Julia Lutz-Presno

Outcome of adults with acute lymphoblastic leukemia treated with a pediatric-inspired therapy: a single institution experience

Today, long-term survival is achieved in more than 80% of children aged 1–10 years with acute lymphoblastic leukemia (ALL). However, cure rates for adults, adolescents, and young adults remain relatively low, at only 40–50%. Adult regimens are typically less intense than their pediatric counterparts, because it is thought that adults do not tolerate drugs utilized in ALL treatment as well as children do. Adolescents with ALL have a better outcome when treated with pediatric protocols compared to adult protocols [1–3], and there are also suggestions of improved outcomes of adult patients with ALL treated with pediatric-inspired chemotherapy schedules [4]. Whether these improved outcomes are a result of higher doses of non-myelosuppressive drugs or whether they relate to other factors such as the experience of physicians or stricter adherence to scheduled treatments is unclear. We have tested the usefulness of an asparaginase-containing, pediatric chemotherapy-inspired protocol to treat adults with ALL, and report herein our results in a group of 80 patients studied and treated in a single institution during a 16-year period. All consecutive adult (18 years or older) patients with ALL studied and treated after March 1994 were prospectively included in the study. Patients were treated with a modification of the St. Jude Total XI combined chemotherapy program [5,6]; this schedule has an acceptable toxicity, employs affordable drugs, and can be delivered as an outpatient regimen, thus resulting in diminished costs. Induction was done with oral prednisone (40 mg/m/day6 28 days), intravenous (IV) vincristine (1.4 mg/m, capped to 2 mg, days 1, 8, 15, and 22), IV daunomycin (25 mg/m days 1, 8, and 15), intramuscular (IM) L-asparaginase (10 000 U/m days 4, 10, 15, and 19), IV etoposide (200 mg/ m days 22 and 29), and IV cytarabine (300 mg/m days 22, and 29). As consolidation therapy, IV methotrexate (MTX, 2.0 g/m, 2 h infusion, days 44 and 51) with oral folinic acid rescue (10 mg/m every 4 h, 612) was employed. Patients who did not attain complete remission (CR) after induction/consolidation were taken out of the study. The regimen of the early treatment is shown in Table I. As continuation therapy, oral 6-mercaptopurine (50 mg/ m/day) and oral MTX (20 mg/m/week) were employed, in addition to monthly pulses of rotating combinations of the drugs employed during induction (vincristineþdaunomycinþ asparaginase63 weekly doses; etoposideþ cytarabine62 weekly doses; methotrexateþ folinic acid61). Triple intrathecal therapy (MTX, dexamethasone, and cytarabine) was delivered on days 22 and 43 during induction and every 8 weeks along maintenance therapy, which was extended for 24 months. After June 2001 (when tyrosine kinase inhibitors [TKIs] became available in Mexico), Philadelphia chromosome-bearing (Ph1þ) patients were given imatinib (400 mg/day) or dasatinib (100 mg/day) 7 days after starting chemotherapy, and were assessed for stem cell transplant (SCT) once they achieved a

CD20 expression in B-cell precursor acute lymphoblastic leukemia is common in Mexican patients and lacks a prognostic value

Abstract Classification of acute lymphoblastic leukemia (ALL) by flow cytometric immunophenotyping characterizes the disease and delineates potential therapeutic intervention. We retrospectively analyzed CD20 expression in 143 patients with newly diagnosed precursor B-cell ALL. CD20 was observed in 61% of patients at diagnosis. There was no correlation between CD20 expression and age, white blood cell count, or cytogenetic abnormalities. Despite the fact that CD20-positive ALL patients had a tendency toward a worse outcome, there was no significant difference between patients with and without CD20 expression in 3-year overall survival 65 vs. 82% (P = 0.14), and cumulative incidence of relapse 36 vs. 18% (P = 0.3) in pediatric patients and 51 vs. 53% (P = 0.31) and 35 vs. 38% (P = 0.6) in adults, respectively. In conclusion, CD20 expression appears to be more common in Mexican patients with newly diagnosed precursor B-cell ALL higher than in Caucasian populations and lacks prognostic value.

Romiplostin may revert the thrombocytopenia in graft‐versus‐host disease

Abstract The thrombocytopenia ensuing during acute graft‐versus‐host disease (GVHD) is multifactorial and may significantly compromise the prognosis of the patient; non‐immune persistent thrombocytopenia has been considered as an adverse prognostic factor in GVHD. We describe here the case of a 10‐year‐old girl who developed steroid‐refractory thrombocytopenia and who responded promptly to the subcutaneous delivery of romiplostin. To the best of our knowledge, this is the first description of the usefulness of the peptibody in the setting of GVHD.

Moderate hyperprolactinemia is associated with survival in patients with acute graft-versus-host disease after allogeneic stem cell transplantation

Abstract Fasting serum prolactin (PRL) levels in response to metoclopramide (MCP) and lymphocyte cytokine profiles was studied in patients given allografts and their donors. Thirty normoprolactinemic volunteers (12–59 years) were studied: group 1, 10 healthy men; group 2, 8 males and 2 females with various hematologic diseases; and group 3, 3 males and 7 females HLA-identical sibling donors: PRL and cytokines were measured. Four surviving recipients developed acute graft-versus-host disease (GVHD) (+), and six did not. Before transplant Fasting PRL concentrations were higher in ‘future’ GVHD(+) recipients than in their donors (P < 0.001). The opposite was seen in response to MCP (P = 0.01). Donors had a predominant T-helper type 1 (Th1) cytokine profile compared with recipients (P ≤ 0.02), and GVHD(+) recipients had a greater tumor necrosis factor (TNF) value than GVHD(−) (P = 0.05). After transplant On days +30 and +100, a mild sustained rise in fasting PRL levels occurred only in GVHD(+) recipients (P ≤ 0.05) simultaneously with a transient rise in Th1 cytokines. GVHD(−) recipients had no changes. Donors with a Th1 cytokine profile might be more prone to induce GVHD in their recipients, and a mild sustained rise in PRL concentrations after transplantation in recipients GVHD(+) might participate in the amelioration of the severity of GVHD.

Reduced-Intensity Allografting in Childhood Acute Lymphoblastic Leukemia

We read with interest the article by Verneris et al. [1], concerning reduced-intensity conditioning (RIC) for allografting children with acute lymphoblastic leukemia (ALL). In their article, they gather data of 38 such patients. Despite the fact that they refer to some of our experience [2], they fail to include other articles from our group that include children with ALL allografted with a RIC regimen [3-6]. Since 1998, in 2 institutions within M exico (Centro de Hematologia y Medicina Interna de Puebla and Hospital Universitario de Nuevo Le on), we have allografted 44 children with ALL, using our RIC regimen that employs fludarabine, cyclophosphamide, and busulfan [2-5]. The median age is 6 years (range: 1-16), 13 females. In this group, we have allografted 14 patients in first complete remission (CR) and 30 in second or beyond CR. The median overall-survival (OS) of these 44 patients was 10 months, whereas the 85-month OS survival was 18%. Results for patients in first CR were substantially better than those obtained in relapsed individuals (45%versus 5%OSat 85months) (see Figure 1).These data are not different from those informed by Verneris et al. [1], and suggest that the malignant cells of some