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The occurrence of an acute myeloid leukemia (AML) relapse is generally observed within 2–3 years after complete remission (CR) and affects the overall survival rate of these patients [1]. Few studi...

Acute lymphoblastic leukemia (ALL) is the most common childhood cancer with the majority of cases being of B lineage [1]. B-cell precursor ALL (BCP-ALL) is a heterogeneous disease in which risk ass...

Clofarabine (CLO) and cyclophosphamide (CY) combinations were tested in late stage refractory/relapsed (R/R) acute lymphoblastic leukemia (ALL) with disappointing results and high-grade toxicity. We designed a sequential 5-day combination of CLO 40 mg/m

Since 2000, an adapted LMB 96 protocol was implemented at the Children-Welfare-Teaching-Hospital in Baghdad for the treatment of childhood B-cell non-Hodgkin lymphoma. The first experience (2000-2005) demonstrated efficacy and feasibility of this protocol in Iraq. In 2006, further adjustments were made in an attempt to reduce therapy-related toxicities. The outcome of the second cohort of 190 children (2006-2010) and the comparison with the previous study are hereby reported. Out of the 180 treated patients, 120 achieved a complete response; during treatment 51 died and 9 abandoned. The 60-month overall survival (OS) and event-free survival (EFS) were 64.7 and 56.3%, respectively. No differences were observed in the 24-month OS and EFS between the 2000-2005 and 2006-2010 cohorts (66.3% vs. 65.1%; p = .89 and 53.3% vs. 57.3%; p = .28, respectively). Therapeutic group-B in the second cohort showed better outcome, although not significant, compared to the first one (EFS 62.9% vs. 53.8%; p = .088). Therapy-related mortality remained high.

Discontinuation of tyrosine kinase inhibitors (TKIs) in chronic phase chronic myeloid leukemia (CP-CML) patients has become a reality. Treatment-free remission (TFR) defines the rate of success aft...

During the past three decades, allogeneic stem cell transplant (allo-SCT) has been considered the standard of care for adult patients with high-risk acute lymphoblastic leukemia (ALL) and, given th...

Autoimmune hemolytic anemia (AIHA) is one of the most common disease-specific complications of chronic lymphocytic leukemia (CLL), occurring in 3–10% of patients, with a higher incidence in advance...

Late relapse, defined as occurring 3 or more years from the achievement of complete remission (CR) according to the definition of long-term survival published by Eastern Cooperative Oncology Group ...

In chronic lymphocytic leukemia, NOTCH1, SF3B1, BIRC3 and TP53 disruptions are recurrent and affect survival. To define their incidence and clinical impact in patients undergoing first-line treatment, we evaluated 163 cases enrolled in the GIMEMA (Gruppo Italiano Malattie EMatologiche dell'Adulto) LLC0405 protocol (fludarabine plus alemtuzumab or fludarabine plus cyclophosphamide), for young patients, or in the ML21445 protocol (chlorambucil plus rituximab), for elderly patients. NOTCH1, SF3B1, BIRC3 and TP53 disruptions were detected in 15.9%, 12.2%, 8.6% and 10.4% of cases. NOTCH1 mutations correlated with a shorter treatment-free interval (p = 0.058), an unmutated immunoglobulin heavy variable gene (IGHV) status (p0.0001), CD38 and ZAP-70 expression (p = 0.0025 and 0.026, respectively) and trisomy 12 (p = 0.0028), SF3B1 mutations with an unmutated IGHV status (p = 0.02), and BIRC3 disruptions with an unmutated IGHV configuration (p = 0.01) and 11q deletion (p0.0001). NOTCH1 and SF3B1 did not appear to impact on overall response, while an inferior response was observed for BIRC3- and TP53-disrupted cases in the LLC0405 and ML21445 protocols, respectively. Progression-free survival, evaluable in the LLC0405 protocol - not affected by NOTCH1, SF3B1 and TP53 - appeared inferior for BIRC3 disruption. NOTCH1 and SF3B1 mutations may be overcome by aggressive regimens, while BIRC3 might impact on outcome also in intensive regimens.

Monoclonal B-cell lymphocytosis (MBL) is a recently defined medical condition that displays biological similarities to chronic lymphocytic leukemia (CLL), the most common subtype of adult leukemia in the Western world. MBL may be diagnosed in individuals with a normal lymphocyte count via a screening assay (screening MBL) or through the clinical evaluation of lymphocytosis (clinical MBL). Clinical MBL, which resembles CLL with a good prognosis, has attracted considerable interest because of its clinical and biological implications. The biological profile of clinical MBL appears indistinguishable from that of CLL for a large variety of markers. Differential diagnosis between clinical MBL and CLL is mainly based on peripheral blood B-cell counts. The 2008 International Workshop on Chronic Lymphocytic Leukemia (IWCLL) criteria changed the definition of CLL to a B-cell count ≥ 5.0 × 10(9)/L to eliminate overlap between CLL and MBL. However, this cut-off is arbitrary, and recent studies suggest that a B-cell count of 10.0-11.0 × 10(9)/L may represent the threshold that best predicts time to first treatment. After a diagnosis of clinical MBL, patients should be educated about appropriate monitoring and follow-up keeping in mind that, with time and counseling, most patients will understand that clinical MBL and CLL represent a continuum.

Monoclonal antibody (MoAb)-based therapies have opened innovative treatment avenues that have impacted on the management of patients with both neoplastic and non-neoplastic hematological diseases. The aim of our study was to evaluate in a large series of cases of acute lymphoblastic leukemia (ALL) the expression of specific antigens, CD19, CD20, CD22, and CD33, for which MoAbs are available for clinical use. For each antigen, evaluation was based on the percentage of positive leukemic cells and the degree of antigen expression by mean fluorescence intensity (MFI) and antibody binding capacity (ABC) that were correlated with age, immunophenotype, and presence/absence of particular molecular markers. We can document that some of the analyzed antigens showed a degree of expression related to the B-cell maturation profile, and that the antigen expression intensity appeared to vary according to the presence of specific genetic markers. These findings suggest that the possible clinical use of a given MoAb in patients with ALL should take into account both the maturation profile of the leukemic cells and the presence of a given molecular transcript. Only clinical studies will conclusively demonstrate whether the differences in antigenic expression truly correlate with the different therapeutic efficacies of the various clinical grade MoAbs.

The BEACOPP regimen is a consolidated first-line treatment regimen for advanced stage Hodgkin lymphoma (HL), while few data are available on the efficacy of this regimen in advanced disease. About 50% of patients with HL relapsed after or refractory to first-line therapy achieve a durable response after peripheral blood stem cell transplantation (PBSCT). Patients relapsing after a PBSCT (performed as second line therapy) have a very poor prognosis. We evaluated the efficacy of BEACOPP in two settings: patients refractory or in relapse after first-line therapy (Group A) and patients relapsing after a PBSCT (Group B). Twenty-three patients with HL, admitted between February 2003 and April 2007, were retrospectively studied: 10 patients in Group A and 13 in Group B. Group A: Nine complete remissions (CR) and one partial remission (PR) were achieved following BEACOPP treatment. After a median follow-up of 32 months, one patient has died due to secondary leukemia, while the other eight are alive, five (50%) in second CR, three in third CR after PBSCT and one with disease. Group B: Eight of the 13 patients (62%) obtained a CR, one patient a PR, two were refractory and two have died of toxicity. To date, eight patients (62%) are alive, four (31%) still in CR. All patients experienced hematologic toxicity (WHO 3-4) with two deaths due to septic shock. These results show that BEACOPP is an effective regimen for both refractory/relapsed patients with HL after first-line treatment (Group A) and for patients relapsing after a PBSCT (Group B) with a 3-year probability of overall survival, progression-free survival, and cumulative incidence of relapse of 90, 50, and 33.3% in Group A, and 61, 31, and 37.5% in Group B, respectively.

Patients with advanced hematological malignancies may experience many troublesome hemorrhagic complications requiring hospitalisation during a palliative home care (HC) program. We report on the feasibility of the management of bleeding at home in patients with haematological malignancies admitted in a domiciliary HC program. The occurrence of a major hemorrhage episode (>1 WHO grade) was registered among 469 patients with hematological malignancies in the terminal phase of their disease followed at home. Number, sites, domiciliary treatment (local hemostatic measures, platelet units, hemostatic drugs, packed red blood cells) and outcome of hemorrhagic complications were evaluated. Out of 469 patients, 123 (26%) experienced a bleeding complication; the overall number of hemorrhagic episodes was 232 (49%) with a median number of 2 episodes per patient. Patients with a platelet count lower than 20 x 10(9)/L (P < 0.00005) or with a diagnosis of acute leukemia or in blast crisis of myeloprolypherative disorders (P < 0.00005) showed a significant higher incidence of hemorrhages than other patients. Resolution of bleeding at home was obtained in 206 (88%) of the 232 episodes; platelet units were transfused at home in 188 (81%) cases. Bleeding was the cause of hospitalisation in four cases. Death occurred in 447 of 469 patients: in 26 of them (6%), it was caused by bleeding complications (11 brain hemorrhage, 2 hematemesis, 3 hemoptysis and 10 melena). In this group of patients, bleeding was a relevant clinical problem However, by implementing a domiciliary palliative care program, home management of hemorrhages proved to be a safe and effective choice.

This study hereby reports the case of a 19-year old boy with a gamma-delta hepatosplenic T-cell lymphoma (HSTCL). Initial therapy consisted of four cycles of the IEV (Ifosphamide, Epirubicin and Etoposide) scheme. Further treatment strategy was then adapted according to minimal residual disease monitoring by immunophenotypic and T-cell receptor gamma chain gene evaluation. The patient remains in complete clinical, immunological and molecular remission and in good clinical conditions 48 months after diagnosis and 40 months after stopping therapy.

Plasma cell leukemia (PCL) represents the most advanced stage of multiple myeloma (MM) with the neoplastic cells circulating in the peripheral blood. Its diagnosis requires an absolute peripheral b...

Two cell lines were originated from the peripheral blood (PB-LAM) and bone-marrow (BM-LAM) of a patient with Burkitt-type acute lymphoblastic leukemia and AIDS. 26 and 7 clones were isolated from PB-LAM and BM-LAM respectively by limiting dilution. All of these had surface IgM lambda and the CD10 marker with low to absent CD23, CD30, CD39 and surface adhesion molecules. Furthermore, they shared the same chromosomal abnormalities (trisomy 7 and t(8;14) translocation) and the same rearrangements of immunoglobulin L and H chain and of c-myc gene loci. These features are those most frequently found in Burkitt's lymphoma (BL) cells and were different from those of the parental cell lines, which, besides cells identical to those of the malignant clones, also contained normal lymphoblastoid cells. Therefore, the cloning procedure used selected for the growth of cells with malignant features. EBV latent antigens were detected in all clones by Western blotting and their pattern of expression resembled that usually observed in BL cells. All the clones were positive for the EBV genome by Southern blotting and had monomorphic EBV-fused termini as determined by using cDNA probes specific for sequences at either end of the viral genome. However, the clones derived from PB-LAM had EBV fused termini of a different size from that of the clones derived from BM-LAM. The presence of different EBV-fused termini in otherwise monoclonal malignant cells indicate that EBV infection was possibly a late event in lymphomagenesis following rearrangement of the c-myc and the Ig gene loci.

We hereby here the successful use of a combined therapeutic approach with alpha 2b Interferon (IFN) and Chlorambucil in the management of previously treated B-cell chronic lymphocytic leukemia (B-CLL). The two patients under study had been managed with repeated and frequent cycles of Chlorambucil. Rather than with more toxic multidrug regimens, the hematological picture was controlled with 3 MU of IFN every three-five days and 5 mg of Chlorambucil every two-five days. Using such an approach, which is feasible on an out-patients basis and devoid of significant side effects, a consistent control of the WBC count was achieved for 32 and 16 months, respectively.

In fourteen patients with hairy cell leukemia (HCL) the configuration of the immunoglobulin (Ig) heavy chain genes was used as a marker of clonality, to monitor the response of the neoplastic population to treatment with alpha-interferon (a-IFN). In agreement with the morphological, hematological and immunological data, twelve of them showed, after a variable length of therapy, a complete disappearance of rearranged bands in peripheral blood cells. In one patient, who was treated less intensively, the molecularly-defined neoplastic population was still present on two consecutive determinations, whilst in the last patient persistence of disease was repeatedly documented despite prolonged A-IFN treatment. Three further cases were analyzed sequentially: in two, no rearranged bands could be found at repeated determinations; the third, who was in complete remission whilst on 3 × 10(6) U of α-IFN every other day, showed recurrence of disease nine months later when on a maintenance protocol with 3 × 10(6) U/weekly. Nine bone marrow specimens were also analyzed following treatment with α-IFN. In four a monoclonally rearranged band could still be detected, while in another four, reversal of fibrosis and hemopoietic recovery wits coupled with the absence of a molecularly recognizable neoplastic clone. In the last (case, persistence of disease paralleled the findings in the peripheral blood cells. These data indicate that α-IFPJ is capable of producing a specific cytolytic effect on the leukemic population in HCL, which in some cases may lead to complete clonal remissions. Analysis at the DNA level may represent a valuable tool towards monitoring the clinical course of HCL patients and for optimal individual therapeutic scheduling.