As part of a year-long celebration in honor of Blood's 70th anniversary, we are publishing a series of editorials written by past Editors-in-Chief of the journal. The authors reflect on their experience at Blood in light of the journal's publication history. Each of these special pieces will highlight and discuss the impact of one or more original research articles that had a significant influence on the field or that mark a pioneering scientific development in hematology that appeared in the journal during the author's term as Editor-in-Chief.

Several months ago, when I was asked to reflect on my tenure as Editor-in-Chief of Blood, the focus was to be on the science at that time and the subsequent impact it might have had. But reading through past issues of the journal, I could appreciate the dramatic advances and the rapidity with which new knowledge is brought to direct patient care. Today, more than 30 years later, it is an entirely different world. Consequently, some of my comments represent a very personal reflection on the times. And, because it has been more than 3 decades since my colleagues and I accepted the challenge, some recollections may be less accurate than I might wish.

The Editors

When the offices of Blood moved from New York to the University of Washington in Seattle, I’m sure many thought that the journal had fallen off the edge of the earth. I asked David Dale, Art Nienhuis, Hymie Nossel, and Bruce Chabner to join the effort as Associate Editors, and I asked Wendell Rosse to continue as Associate Editor to provide continuity and guidance. He graciously accepted and was invaluable. Unfortunately, very early into the first year, Hymie died unexpectedly, leaving a large hole that was eventually and ably filled by Harold Roberts. During the course of the 5 years, Wendell stepped down, and Sam Broder of the National Cancer Institute was added.

My personal philosophy was somewhat akin to that of the New York Times: we should print “all the [hematology] news that’s fit to print.” In other words, Blood should remain the most impactful hematology journal in the world and, in support of that, we should not make our acceptance rates so low as to drive sound research to competing journals in the field.

The Publisher

At that time, the journal was owned by the publisher Grune and Stratton. Each year, we would have to negotiate with the publisher for the numbers of “free” pages that the journal would be allowed. The cost of anything above the allotted number of pages would have to be borne by the American Society of Hematology, and so there was always some tension between the editors and the executive committee about the growth of the journal.

The journal appeared monthly in hard copy only. There was nothing like electronic submissions or e-pub in advance of hard copy. Each day, a mountain of mail would appear and had to be dealt with.

It quickly became clear that the journal needed to grow. In order to generate resources to increase journal space, we instituted what were then unpopular changes, including increases in page charges for those papers accepted, as well as (submission) charges for having papers reviewed, whether the paper was accepted or not. Whether these charges had an impact on the number of papers submitted, I don’t know. What is clear is that the numbers of submissions to the journal continued to rise each year, and by the end of our tenure, Associate Editors were handling at least 3 times the number of papers they had handled at the beginning. The next Editor-in-Chief, Art Nienhuis, wisely increased the number of Associate Editors!

There were other differences between the editors and the publisher. During the course of our tenure, we repeatedly rejected suggestions to enhance advertising revenue by allowing ads to be placed in between journal articles. Because of the claims of some of the advertising, which we believed were misleading, we adopted a policy of screening all ads before they were accepted for placement in the journal. This is probably less of an issue now, because the control of claims, particularly involving therapeutics, has to conform to Food and Drug Administration requirements.

The science

It is particularly difficult to pick from more than 2500 articles those that were the most impactful. Every editor will bring his or her bias (and different levels of knowledge of any given field) to the process. With that demurrer, I offer several examples of studies that led to advances in patient care. Some were clinical and some were basic. And, tragically, the journal also chronicled the march of HIV through the hemophilia community.

Hemostasis and thrombosis

I was surprised to see how much basic work in hemostasis and thrombosis there was. In this area, several articles stood out for their eventual clinical impact. Early work from Barry Coller’s laboratory1,2  led to the therapeutic agent abciximab. The authors concluded that “it is possible to profoundly inhibit platelet function by in vivo infusion of F(ab′)2 fragments of a monoclonal antiplatelet antibody without producing spontaneous hemorrhage or significant thrombocytopenia.”1p1456 The drug was very successful, but the outcome was a bit different in patients because thrombocytopenia was observed in some of them.

Other studies that continue to have an impact today include those from the Blood Research Institute of the BloodCenter of Wisconsin. Investigators there reported early cases of acquired von Willebrand disease3  and the effect of blood group on von Willebrand factor in normal people.4 

Similarly, the journal published some very practical suggestions such as the use of the dilute Russell viper venom time for the diagnosis of lupus anticoagulants.5 

Hemophilia

One report that struck me was the report on the effectiveness of factor VIII inhibitor bypassing activity.6  It wasn’t the fact that it worked (it did), but the fact that it was labeled a “familiarization study” designed for American physicians to become comfortable with the product. This, despite the fact that our European colleagues had been using factor VIII inhibitor bypassing activity for nearly 10 years at that point! This is a recurrent theme in hematology, it would seem.

Only by going back over the publications from those years did I appreciate the pattern that emerged of the spread of HIV infection in patients with hemophilia. This turned out to be devastating to that community and its effects are still being felt. We reported on the march of infection through this patient population.7-13  One takeaway was the relative “safety” of fresh frozen plasma and cryoprecipitate compared with factor concentrates, and those blood centers preferring fresh frozen plasma and cryoprecipitate usage had lower rates of HIV conversion in their patients.

And there were other surprises in retrospect. Investigators from South Africa demonstrated that using different isotopes to label platelets in patients with immune thrombocytopenic purpura gave different results.14  They concluded that platelet turnover is not always normal or increased in immune thrombocytopenic purpura but that it is low in severe disease. This observation, and simultaneous studies at the University of Washington by Ballem and Slichter,15  provided the insight that thrombopoietic stimulating agents might be effective in patients with refractory immune thrombocytopenia. And they were right.

Red cells and iron

Compared with today’s explosion of iron-related studies, it was a relatively quiet time. But studies that advanced the field included the effect of transfusion therapy on the recurrence of stroke in patients with sickle cell disease,16  which showed that persistent transfusion therapy dramatically reduced recurrent strokes and led to improved cerebral vascular architecture in children who had already had a neurologic event. These results pointed out the important contribution that red cell transfusions can make in the course of sickle cell disease; that is, a more predictable outcome than other currently available therapies, in my experience. Iron overload, and its management, is the necessary consequence. And a related study of the effect of hydroxyurea (HU) in patients with sickle cell disease was prescient in suggesting that “long-term HU therapy should be considered for severely affected adults with sickle cell anemia.”17p109 This was the forerunner to the large randomized, controlled study that was published in the New England Journal of Medicine in 1995.18 

Hematopoiesis

The 1980s were among the most interesting years for experimental hematology (as it was known then). The centers of excellence at that time were Melbourne, Toronto, and Vancouver. Colony-forming assays were in vogue, and the various colony-stimulating factors were being purified and, eventually, their genes cloned. The assay techniques were applied first to mice and then to humans. Long-term cultures were established in an attempt to understand how pluripotent stem cells were maintained. The same techniques were applied to leukemic cells in an attempt to understand the differences and similarities between the growth and differentiation properties of progenitor cells. A particularly good review came from 2 Editors-in-Chief to be.19 

Bone marrow transplantation

During 1983-1987, there were a number of reports on the results of bone marrow transplantation. Patients with acute leukemia in second remission were being salvaged with good survival rates.20-23  In one study, there was an ∼40% long-term disease-free survival rate in 57 patients who otherwise were not likely to do well with chemotherapy alone.

Cyclosporine was introduced to prevent graft-versus-host disease,24  and the same group reported on predictive factors in graft-versus-host disease.25  Researchers at the Fred Hutchinson Cancer Research Center in Seattle reported on the long-term consequences of bone marrow transplantation, showing that there were multiple endocrine and other abnormalities that affected growth and development after stem cell transplantation for leukemia.26  And, lastly, investigators from the University of Minnesota reported on stem cell transplantation in severe aplastic anemia and noted that there was less graft-versus-host disease in younger patients than in adults.27 

Hematologic malignancies

This is the area that probably has undergone the greatest advances over the past 30 years. There were important studies of cytogenetic changes in hematologic malignancies,28  including the report of an international workshop.29 

A surprising number of studies, perhaps more than 20, aimed to classify leukemias and lymphomas on the basis of recognition by antisera to cell surface antigens. These attempts were helpful in some areas, but not all. Horning et al stated the issue clearly for one example: “with our current immunologic methods, retrospective cell phenotyping analysis has not provided independent prognostic significance in diffuse large cell lymphoma. A prospective evaluation of similarly treated patients is needed to characterize the influence of phenotype fully and to determine its potential usefulness for therapy.”30p1209 This is but one example during that era of emerging technology that tried to identify patients for prognostication and, it was hoped, selection of treatment to optimize outcomes.31 

Molecular studies began to appear during our tenure. We published early molecular studies of the expression of specific oncogenes in leukemia as they became recognized.32,33  We also published seminal early work on the analysis of T-cell receptor gene rearrangement in T-cell chronic lymphoproliferative disorders and associated cytopenias.34,35 

Lastly, larger clinical trials in hematologic malignancies also appeared but were relatively infrequent.34  The study of Gottlieb et al clearly established the “increased effectiveness of vincristine, prednisone, l-asparaginase, and daunorubicin, as compared to this combination without daunorubicin, in the induction of complete response in adults with ALL.”36p267 Progress!

Epilogue

Looking back over the years, having the opportunity to edit the Society’s journal was one of the most rewarding experiences I’ve had in academic hematology. Our team of editors could see ahead, and we envisioned the journal to have more rapid publication, greater volume and diversity of topics, and an even greater clinical impact, without reducing the amount and quality of the basic science. It has all come true.

References

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