Changing trends in allogeneic bone marrow transplantation for leukemia in the 1980s.

OBJECTIVE--To identify changes in practice and outcome of bone marrow transplants for leukemia in the 1980s. DESIGN--Comparison of key explanatory and outcome variables in five 2-year cohorts, from 1980 through 1981 to 1988 through 1989, using a large database of detailed clinical information. PATIENTS--Recipients (7788) of bone marrow transplants for acute lymphoblastic, acute myelogenous, or chronic myelogenous leukemia reported to the International Bone Marrow Transplant Registry, Milwaukee, Wis, by 185 transplant teams worldwide. RESULTS--Linear increases occurred during the periods 1980 through 1981 to 1988 through 1989 as follows with 95% confidence intervals: (1) transplants for chronic myelogenous leukemia from 14% +/- 2% to 35% +/- 2%; (2) transplants from unrelated donors from 1% +/- 1% to 7% +/- 1%; (3) preparative regimens without radiation from 3% +/- 1% to 30% +/- 2%; and (4) use of methotrexate plus cyclosporine to prevent graft-vs-host disease from 2% +/- 1% to 55% +/- 2%. Among recipients of human lymphocyte antigen-identical sibling bone marrow, the 2-year probability of treatment-related mortality decreased by 6% to 22%. The probability of relapse decreased from 46% +/- 6% to 38% +/- 6% in intermediate leukemia but did not change appreciably in early or advanced leukemia. Probabilities of leukemia-free survival improved from 51% +/- 4% to 57% +/- 3% in early leukemia, from 28% +/- 4% to 36% +/- 5% in intermediate leukemia, and from 12% +/- 4% to 18% +/- 5% in advanced leukemia. A separate analysis of a homogenous population of patients indicated that improvements in outcome in the 1980s were due to improvements in transplant practice rather than improved patient selection. CONCLUSIONS--Modest increases in leukemia-free survival rates occurred after human lymphocyte antigen-identical sibling bone marrow transplants in the 1980s. Improvements were due primarily to reductions in treatment-related mortality with little or no change in relapse risk. More effective antileukemia strategies and continued reductions in treatment-related toxic effects are needed.     

Sensory processing of backward-masking signals in children with language-learning impairment as assessed with the auditory brainstem response.

The purpose of this study was to examine the possible contribution of sensory mechanisms to an auditory processing deficit shown by some children with language-learning impairment (LLI). Auditory brainstem responses (ABRs) were measured from 2 groups of school-aged (8-10 years) children. One group consisted of 10 children with LLI, and the other group (control) consisted of 10 children with normally developing language. The ABR was elicited with a brief tone burst presented either alone (no-masking condition) or immediately followed by a longer duration noise burst (backward-masking condition). The primary dependent variable was the latency of wave V of the ABR. The mean latencies were not significantly different for the 2 groups in the no-masking condition. However, in the backward-masking condition, the mean latency for the LLI group was significantly increased relative to the mean latency for the control group. Thus, the presence of successive sounds delay the neural response in children with LLI. The explanation for this delay at the level of the brainstem is not known, but it may be due to disruption of synchrony, activation of alternate (less direct) pathways, increased inhibition, or some combination of these (or other) factors.     

High-dose caspofungin combination antifungal therapy in patients with hematologic malignancies and hematopoietic stem cell transplantation

Pneumocandins have concentration-dependent antifungal activity and higher dose of caspofungin (HD-CAP) in combination with other licensed antifungal therapy (OLAT) may improve response. Thirty-four patients who received HD-CAP were compared with 63 patients who received standard dose (SD)-CAP. There were no differences between the groups in either patient or disease characteristics. Significantly more patients in the HD-CAP arm had extrapulmonary infections (29 vs 8% in SD group; P=0.0053), and non-Aspergillus species infection (21 vs 6%; P=0.05) and had received prior antifungal therapy (71 vs 33%; P=0.0004). No serious adverse reactions were noted in patients receiving HD- or SD-CAP therapy. Twelve weeks after treatment commenced 44% had a complete or partial response compared with 29% in SD-CAP group (P=0.1). Logistic regression analysis showed a significant probability of a favorable outcome at 12 weeks in patients who received HD-CAP (OR 3.066, 95% CI, 1.092-8.61; P=0.033). This may in part reflect higher number of patients in HD group had received granulocyte-macrophage colony-stimulating factor (41 vs 14% in SD group; P=0.04) and/or interferon gamma (26 vs 5% in SD group; P=0.003) immune enhancement. Further studies are needed to evaluate efficacy of HD-CAP in severely immunosuppressed cancer patients with invasive fungal infections.     

Efficacy of prophylactic transfusions using single donor apheresis platelets versus pooled platelet concentrates in AML/MDS patients receiving allogeneic hematopoietic stem cell transplantation

Superiority of single-donor apheresis platelets (SDAP) over pooled platelet concentrates (PPC) transfusions is largely assumed, but unproven. We hypothesized that prophylactic SDAP and PPC transfusions are clinically equivalent after allogeneic hematopoietic stem cell transplants (HSCT). We studied all transfusions administered to 33 patients with AML/MDS during the first 100 days after busulfan-based, myeloablative HSCT. All donor-recipient pairs were ABO identical. Transfusion threshold was a platelet count < or =15 x 10(9)/l. The corrected increment (CCI) was used for all comparisons. Median time to platelet engraftment was 13 days (n=30). PPC transfusions (n=105) were ABO compatible, while 10% of 41 SDAP were not (P=0.006). Median post-transfusion platelet count was 51K/microl (5-118K) after SDAP and 36K/microl (3-115K) after PPC (P=0.0004). Median CCI was 14.178 (SDAP) versus 7.793 (PPC) (P=0.0001). Median time to another transfusion was 3 days (SDAP) and 2 days (PPC; P=0.3). In the week following any given transfusion, the median number of new transfusions was similar (n=2), as well as the need of further transfusion (16 versus 24%, P=0.2). A total of 17% of SDAP and 30% of PPC transfusions were labeled 'ineffective' (P=0.1). There were two non-lethal hemorrhage episodes (6%). SDAP transfusions produced better platelet counts, but SDAP and PPC were equally effective in preventing hemorrhage.