assessed with the MD Anderson Symptom Inventory (MDASI) questionnaire and comorbidity profile was also investigated. Median follow-up time since diagnosis was 14.3 years (interquartile range: 11.1-16.9 years). APL survivors had a statistically and clinically meaningful worse score for the role physical scale of the SF-36 (-9.5; 95% CI, -15.7 to -3.2, P = 0.003) than their peers in the general population. Fatigue was reported as moderate to severe by 29% of patients and 84.4% reported at least one comorbidity. Prevalence of comorbidity in APL survivors was higher than that reported by the general population. Also, marked variations were found in the HRQOL profile by number of comorbidities. Even many years after treatment ends, APL survivors treated with standard chemotherapy do not fully recover as they report HRQOL limitations and a substantial burden of symptoms.

Rapid malignant progression of an intraparenchymal choroid plexus papillomas.

BACKGROUND: Choroid plexus tumors (CPTs) are rare neoplasms accounting for only 0.3-0.6% of all brain tumors in adults and 2-5% in children. The World Health Organization (WHO) classification describes three histological grades: grade I is choroid plexus papilloma (CPP), grade II is atypical papilloma, and grade III is the malignant form of carcinoma. In adults, CPTs rarely have a supratentorial localization. CASE DESCRIPTION: Here we report a very rare case of an intraparenchymal parietal CPP with a rapid histological transition from grade I to grade III WHO in a 67-year-old man, in <7 months. CONCLUSION: Because of the rarity of these oncotypes, descriptions of each new case are useful, mostly to consider this diagnostic entity in extraventricular brain tumors of adults, despite an unusual location.

Use of Common Inflammatory Markers in the Long-Term Screening of Total Hip Arthroprosthesis Infections: Our Experience.

Orthopedic implants have become essential components of modern medicine. The risk of infection of total hip arthroplasty (THA) is 1.5%-2%. Are the C-reactive protein (CRP), the erythrocyte sedimentation rate (ESR), and procalcitonin (PCT) good markers for THA infection screenings? From February 2009 to December 2012 at our Department of Orthopedics and Traumatology, 1248 patients were treated with THA. No prosthesis was cemented. All patients received antibiotic prophylaxis. All patients were discharged approximately 7.4 days after surgery with this clinical and radiographic follow-up program at 15 days and 1, 3, 6, 12, 24, and 36 months after surgery. Blood samples to determine ESR, CRP, and PCT values were taken at 1 hour before surgery and 15 days and 1, 3, 6, 12, 24, and 36 months after surgery. During follow-ups there were 22 cases of THA infections; according the Widmer classification, infections are hematogenous ones in 16 cases, late chronic ones in 5 cases, and early postoperative ones in 1 case. In all cases the three markers were considered positive; in 6 cases there were no radiological signs of septic loosening. ESR, CRP, and PCT proved to have a greater diagnostic accuracy than X-rays in predicting late chronic and early postoperative infections. These markers are valuable support for the surgeon in monitoring the prosthetic implant lifespan.

The biological characteristics of CD34+ CD2+ adult acute promyelocytic leukemia and the CD34 CD2 hypergranular (M3) and microgranular (M3v) phenotypes.

BACKGROUND AND OBJECTIVES: Acute promyelocytic leukemia (APL) is characterized by leukemic cells blocked at the promyelocytic stage of granulocytic differentiation. To date, it is still not clear whether CD34 expression identifies a subset of APL patients with peculiar characteristics. We, therefore, conducted a detailed analysis of CD34 expression at diagnosis in 136 adults with de novo APL. DESIGN AND METHODS: We investigated 136 newly diagnosed APL patients from four Italian Institutions. All 136 cases were tested for CD34 and CD2 expression: 124 (91%) cases were classified as hypergranular (M3) and 12 (9%) as the hyporgranular M3 variant (M3v). The parameters considered were white blood cell (WBC) and platelet counts, hemoglobin levels, percentage of peripheral blood leukemic promyelocytes (PBLP), CD15, CD56 and HLA-DR expression, and the PML/RARalpha isoform, to assess their relationship with CD34 and CD2 expression. RESULTS: CD34 expression was associated with the M3v subtype and higher proportion of HLA-DR+ and CD2+ cases. Moreover, compared with CD34- APL patients, CD34+ APL patients had a significantly higher percentage of PBLP at presentation, were more frequently female and had a higher proportion of bcr3 expression. Among the 136 APL cases, 24 (17.6%) and 80 (58.8%) were identified as CD34+CD2+ and CD34-CD2-, respectively. The two groups showed statistically significant differences in terms of M3vfrequency, WBC and platelet counts, percentage of PBLP, and bcr3 expression. Moreover, the CD34+CD2+ group showed a higher proportion of CD34+ and bcr3 isoforms compared to the M3v cases. There were no differences between the two groups in terms of complete remission, overall survival and disease-free survival. INTERPRETATION AND CONCLUSIONS: Our findings suggest that immunophenotypic analysis can distinguish a subset of APL patients with different biological characteristics.

Incidence of second neoplasia in patients with B-cell chronic lymphocytic leukemia treated with chlorambucil maintenance chemotherapy.

The aim of this retrospective study was to examine the impact of prolonged chlorambucil (CLB) therapy on the development of second neoplasia (SN) in 389 patients with B-CLL, comparing untreated cases with those receiving CLB as induction plus maintenance therapy. Fifty-nine SN cases were observed (15.1%) at a median follow-up of 79 months. SN occurrence was significantly related to Binet stage. No difference was detected between untreated and CLB treated cases neither in terms of SN incidence (12.2% vs 18.1%) nor in the median follow-up (81 vs 79.1 months). Moreover, SN free survival was not different between these two groups. Four out of 13 CLB treated patients (30.8%) developed s-MDS after a subsequent treatment with fludarabine plus cyclophosphamide (F + C). In conclusion, SN development is dependent on the length of follow-up rather than on therapy duration. F + C should be administered with caution after prolonged CLB therapy.

Hemoglobin level threshold for cardiac remodeling and quality of life in myelodysplastic syndrome.

Treatment of myelodysplastic syndrome (MDS) with epoietin is costly. However, cardiac morbidity associated with anemia has not been investigated in MDS. We studied this aspect in 39 patients. Echocardiography detected cardiac remodeling in 11 of 12 transfusion-dependent versus 13 of 27 transfusion-free patients (P=0.017). Hemoglobin independently indicated cardiac hypertrophy (P=0.004); each unit increase predicted a 49% reduction in the risk of remodeling confirmed by the area under the ROC curve (0.84, P<0.0001). At Hb 10.7 g/dL, sensitivity was 96% and specificity 64%. Below this level quality of life was poorer. Our results suggest early treatment, to be confirmed by future trials.

Prognostic role of minimal residual disease in multiple myeloma patients after non-myeloablative allogeneic transplantation.

This study evaluates the prognostic value of molecular monitoring of minimal residual disease (MRD) in 20 patients with multiple myeloma (MM) following autologous (peripheral blood stem cell transplantation, PBSCT) and non-myeloablative allogeneic (NMT) transplant. All patients completed their program, with a treatment-related mortality (TRM) of 20% and a 2-year progression-free survival (PFS) of 51%. After PBSCT, only 3 patients (15%) achieved PCR-negativity, versus 12 (60%) after NMT. The eradication of MRD had a favorable impact on 2-year OS. In fact, 76% of patients with no detectable MRD was still alive versus 34% of persistently IgH-positive cases (p=0.03). PCR status did not correlate with chimerism percentage: Seventy-five percent of patients achieved full donor chimerism, which was more frequently observed in cases presenting cGHVD (p=0.01). These data sustain the relevant role of molecular monitoring in MM patients undergoing NMT. MRD monitoring would assist physicians in making additional therapeutic decisions to better control this hematological malignancy.

Differences in transplant-related complications between hematologic malignancies and solid tumors receiving high-dose chemotherapy and autologous peripheral blood stem cell transplantation.

Multiple factors contribute to transplant-related complications after high-dose chemotherapy followed by autologous peripheral blood stem cell transplantation, including conditioning regimens, number of infused stem cells and clinical characteristics of patient at transplant. We compared the transplant-related complications of 141 patients affected with hematological malignancies with those of 109 patients with solid tumors. The total number of peripheral blood stem cell transplantations performed was 339. High-dose chemotherapy mainly consisted of melphalan-, busulphan- or thiotepa-based regimens. Despite the equal number of infused CD34+ cells, patients with a hematological malignancy showed a slower absolute neutrophil count (days to neutrophils > 0.5 x 10(9)/L, 10.6 +/- 3.6 for hematological malignancies versus 9.1 +/- 1.2 for solid tumors, P < 0.0001) and platelet recovery (days to platelets > 20 x 10(9)/L, 16.4 +/- 9.8 for hematological malignancies versus 12.3 +/- 4.1 for solid tumors, P < 0.0001) than patients with a solid tumor. A significantly higher requirement of red blood cell (3.3 +/- 4.1 versus 2.0 +/- 1.9, P < 0.0029) and platelet units (7.5 +/- 10.4 versus 4.2 +/- 3.4, P < 0.0001) was observed for hematological malignancies than for solid tumors. Five graft failures were documented exclusively in patients with a hematological malignancy. Moreover, such patients displayed a longer duration of mucositis (P < 0.0028) and hospital stay (P < 0.0001), but no difference was observed in terms of febrile episodes. Transplant-related mortality was similar between the two groups. In conclusion, patients with a hematological malignancy overall have more complications than those with a solid tumor.

Serum C-reactive protein and procalcitonin kinetics in patients undergoing elective total hip arthroplasty.

BACKGROUND: The sensitivity and the specificity of different methods to detect periprosthetic infection have been questioned. The current study aimed to investigate the kinetics of C-reactive protein (CRP) and procalcitonin (PCT) in patients undergoing uncomplicated elective total hip arthroplasty (THA), to provide a better interpretation of their levels in noninfectious inflammatory reaction. METHODS: A total of 51 patients were included. Serum CRP and PCT concentrations were obtained before surgery, on the 1st, 3rd, and 7th postoperative days and after discharge on the 14th and 30th days and at 2 years. RESULTS: Both markers were confirmed to increase after surgery. The serum CRP showed a marked increase on the 3rd postoperative day while the peak of serum PCT was earlier, even if much lower, on the first day. Then, they declined slowly approaching the baseline values by the second postoperative week. PCT mean values never exceed concentrations typically related to bacterial infections. CONCLUSIONS: CRP is very sensitive to inflammation. It could be the routine screening test in the follow-up of THA orthopaedic patients, but it should be complemented by PCT when there is the clinical suspicion of periprosthetic infection.

Fludarabine plus alemtuzumab (FA) front-line treatment in young patients with chronic lymphocytic leukemia (CLL) and an adverse biologic profile.

In 45, ≤ 60 years old patients with CLL and an adverse biologic profile, a front-line treatment with Fludarabine and Campath (Alemtuzumab(®)) was given. The overall response rate was 75.5%, the complete response rate (CR) 24.4% with the lowest CR rates, 16.7% and 8.3%, in 11q and 17p deleted cases. The 3-year progression-free survival (PFS) and overall survival were 42.5% and 79.9%, respectively. PFS was significantly influenced by CLL duration, beta2-microglobulin, and improved by post-remissional stem cell transplantation. Front-line fludarabine and alemtuzumab showed a manageable safety profile and evidence of a benefit in a small series of CLL patients with adverse biologic features.