We analyzed data of 76 consecutive patients with myelodysplastic syndrome (MDS) and isolated del(5q) (n ¼ 66) or del(5q) plus one additional chromosomal abnormality (n ¼ 10) included in our MDS database over the last 26 years. The median age of our patient population was 66.8 years. The male to female ratio was 1:1.7. In all, 14 patients (18%) had advanced MDS with an increased medullary blast count. A total of 17 patients (22%) had significant dysplasia in the nonmegakaryocytic cell lines. Nearly half of the study population showed erythroid hypoplasia in the bone marrow. The projected median survival of patients with isolated del(5q) is 146 months for a median followup of 67 months. Patients with an increased medullary blast count and those with an additional chromosomal abnormality have a significantly shorter overall survival (24 and 45 months, respectively) than patients with isolated del(5q). We did not find survival differences for different cytogenetic breakpoints, nor did the amount of dysplasia have an impact on survival in our population. In total, 29 patients have died. Deaths occurred primarily due to transformation into acute leukemia, infection, or cardiac failure. Our data support the current definition of a separate entity of MDS with del(5q) that has been suggested by the World Health Organization.

Objectives: C-X-C motif chemokine receptor 4 (CXCR4)-targeted radioligand therapy (RLT) has already been applied to advanced blood cancers, such as multiple myeloma or diffuse large B-cell lymphoma. We herein present a series of patients with advanced Tcell lymphoma (TCL), who were scheduled for CXCR4-directed therapy as conditioning regimen, followed by hematopoietic stem cell transplantation (HSCT). Methods: Four patients with advanced, heavily pretreated and relapsed TCL (2 males, 2 females; median age, 50 years) without suitable alternative therapeutic options underwent CXCR4-directed PET and pretherapeutic dosimetry. We then conducted CXCR4-targeted RLT in combination with allogeneic (3/4, 75%) or autologous (1/4, 25%) HSCT. One patient also underwent radioimmunotherapy targeting CD66 to enhance therapeutic efficacy. We investigated safety, best response, progression-free (PFS) and overall survival. Results: Pretherapeutic dosimetry indicated lymphoma absorbed doses of up to 33.2 Gy from CXCR4-targeted RLT. Except for one patient developing tumor lysis syndrome along with transient grade 3 kidney failure, no acute toxicity, allergic reactions or other adverse events were recorded during therapy. One patient developed septicemia and subsequently died 16 days after RLT, while engraftment was achieved in the remaining 3 subjects (75%). During follow-up, partial response was recorded in 1 patient (33.3%) and complete metabolic response in 2/3 (66.7%, with one patient also receiving additional radioimmunotherapy). Median PFS was 7 months (range, 4 -25 m). After a median followup of 54 m (range, 4 -56 m), three patients were still alive at date of censoring.Conclusions: For advanced, heavily pretreated TCL, CXCR4-directed RLT may serve as an effective conditioning therapy prior to HSCT and can cause substantial anti-lymphoma activity, leading to remarkable response in selected cases.

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The survival of patients with myelodysplastic syndromes is strongly affected by chromosomal abnormalities. Patients with an isolated del(5q31) have a favourable prognosis that worsens with the addition of another chromosomal abnormality. It has been reported that both patients with isolated del(5q31) and those with one single additional chromosomal abnormality achieve hematological and cytogenetic remissions with lenalidomide therapy. Whether this translates into improved overall survival of the patient population is unclear. We analysed data of 25 patients with myelodysplastic syndrome and complex chromosomal abnormalities including del(5q31) and show that their median survival is between 7 and 8 months, irrespective of the medullary blast count. Furthermore, we present data of a patient with complex karyotypic anomalies inclusive of del(5q31) treated with lenalidomide who achieved complete cytogenetic remission. This cytogenetic remission was diagnosed after 6 months, and the hematological response is ongoing at 9 months of therapy at a dose of 5 mg p.o. daily. We conclude that lenalidomide has the potential to induce sustained hematological and cytogenetic remissions in the poor prognosis MDS subgroup of del(5q31) patients with complex chromosomal anomalies and that this is likely to improve overall survival.

Lenalidomide has particular activity in patients with transfusion-dependent del(5q) myelodysplastic syndromes (MDS), but mechanistic information is limited regarding the relationship between erythroid and cytogenetic responses. We reviewed medical records from three distinct subgroups of del(5q) MDS patients who had unexpected effects with lenalidomide treatment: 1. two patients with complex karyotypes who achieved both cytogenetic remissions and transfusion independence; 2. two patients with 5q-syndrome who took lenalidomide for less than 12 weeks but remained transfusion independent for 15+ months still displaying del(5q) metaphases after 6 and 12 months; and 3. one patient who was a nonresponder on lenalidomide during treatment but became transfusion independent for 13+ months after discontinuation. All but the latter patient in this series had reduction of affected metaphases, suggesting that erythroid responses might be mediated by result from partial or complete suppression of the malignant clone, either directly or indirectly through modulation of the bone marrow microenvironment. These clinical observations illustrate the heterogeneity of del(5q)MDS pathogenesis and the diversity of lenalidomide responses within this patient subset.