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To present the initial assessment of psychosocial adaptation among Greek parents whose children were newly diagnosed with cancer amidst the turmoil of an ongoing financial crisis.This prospective observational study used a quantitative approach.Sixty-one parents of children with cancer treated at a large urban tertiary-care children's hospital were prospectively recruited to participate in our study during the first week of their child's diagnosis (2013-2016).The parents were asked to complete the psychosocial assessment tool (PAT 2.0), Zung Depression Scale, State-Trait Anxiety Inventory, Hospital Anxiety and Depression Scale, and World Health Organization Quality of Life-Bref Instrument; Moreover, three female healthcare providers (the physician oncologist, the head nurse and a senior nurse) completed the relevant PAT 2.0 -Staff Perceptions questionnaire the results of which were then compared to those of the child's parent.The majority of parents had PAT 2.0 scores indicative of increased psychosocial risk :54% were stratified into the "Targeted" (moderate risk) and 15% into the "Clinical" (highest risk) categories, whereas healthcare providers underestimated psychosocial risk in 57%-59% of the cases. The subscales that most contributed to the increased scores were Parental Stress Reaction, Family Structure and Resources, and Family Social Support. The PAT 2.0 had statistically significant correlations with most of the anxiety and depression scales, with Zung having the strongest correlation (r-value: +0.5,The parents of children newly diagnosed with cancer in Greece are at increased risk for developing anxiety and depression in the years of financial recession in Greece compared to general population.Parental stress reaction to diagnosis as well as lack of family resources and social support may contribute to this difference. Screening for psychosocial risk factors is essential for the early identification of these families and for the optimal utilization of the limited available resources in times of economic hardship.

Opposing acute lymphoblastic leukemia, sparse data about AYAs with acute myeloid leukemia (AML) is available. Overall, 125 AYAs (age 10-35 years) treated during the last two decades were evaluated and compared to 385 older patients. CBF leukemia was more frequent in AYAs (21.6% vs. 8%

Bone marrow failure (BMF) syndromes are a group of various hematological diseases with cytopenia as a main common characteristic. Given their rarity and continuous progress in the field, we aim to provide data considering the efficiency and safety of the therapeutic methods, focusing on the treatment of aplastic anemia(AA) and paroxysmal nocturnal hemoglobinuria (PNH). We enrolled consecutive patients diagnosed with BMF in two referral centers of Northern Greece from 2008 to 2020. We studied 43 patients with AA (37 adults and 6 children/adolescents) and 6 with classical PNH. Regarding classical PNH, 4 patients have received eculizumab treatment with 1/4 presenting extravascular hemolysis. Among 43 patients with aplastic anemia, PNH clones were detected in 11. Regarding patients that did not receive alloHCT (n=15), 14/15 were treated with ATG and cyclosporine as first line, with the addition of eltrombopag in patients treated after its approval (n=9). With a median follow-up of 16.7 (1.8-56.2) months from diagnosis, 12/14 (85.7%) are alive (4-year OS: 85.1%). AlloHCT was performed in 28 patients. Five patients developed TA-TMA which did not resolve in 3/5 (all with a pre-transplant PNH clone). With the follow-up among survivors reaching 86.3 (6.3-262.4) months, 10-year OS was 56.9%, independently associated with PNH clones after adjusting for age (p=0.024). In conclusion, our real-world experience confirms that novel treatments are changing the field of BMF syndromes. Nevertheless, there is still an unmet need to personalize algorithms in this field.

Therapy related acute myeloid leukemia (tAML) and secondary AML after an antecedent hematologic disorder (sAML-AHD) are often addressed together, blurring any clinical and prognostic differences. Among 516 AML patients, we compared characteristics and outcomes of 149 patients with “sAML” (sAML-AHD: 104, tAML: 45), uniformly and intensively treated during the last 2 decades at 1 center. Clinical outcomes of the whole “sAML” cohort were significantly inferior compared to de novo AML and in both intermediate and poor cytogenetic risk groups. Adverse karyotype had no effect on survival in tAML, while it was a negative predictor in sAML-AHD. Both groups showed similarly dismal outcome, with low complete remission rates (CR 44% vs. 41%) and median overall survival (OS 7 vs. 10.5 months). Allogeneic hematopoietic cell transplantation (alloHCT) recipients in CR1 had superior median OS (24 vs. 8 months). By multivariate analysis, alloHCT was an independent predictor of outcome, while karyotype was for sAML-AHD only. In conclusion, both “sAML” groups have inferior outcomes after chemotherapy, with adverse karyotype affecting primarily sAML-AHD. Until new treatment approaches are available, only alloHCT offers a survival advantage.

We have previously shown an advantage of a myeloablative conditioning regimen with reduced toxicity (Fludarabine 150 mg/m2, Treosulfan 42 g/m2, FluTreo) compared to a reduced-intensity regimen. We aimed to determine long-term safety and efficacy of FluTreo. We prospectively studied consecutive patients who received FluTreo in our center (2014-2019) on the basis of age (≥50 years), hematopoietic cell transplantation comorbidity index (HCT-CI) ≥2, or both. FluTreo recipients were then compared to a historical control group. We studied 68 FluTreo recipients, with a median age of 58.5 years and HCT-CI of 3. We calculated cumulative incidence (CI) of acute (grade 2-4) and moderate/severe chronic graft-versus-host disease (GVHD) (29.9% and 25%, respectively). The 3-year CI of treatment-related mortality was 19.1%, associated only with acute GVHD (P

Targeted therapies are on the market for the past five years and recently pembrolizumab was approved as first line treatment for patients with PD-L1 >50%. We present three cases of patients which had epidermal growth factor receptor positive expression and programmed death-ligand 1 (PD-L1), PD-L1 >50% overexpression.

Guidelines for the treatment of non-small cell lung cancer adenocarcinoma positive in epidermal growth factor mutations indicate tyrosine kinase inhibitors. There are currently three tyrosine kinase inhibitors that can be used as first line treatment: gefitinib, erlotinib and afatinib. Regarding erlotinib and afatinib dosage can be modified in the case of severe adverse effects. In the case of disease relapse investigation for T790M mutation has to be made either with re-biopsy or liquid biopsy and osimertinib has to be administered when T790M is diagnosed. Based on a case series we indicate which is the best approach for T790M mutation.

In the past decade novel agents are on the market for non-small cell lung cancer adenocarcinoma based on pharmacogenomics. The epidermal growth factor receptor mutation, anaplastic lymphoma kinase and programmed death-ligand 1 investigation is necessary in the everyday clinical practice for the oncologic patient. Immunotherapy is nowadays the novel therapy for advanced stage non-small cell lung cancer with two agents nivolumab and pembrolizumab. In the current case series we will present adverse effects from our centers and comment on the treatment and follow-up of the patients.

Background: Secondary or treatment-related acute myeloid leukemia (sAML) is associated with poor outcomes. Although allogeneic hematopoietic cell transplantation (alloHCT) is the treatment of choice, patient eligibility criteria and optimal conditioning regimen remain under study. We have previously shown an advantage of a myeloablative conditioning regimen with reduced toxicity (Fludarabine 150mg/m2, Treosulfan 42g/m2, FluTreo) compared to a reduced intensity regimen. However, the long-term effects of this regimen remain unknown, especially in comparison to patients not receiving alloHCT. Aims: We hypothesized that patients transplanted with FluTreo would have a long-term survival advantage over other treatment alternatives. Methods: We retrospectively studied consecutive patients treated for sAML in our center over the last two decades (1998-2018). Exclusion criteria were: age>70 years, ECOG performance status≥3 at presentation, induction regimens≤2, and autologous or haploidentical HCT because these were performed in individual patients. Since 2013, we have introduced FluTreo for patients with a suitable donor that would have been previously eligible only for reduced intensity conditioning/RIC. The following factors were studied in the whole cohort: age, type of disease (treatment-related or post myelodysplastic syndrome/MDS), previous intensive chemotherapy cycles, cytogenetic risk, overall (OS) and disease-free survival (DFS). In transplant recipients, we also recorded HCT-comorbidity index/CI score, cumulative incidence (CI) of graft-versus-host disease (GVHD), and treatment-related mortality (TRM). Follow-up was calculated from diagnosis in the whole cohort; and from date of transplant in the sub-group analysis of transplant recipients. Results: We studied 19 FluTreo recipients compared to 46 recipients of other conditioning regimens (38 myeloablative and 8 RIC), and 52 patients treated only with chemotherapy. Complete remission (CR) had been achieved in all FluTreo recipients before HCT, compared to 53% of other transplants, and 44% of chemotherapy only patients (p Within transplanted patients, there was no significant difference in GVHD, relapse and TRM between FluTreo and other transplants. Within the FluTreo group, acceptable rates of CI in severe acute and extensive chronic GVHD were observed (15.2% and 18.4%, respectively). Similarly, 4-year CI of TRM reached 30.4%, despite a median HCT-CI of 3 (0-7), age of 59 (51-67) years, 4 lines of treatment (3-6), and a majority of matched unrelated donors (13/19). Conclusion: Our real-world study confirms that alloHCT with FluTreo expands the transplant population with similar safety and efficacy to previous transplant modalities in sAML patients. Achievement of CR remains a major predictor of OS in these patients. The choice of alloHCT in this unique patient population of a rather older age and comorbidity index needs to be revisited. Figure 1 Disclosures Gavriilaki: Omeros Pharmaceuticals: Consultancy.

Recent evidence suggests that complex karyotype (CK) defined by the presence of =3 chromosomal aberrations (structural and/or numerical) identified by chromosome banding analysis (CBA) may be relevant for treatment decision-making in chronic lymphocytic leukemia (CLL). However, many challenges towards routine clinical application of CBA remain. In a retrospective study of 5290 patients with available CBA data, we explored both clinicobiological associations and the clinical impact of CK in CLL. We found that patients with =5 abnormalities, defined as high-CK, exhibit uniformly dismal clinical outcome, independently of clinical stage, TP53 aberrations (deletion of chromosome 17p and or TP53 mutations, TP53abs) and the expression of somatically hypermutated (M-CLL) or unmutated (U-CLL) immunoglobulin heavy variable genes (IGHV). Thus, they contrasted CK cases with 3 or 4 aberrations (low-CK and intermediate-CK, respectively) who followed aggressive disease courses only in the presence of TP53abs. At the other end of the spectrum, patients with CK and +12,+19 displayed an exceptionally indolent profile. Building upon CK, TP53abs and IGHV gene somatic hypermutation status, we propose a novel hierarchical model where patients with high-CK exhibit the worst prognosis, while M-CLL lacking CK or TP53abs as well as CK with +12,+19 show the longest overall survival. In conclusion, CK should not be axiomatically considered unfavorable in CLL, representing a heterogeneous group with variable clinical behavior. High-CK with =5 chromosomal aberrations emerges as prognostically adverse, independently of other biomarkers. Prospective clinical validation is warranted before finally incorporating high-CK in risk stratification of CLL.

Homeobox genes HOXA9 and MEIS1 are evolutionarily conserved transcription factors with essential roles in both hematopoiesis and leukemogenesis. They act as dominant cooperating oncoproteins that cause acute leukemias bearing MLL translocations and to a lesser extent T-cell acute lymphocytic leukemia (ALL) characterized by other gene fusions. Overexpression is associated with an adverse prognosis in adults. In childhood, the genes have only been investigated in leukemias bearing MLL translocations. The aim of this study was to determine whether overexpression extends to leukemic subtypes other than the MLL-positive subtype in childhood. We use quantitative real-time PCR methodology to investigate gene expression in 100 children with acute leukemias and compare them to those of healthy controls. We show that abnormally high HOXA9 and MEIS1 gene expression is associated with a variety of leukemic subtypes, including various maturation stages of B-cell ALL and cytogenetic types other than the MLL-positive population, thus suggesting that the genes are implicated in the development of a broad range of leukemic subtypes in childhood. In addition, we show that HOXA9 and MEIS1 overexpression are inversely correlated with relapse and overall survival, so the genes could become useful predictive markers of the clinical course of pediatric acute leukemias.

Newer cytogenetic scoring systems for myelodysplastic syndromes (MDSs), like cytogenetic stratification of the revised international prognostic scoring system (IPSS-R) or monosomal karyotype, may also improve outcome prediction after hematopoietic SCT (HCT). We compared the prognostic value of specific cytogenetic abnormalities, IPSS-R karyotype and monosomal karyotype for HCT outcome in 98 patients with MDS and AML post MDS. Higher-risk IPSS-R karyotype, 3q21q26 and transformation to AML before HCT were associated with increased cumulative incidence of relapse (CIR), whereas OS was adversely influenced by del 5q/-5, abnormalities of chromosomes 11 and 17 and cytogenetic IPSS-R very poor category. Karyotype with ⩽2 abnormalities and no abnormalities of chromosomes 3, 5, 7, 11 and 17 was an independent prognostic factor of lower CIR (hazard ratio (HR)=0.2, P=0.01) and longer OS (HR=0.5, P=0.03). In conclusion, some specific cytogenetic abnormalities and high cytogenetic complexity, as reflected by IPSS-R very poor karyotype, rather than monosomal karyotype, were associated with higher CIR and shorter OS after HCT. Conversely, results were encouraging in patients lacking those abnormalities, who may be very good candidates for HCT.

Chronic myeloid leukemia (CML) in childhood is a rare event, accounting for fewer than 5% of all childhood leukemias. The hallmark genetic abnormality of CML is the Philadelphia (Ph) chromosome, wh...

The NQO1 C(609)T germline polymorphism resulting in a lowering of enzyme activity may confer susceptibility to MDS. To assess this association, we performed a case-control study including 330 Greek patients with de novo MDS and 416 healthy donors, using a Real-Time PCR genotyping method. Focusing on cytogenetic aberrations most commonly found in MDS, we retrospectively genotyped 566 MDS/AML patients carrying -5/del(5q), -7/del(7q), +8, del(20q) and -Y. The case-control analysis revealed no differences in NQO1 genotype distribution. Interestingly, a 6-fold increased frequency of the homozygous variant genotype was observed among patients with isolated trisomy 8 (p

Monosomal karyotype (MK) has recently been reported to identify a distinct subset of acute myeloid leukemia (AML) with adverse prognosis. We retrospectively evaluated the frequency of MK in a large cohort of 549 unselected AML cases diagnosed in our department over a period of 13 years and explored potential associations with clinicobiological features and outcome. MK was found in 62 of 549 cases (11.3%), with all but one assigned to the unfavorable cytogenetic risk category; 57 of these 62 MK cases had a complex karyotype. Comparison with a subgroup of AML cases, who had unfavorable karyotypic profiles yet without MK (non-MK) and who were treated uniformly with similar, "3+7"-based regimens, revealed significant (P0.05) associations between MK and advanced age, low white blood cell count at diagnosis, and inferior overall survival (6.5 vs. 15 months for non-MK cases). In conclusion, MK defines a sizeable subset of patients with unfavorable cytogenetics who exhibit a distinct clinical profile, even in direct comparison with other unfavorable karyotypes.

Chronic lymphocytic leukemia (CLL) displays extreme clinical heterogeneity likely reflecting the underlying biological heterogeneity. For this reason, intense research efforts have addressed progno...

Recurrent cytogenetic abnormalities in chronic lym- phocytic leukemia (CLL), namely deletions of chromo- somes 11q, 13q, 17p and trisomy 12 (+12), define sub- groups of patients with different clinical behavior and response to treatment. 1 We and others previously report- ed a minor proportion of CLL cases with co-existing tri- somies of chromosomes 12 and 19 who share specific clinico-biological characteristics. 2-4 However, since the cohort was small, no definitive conclusions could be drawn. Here, we analyzed a large, multi-institutional series. We confirm and significantly extend previous observations through the identification of subgroups of +12 CLL cases harboring particular concurrent trisomies demonstrating distinctive clinico-biological profiles. We analyzed an unselected cohort of 4486 CLL patients with available classic cytogenetic (n=4285) or high-density 250K single nucleotide polymorphism (SNP)-array (n=201) data. We identified 712 cases (16% of the cohort) carrying +12. 5 Median time from diagnosis to cytogenet- ic/SNP analysis was 1.5 months (range 0-194); the major- ity of cases included in survival analysis were untreated prior to testing (94%). The study was approved by the local Ethics Review Committees. Details of the study cohort and the methodologies used are provided in the Online Supplementary Appendix.

The category of myelodysplastic syndromes/myeloproliferative diseases (MDS/MPD) is a relatively new group of malignant hematologic diseases developed by the World Health Organization. These hematologic disorders lack the BCR/ABL fusion gene, although they can be associated with chromosomal translocations that involve genes encoding other protein kinases. Imatinib mesylate was recognized as a potent inhibitor of some of those kinases. We present a patient with a previously treated acute myeloid leukemia, who, after a 9-year-long remission, developed an MDS/MPD with normal karyotype, which initially responded to imatinib mesylate. Translocation t(12;13)(p12;q14) was detected after loss of response to imatinib treatment. Translocation t(12;13) is rare. It has been described in several hematologic malignancies including chronic myelomonocytic leukemia but not in MDS/MPD, previously described as Philadelphia-negative chronic myelogenous leukemia. Moreover, the correlation of this molecular abnormality with loss of efficacy of imatinib is unique in the literature.

Transferrin receptor (TfR)-1 and 2 mRNA and CD71 (TfR1) expression was analyzed in 118 CLL patients. Ninety-five out of 109 analyzed cases expressed CD71, mostly at a high level; 60% of CD71 (+) cases were IGH-mutated. All samples were TfR1 mRNA (+); TfR2-alpha/beta mRNA was detected in, respectively, 52/102 and 100/109 cases. Competitive RT-PCR showed widely divergent levels of TfR1 mRNA in cases with high CD71 expression, alluding to postrtanscriptional control of TfR1 expression in CLL. The almost uniformly high CD71 expression in CLL is in keeping with the activated status of neoplastic cells, regardless of IGH mutational load.

One-hundred-and-thirty typical, unselected CLL cases were studied by conventional cytogenetic analysis. Seventy-three patients (56.2%) had normal karyotype ('normal sub-group'), while 57/130 patients (43.8%) had abnormal karyotype. Twenty-two of 57 patients (38.6%) carried more than one abnormality. Six novel chromosomal abnormalities were detected in five patients: (i) t(3;13)(q14;q34); (ii) t(Y;11)(q12;q23), del(13)(q12q14); (iii) dic(3;11)(p21;q23); (iv) t(3;5)(q29;q23); (v) t(3;22) (p21;q13); and (vi) t(1;13)(p12;q12). Three of five patients carrying novel translocations had progressive disease. The true biological and clinical significance of novel chromosomal abnormalities remains to be determined.

Herewith, we present a rare case of a 6-day-old male neonate, born at 40 weeks’ gestation, in whom the diagnosis of congenital acute lymphoblastic leukemia (cALL) was established, characterized by the immunophenotype of the most immature B-cell precursors (pro pro-B-ALL). The initial clinical/laboratory manifestations were leucocytosis, hepatosplenomegaly, anemia, thrombocytopenia, cutaneous lesions known as “leukemia cutis,” and CNS involvement. Cytogenetic testing revealed an extremely rare novel complex chromosomal translocation t(2:4:11) (p21:q21:q23) associated with the rearrangement of MLL gene. The child was treated with the chemotherapy protocol INTERFANT ‘99 but one month after birth developed multiple organ failure and died. The cutaneous lesions were located on the right cheek and left forearm and included nontender, magenta tan papules and nodules with sizes ranging from 3.5 to 1.7 cm (Figure 1). The liver was palpable 4 cm while the spleen 5 cm below the costal margins. The history of the child during the antenatal period was uneventful. The mother first trimester TORCH results were negative and there was no history of exposure to radiation or drugs during pregnancy. Laboratory investigations were: hb 13.5 g/dL, hct 40.2%, WBC 169.000/mm 3 (89% lymphoblasts, 5% neutrophils, 6% lymphocytes), and PLT 42.000/mm 3 . The reticulocyte count was 2.5%, and LDH was 2.265 U/L. Blood and urine culture were negative and serologic testing was not indicative of congenital infection with toxoplasma, rubella, CMV, HSV, syphilis, Epstein Barr, HIV, HAV, HBV, and HCV. Chest radiograph and cranial ultrasound were normal. Bone marrow aspiration revealed

Band q22 of chromosome 21 contains the RUNX1 gene (alias AML1 or CBF-alpha; CBFa), which is critical for hematopoiesis and undergoes fusion with a variety of genes in de novo and therapy-related ac...

Pediatric oncology patients are often iron overloaded, due to the multiple blood transfusions necessary during the course of chemotherapy. Our aim is to report the efficacy and safety of deferasirox, an oral iron chelator, in this patient group. Deferasirox was administered to 13 children with malignancies in remission and iron overload. Ferritin, blood urea nitrogen, creatinine, transaminases, and bilirubin were recorded at 4- to 8-week intervals, and hepatic and cardiac iron overload were assessed with magnetic resonance imaging before initiation of treatment. Deferasirox was administered for an average of 6 months (SD=4.5; range, 0.3 to 18.2). Two children presented with skin rash, 1 with gastrointestinal disturbances, and 1 with fully reversible acute renal failure. The mean monthly rate of change in ferritin levels was -10.8 μg/L before initiation of treatment (95% confidence interval [CI], -19.8 to -1.8; P=0.02) and -93.6 μg/L during deferasirox treatment (95% CI, -118.1 to -69.1; P0.001). The difference in the monthly rate of change in ferritin levels before and after treatment initiation was -82.8 μg/L (95% CI, -111.6 to -53.9; P0.001). Deferasirox was effective in reducing the iron burden. The adverse effects were easily monitored and managed. Further studies are warranted to investigate the effect of deferasirox on mortality and morbidity in this population.

Novel chromosomal aberrations in Philadelphia negative cells of chronic myelogenous leukemia patients on imatinib: report of three cases

Coexistence of trisomies of chromosomes 12 and 19 in chronic lymphocytic leukemia occurs exclusively in the rare IgG-positive variant

The chronic lymphocytic leukemia (CLL) immunoglobulin repertoire is uniquely characterized by the presence of stereotyped B-cell receptors (BCRs). A major BCR stereotype in CLL is shared by immunoglobulin G-switched cases utilizing the immunoglobulin heavy-chain variable 4-34 (IGHV4-34) gene. Increased titers of IGHV4-34 antibodies are detected in selective clinical conditions, including infection by B-cell lymphotropic viruses, particularly Epstein–Barr virus (EBV) and cytomegalovirus (CMV). In this context, we sought evidence for persistent activation by EBV and CMV in CLL cases expressing the IGHV4-34 gene. The study group included 93 CLL cases with an intentional bias for the IGHV4-34 gene. On the basis of real-time PCR results for CMV/EBV DNA, cases were assigned to three groups: (1) double-negative (59/93); (2) single-positive (CMV- or EBV-positive; 25/93); (3) double-positive (9/93). The double-negative group was characterized by heterogeneous IGHV gene repertoire. In contrast, a bias for the IGHV4-34 gene was observed in the single-positive group (9/25 cases; 36%). Remarkably, all nine double-positive cases utilized the IGHV4-34 gene; seven of nine cases expressed the major BCR stereotype as described above. In conclusion, our findings indicate that the interactions of CLL progenitor cells expressing distinctive IGHV4-34 BCRs with viral antigens/superantigens might facilitate clonal expansion and, eventually, leukemic transformation. The exact type, timing and location of these interactions remain to be determined.

Two novel chromosomal translocations were identified in 2 patients with chronic lymphocytic leukemia (CLL). Case 1: 60 year-old male, stage Rai 0/Binet A, with mutated immunoglobulin heavy (IgH) and lambda (Iglambda) light chain genes; karyotype: 46, XY, t(9;12)(q12;p11) [3]/ 46, XY [22]. Case 2: 56 year-old male, stage Rai 2/Binet B, with mutated IgH and unmutated Iglambda genes; karyotype: 46, XY, add(10)(q26), t(13;18)(q14;q21) [8]/ 46, XY [27]. Although both translocations are novel, the involved breakpoints (especially 13q14 and 18q21) have been reported to participate in various aberrations in CLL patients. Aberrations affecting bands 9q12 and 12p11, as in case 1, are generally rare.

We examined transferrin receptor (TfR) 1 and TfR2 mRNA expression in 50 acute myeloid leukemia (AML) patients by RT-PCR, with primers specific for exons 15-17 (TfR1), 3-5 (TfR2-alpha) and 4-5 (TfR2-beta) of the corresponding gene. There were 4/50 TfR1-negative (-), 3/50 TfR2-alpha mRNA (-) and 13/50 TfR2-beta mRNA (-) cases; only three cases were TfR1/2 mRNA (-). No significant correlations were identified between TfR2-beta mRNA negativity and specific FAB subtypes, karyotype or attainment of complete remission. These findings suggest that: (i) TfR2 expression is not restricted to erythroid cells, and (ii) iron import proteins might complement each other in AML cells.

Myelodysplastic syndrome (MDS) in patients treated for acute promyelocytic leukemia (APL) is a rare event. We describe a patient with APL who developed MDS 40 months after entering complete remission (CR). Karyotypic analysis revealed monosomy 5 and 7, which are cytogenetic changes usually occurring after the use of alkylating agents. The patient had received only anthracyclines as potential leukemogenic drugs. A review of the literature on t-AML/MDS occurring after successful therapy for APL showed three similar cases. These observations suggest that anthracyclines may cause t-AML/MDS similar to that induced by alkylating agents.

Clonal aberrations in Ph(−) metaphases have been reported rarely in patients with chronic myeloid leukemia (CML) after treatment with interferon-alpha (IFN-α) [1-3]. In contrast, the incidence of P...

Abstract 3915 Although chromosomal translocations (CTRAs) are detected relatively frequently, CLL is conspicuous for the paucity of recurrent CTRAs. The biological and clinical significance of CTRAs in CLL remains uncertain, likely reflecting the underlying genetic heterogeneity. Here we reappraise CTRAs in CLL in a cohort of 893 patients with reliable classic cytogenetic data, selected with an intentional bias towards cases carrying CTRAs. The study group included 568 males and 325 females with a median age of 65.4 years; information about Binet stages at diagnosis was available for 761 cases: A, 650/B, 76/C, 35; 419/646 (64.8%) cases with available data carried mutated IGHV genes (M-IGHV). The median time from diagnosis to classic cytogenetic analysis was 2.3 months; FISH data was available for 556/893 cases. Overall, 311 cases were found to carry ≥1 CTRAs; 193/311 (62%) cases carried balanced CTRAs whereas the remaining 118 cases (38%) carried ≥1 unbalanced CTRAs. The most frequent chromosome breakpoints were 13q (14% of all translocation partners, TPs), followed by 14q (6%), 18q (5%), 17q (3.5%) and 17p (3.5%); notably, CTRAs involving chromosome 13q showed a wide spectrum of TPs. When compared to CTRA- cases (n=582), CTRA+ cases exhibited a significantly higher prevalence of complex karyotype (three or more structural and/or numerical aberrations; 112/311 CTRA+ cases vs. 46/582 CTRA- cases, p Disclosures: No relevant conflicts of interest to declare.