Martínez Ja

Absence of platelet response after eradication of Helicobacter pylori infection in patients with chronic idiopathic thrombocytopenic purpura

Eradication of Helicobacter pylori infection has been associated with the correction of thrombocytopenia in patients with idiopathic thrombocytopenic purpura (ITP). We have analysed the response to eradication of H. pylori in a series of 56 adult patients with chronic ITP. Forty patients had H. pylori infection (71%) that was eradicated in 23 of 32 evaluable patients (72%). Platelet counts did not significantly vary according to H. pylori treatment outcome. Three of 56 patients (5%) achieved a partial response attributable to H. pylori eradication. Therefore, detection of H. pylori infection should not be routinely included in the initial work‐up of ITP.

Early infections in adult patients undergoing unrelated donor cord blood transplantation

Early transplant-related mortality after cord blood transplantation from unrelated donors (UD-CBT) is close to 50%, mainly due to infectious complications. We have studied the incidence and characteristics of early infections (before day 100) in a series of 27 adult patients (median age 30 years, range 16–46) undergoing UD-CBT at a single institution. All 27 patients experienced at least one infectious episode and 18 (66%) suffered a severe infection. Bacteremia occurred in 55% of patients (13 with Gram-positive and 11 with Gram-negative microorganisms). Eleven of 19 CMV-seropositive patients (58%) developed CMV antigenemia and one patient had CMV disease. Fungal infections were documented in three patients (11%), comprising invasive fungal infections in two cases and a localized esophagitis in one. Ten patients (37%) died before day 100 after transplantation. Infection was considered the primary cause of death in four patients (sepsis by Acinetobacter spp. bacteremia in three cases) and contributed to death in another four. The most striking findings in this series were the high incidence of, and mortality due to multiresistant Acinetobacter spp. and the low incidence of and lack of mortality due to CMV disease. This report confirms that infection is a major complication in adults undergoing UD-CBT.

Critical evaluation of ASO RQ-PCR for minimal residual disease evaluation in multiple myeloma. A comparative analysis with flow cytometry

We have analyzed the applicability, sensitivity and prognostic value of allele-specific oligonucleotide real-time quantitative PCR (ASO RQ-PCR) as a method for minimal residual disease (MRD) assessment in patients with multiple myeloma (MM), comparing the results with those of multiparameter flow cytometry (MFC). A total of 170 patients enrolled in three consecutive Spanish trials achieving at least partial response after treatment were included. Lack of clonality detection (n=31), unsuccessful sequencing (n=17) and suboptimal ASO performance (n=51) limited the applicability of PCR to 42% of cases. MRD was finally investigated in 103 patients (including 32 previously studied) with persistent disease identified by PCR and MFC in 54% and 46% of cases, respectively. A significant correlation in MRD quantitation by both the techniques was noted (r=0.881, P<0.001), being reflective of treatment intensity. Patients with <10−4 residual tumor cells showed longer progression-free survival (PFS) compared with the rest (not reached (NR) vs 31 months, P=0.002), with similar results observed with MFC. Among complete responders (n=62), PCR discriminated two risk groups with different PFS (49 vs 26 months, P=0.001) and overall survival (NR vs 60 months, P=0.008). Thus, although less applicable than MFC, ASO RQ-PCR is a powerful technique to assess treatment efficacy and risk stratification in MM.

Busulfan plus cyclophosphamide followed by autologous blood stem-cell transplantation for patients with acute myeloblastic leukemia in first complete remission : a report from a single institution

PURPOSE To determine if peripheral-blood stem cells (PBSC) collected during the recovery of standard induction and consolidation chemotherapy in acute myeloblastic leukemia (AML) can be used as a safe tool for autologous transplantation, and to study aspects of the autologous blood stem-cell transplantation (ABSCT) procedure and their results in AML patients in first remission. PATIENTS AND METHODS Twenty-four AML patients in first remission received busulfan (BU; 16 mg/kg) and cyclophosphamide (CY; 200 mg/kg) followed by ABSCT. PBSC were collected by continuous-flow leukaphereses after induction and consolidation courses. RESULTS The median numbers of mononuclear cells (MNCs) and colony-forming unit granulocyte-macrophage (CFU-GM) administered were 6 x 10(8)/kg and 11 x 10(4)/kg, respectively. ABSCT induced engraftment in 22 patients and there were two graft failures. The median times to reach a polymorphonuclear (PMN) leukocyte count of 0.5 x 10(9)/L and a platelet count of 50 x 10(9)/L were 13 and 19 days, respectively. Fatal hepatic veno-occlusive disease (VOD) was observed in two cases. Other toxicities were mild and uncommon. Twelve patients relapsed between 1 and 9 months posttreatment. Actuarial disease-free survival (DFS) and actuarial risk of relapse at 30 months were 35% (95% confidence interval [CI], 25% to 45%) and 60% (95% CI, 50% to 72%), respectively. CONCLUSION These preliminary results show the fast hematopoietic recovery and the low infectious and hemorrhagic morbidity associated with the procedure and strongly suggest that ABSCT may be as effective as autologous bone marrow transplantation (ABMT) in AML. However, further strategies for reducing leukemic relapse must still be investigated.

Morbidity and transplant-related mortality of CBV and BEAM preparative regimens for patients with lymphoid malignancies undergoing autologous stem-cell transplantation

CBV and BEAM are the two most frequently used regimens for patients with lymphoma undergoing autologous hematopoietic stem-cell transplantation (ASCT). This study compared their morbidity and transplant-related mortality (TRM) in 113 patients with non-Hodgkins lymphoma (69) and Hodgkins disease (44) undergoing ASCT between 1990 – 2004. CBV (cyclophosphamide, 6000 mg m−2; VP-16, 750 mg m−2; and high-dose BCNU, 800 mg m−2) was administered to 75 patients and 38 received BEAM (BCNU, 300 mg m−2; VP-16, 800 mg m−2; cytarabine, 800 mg m−2; melphalan, 140 mg m−2). Patients in the BEAM group had a significantly higher median age (p = 0.002) and were more heavily treated before ASCT (p = 0.003). More patients showed active disease at transplant in the BEAM group (p = 0.04). Sinusoidal obstruction syndrome (SOS) was more frequent in the CBV group (11% vs 0%, p = 0.048). There were 20 (18%) transplant-related deaths, 18 in the CBV and two in the BEAM group. Infectious complications (12 patients, seven with pneumonia) and SOS (four) were the most frequent causes of death. The cumulative incidences of TRM were 25% in the CBV and 7% in the BEAM group (p = 0.02). CBV thus produced a higher incidence of SOS and TRM than BEAM in this series.

A phase II clinical trial of carboplatin infusion in high-risk acute nonlymphoblastic leukemia.

Carboplatin (CBDCA) is a second-generation platinum drug that has been shown to be useful when used as a continuous infusion in treatment of refractory adult leukemia. We report on the effectiveness of continuous infusion CBDCA, 300 mg/m2/d x 5 days, as evaluated in nine patients with secondary acute nonlymphocytic leukemia (ANLL) (seven previous myelodysplastic syndrome and two treatment-associated ANLL), three ANLL patients in first relapse, six refractory ANLL, and nine patients with blastic phase of chronic myelogenous leukemia (BP-CML). All patients were considered assessable. The response rate was 44% (eight complete remissions [CRs], four partial remissions [PRs]). Median duration of postchemotherapy neutropenia was 36 days (range, 18 to 45). Therapy was well tolerated, and toxicity was mainly hematologic and nondose-limiting. Despite prolonged neutropenia, severe infections were rarely seen, and most patients were managed as outpatients. Twelve patients had nausea and vomiting, two had symptomatic hypomagnesemia, and one patient showed reversible ototoxicity. Because of substantial antileukemic activity and unusual extrahematologic toxicity, CBDCA appears to be an effective second-line agent in the treatment of ANLL and should be considered for upgrading to first-line treatment regimens.

Unrelated donor cord blood transplantation in adults with chronic myelogenous leukemia: results in nine patients from a single institution

The potential role of unrelated donor cord blood transplantation (UD-CBT) in adults is not well established. We report the results of UD-CBT in nine adult patients with chronic myeloid leukemia (CML). The median age was 27 years (range, 19–41 years), and the median weight was 62 kg (range, 45–78 kg). At transplant, six patients were in chronic phase (five in first, and one in second), two in blast crisis, and one in accelerated phase. Eight had received intensive chemotherapy, and three had undergone autologous peripheral blood hematopoietic stem cell transplantation. Four had received interferon with no cytogenetic response, and only three underwent UD-CBT within 1 year of diagnosis. After serological typing for class I antigens, and high-resolution DNA typing for DRB1, the degree of HLA match between patients and cord blood (CB) units was 4/6 in six cases and 5/6 in three cases. The median number of nucleated cells infused was 1.7 × 107/kg (range, 1.2 to 4.9 × 107/kg), and was above 2 × 107/kg in only two cases. All patients received thiotepa, busulfan, cyclophosphamide and anti-thymocyte globulin as conditioning; cyclosporine and prednisone for graft-versus-host disease (GVHD) prophylaxis; and G-CSF from day +7 until engraftment. All seven evaluable cases engrafted. The median time to reach an absolute neutrophil count ⩾0.5 × 109/l and ⩾1 × 109/l was 22 days (range, 19–52 days) and 28 days (range, 23–64 days), respectively. In the four patients evaluable for platelet recovery time to levels of ⩾20 × 109 platelets/l, ⩾50 × 109 platelets/l, and ⩾100 × 109 platelets/l, these ranged from 50 to 128 days, 60 to 139 days, and 105 to 167 days, respectively. Three patients developed acute GVHD above grade II, and three of the five patients at risk developed extensive chronic GVHD. Four patients, all transplanted in chronic phase, remain alive in molecular remission more than 18, 19, 24 and 42 months after transplantation. These preliminary results suggest that UD-CBT may be considered a reasonable alternative in adults with CML who lack an appropriate bone marrow donor. Bone Marrow Transplantation (2001) 27, 693–701.

Marked reduction in the incidence of hepatic veno-occlusive disease after allogeneic hematopoietic stem cell transplantation with CD34(+) positive selection.

Veno-occlusive disease of the liver (VOD) is a common and severe complication of allogeneic hematopoietic stem cell transplantation (HSCT). To determine the incidence of, and the risk factors for the development of VOD, we performed a retrospective analysis of a series of 178 patients, who underwent allogeneic HSCT at our institution between 1990 and 1999. Busulfan and cyclophosphamide constituted the conditioning regimen most frequently administered. Bone marrow was the source of stem cells in 129 patients (73%), and peripheral blood (PBSC) in 49 patients (27%). Thirty-one patients of the PBSC group received CD34+ positively selected grafts. Most patients were given cyclosporin A and methotrexate (MTX) as graft-versus-host disease (GVHD) prophylaxis. Overall, 30 patients (17%) developed VOD. In univariate analyses, the incidence of VOD was significantly higher in recipients of unmanipulated grafts (20% vs 0%; P = 0.01), in patients with active malignant disease at transplantation (24% vs 9%; P = 0.03), in recipients of marrow from unrelated donors (33% vs 15%; P = 0.03), in patients grafted with bone marrow (21% vs 6%; P = 0.03), and in those receiving MTX as GVHD prophylaxis (21% vs 6%; P = 0.05). Under multivariate analysis, only CD34+ positive selection (P = 0.0004) and the status of the disease at transplant (P = 0.03) were statistically significant variables for the development of VOD. We conclude that CD34+ positively selected PBSC transplantation could result in a marked reduction in the incidence of VOD after allogeneic HSCT. Bone Marrow Transplantation (2001) 27, 983–988.

FLAG-IDA regimen (fludarabine, cytarabine, idarubicin and G-CSF) in the treatment of patients with high-risk myeloid malignancies

Forty-five patients with high-risk myeloid malignancies (32 acute myeloid leukemia and 13 high-risk myelodysplastic syndromes) were treated with fludarabine, cytarabine, idarubicin, and G-CSF (FLAG-IDA). Twenty-four (53%) patients achieved complete remission (CR), and five (11%) partial remission. Infection predominantly with pulmonary involvement was the most common regimen-related toxicity. Mucositis (15 patients) and pulmonary toxicity (19 patients) were the most frequently observed non-hematologic side effects. There were four early deaths and 12 patients presented with resistant disease. Overall survival (OS) at 12 months was 40%. The FLAG-IDA regimen shows evident antileukemic activity in patients with high-risk myeloid malignancies with acceptable toxicity.

Prolonged molecular remission after PML/RARα-positive autologous peripheral blood stem cell transplantation in acute promyelocytic leukemia: is relevant pretransplant minimal residual disease in the graft?

The contribution of residual malignant cells contaminating the autologous graft with the occurrence of post-transplant relapse in acute myeloid leukemia (AML) is still unclear. The presence of a specific molecular marker (the PML/RARα rearrangement) in acute promyelocytic leukemia (APL) offers the opportunity to investigate better the pathogenesis of disease recurrence after transplant. We report an APL patient who received high-dose chemotherapy and peripheral blood stem cell (PBSC) autograft in second hematologic remission. Two leukaphereses that tested PML/RARα positive by RT-PCR were obtained during the post-reinduction hematopoietic recovery, while the patient also tested PCR positive in the BM, and was reinfused after myeloablative chemotherapy (BUCY4), when the patient had spontaneously converted to PCR negative in the marrow. At present, he remains in continuous molecular and hematologic remission 22 months after PBSC transplantation. This is the second report of an APL patient who was transplanted in molecular remission with a PML/RARα-positive PBSC autograft. As in the previous report, the prolonged clinical and molecular remission experienced post-transplant suggests that autologous PBSC infusion is still worthy of consideration for patients with APL in spite of the detection of PML/RARα-positive cells in the PBSC collections. Possible underlying mechanisms and the potential role of molecular monitoring of the graft, as well as the host, before and after transplant, in patients with APL undergoing autologous HSCT are also discussed.