Solomon S. Adler

Coexistence of leukemic reticuloendotheliosis and histiocytic lymphoma: a case report.

A 65‐year‐old woman had pancytopenia, splenomegaly, and an inaspirable bone marrow. Diagnostic evaluation demonstrated that she had both leukemic reticuloendotheliosis (LRE), or hairy cell leukemia, and an additional lympho‐reticular neoplasm, most likely a “histiocytic” lymphoma. The diagnosis of LRE was based on the histopathology of spleen tissue and of a bone marrow biopsy specimen. The diagnosis of diffuse “histiocytic” lymphoma was based on the histopathology of a splenic hilar and a mesenteric lymph node, tumor nodules in the kidney and spleen, and tissue from a mass obstructing a ureter. This is the first well‐documented association of a second lympho‐reticular neoplasm with LRE. Even relatively gentle treatment of the “histiocytic” lymphoma resulted in fatal pancytopenia, illustrating the restrictions on therapy imposed by the marrow impairment due to the LRE.

Anti-CFU-s Activity of Rabbit Anti-mouse Brain Serum: Mechanism of Action

In 1972, Golub (14) reported and others have subsequently confirmed (12,20,22,24) that antiserum raised against mouse brain tissue when incubated with mouse marrow cells prevents the pluripotent stem cells (CFU-s) from forming surface spleen nodules in lethally irradiated mice. The anti-CFU-s activity is not complement dependent (12,20,28). Van den Engh and Golub (28) have shown that anti-mouse brain serum does not interfere with the formation of granuloid/macrophage colony-forming units (CFU-c) in vitro. We have confirmed this and also found that rabbit anti-mouse brain serum (RAMBS) impairs the colony-forming capacity of spleen cells to the same extent as that of marrow cells (unpublished) and cannot inhibit the growth of erythroid colony-forming unit (CFU-e) cells in vitro (1).

High Remission Rate in Acute Myeloblastic Leukemia with Only Two Days of Chemotherapy

Twenty five patients with AML who had neither a history of toxic exposure or myelodysplasia were treated with a remission induction regimen consisting of two pulses of chemotherapy separated by 96 hrs. Each pulse consisted of cytarabine 2gm/m2 (at t=0 and t=12 hrs) with mitoxantrone [30mg/m2] administered immediately after the second cytarabine administration. Amifostine was administered three times a week [on Monday, Wednesday, and Friday] until the outcome of therapy was known. This regimen induced complete remissions in 15 of 17 patients less than 70 years of age and in 5 of 8 patients older than 70 years.

In vitro interactions between thymocytes and hemopoietic precursor cells

ZusammenfassungDie Wirkung von Thymozyten auf die Hämopoese wurde in Co-Kulturen aus Knochenmarkstammzellen von Mäusen und syngenen Thymuszellen für Vorläuferzellen der Granulozyten-Makrophagenreihe (CFU-GM) sowie für frühe (BFU-E) und späte (CFU-E) erythrozytäre Vorläuferzellen untersucht. Dazu wurden Co-Kulturen mit einer konstanten Zahl von Knochenmark-zellen bei zunehmender Thymozytenzahl angelegt. Zusätzlich wurde die Wirkung von Thymuszellen auf Kulturen mit optimalen oder suboptimalem Zusatz von humoralen Stimulationsfaktoren, der Einfluß einer Flüssigkeitskultur der Knochenmarkzellen mit Thymozyten vor Kultur im semisoliden Medium und der Effekt von radioaktiv bestrahlten und homogenisierten Thymuszellen untersucht.Das Wachstum der CFU-GM wurde im Vergleich zu anderen Vorläuferzellen durch Thymozyten weniger beeinflußt; bei bestimmten Mischungsverhältnissen von Knochenmarkszellen zu Thymuszellen konnte eine Hemmung nicht ausgeschlossen werden. Die stimulierende Wirkung auf BFU-E war deutlicher ausgeprägt als auf CFU-E; abgetötete Thymuszellen förderten das Wachstum der Vorläuferzellen nicht.Diese Ergebnisse weisen auf eine unterschiedliche Empfänglichkeit der verschiedenen hämopoetischen Vorläuferzellen im unfraktionierten Knochenmark für die in vitro-Stimulierung durch Thymuszellen hin. Außerdem scheinen nur lebensfähige Thymozyten das Wachstum der Vorläuferzellen in den untersuchten Kulturansätzen zu fördern.SummaryThe effects of thymocytes on in vitro hemopoiesis were evaluated by co-culturing mixtures of mouse marrow cells and syngeneic thymocytes for granulocyte/macrophage precursors (CFU-GM), and for early (BFU-E) and late (CFU-E) erythroid precursors. Co-cultures were studied which contained fixed numbers of marrow cells with increasing numbers of thymocytes as well as co-cultures in which the total number of cells was kept constant. In addition, the effects of thymocytes on cultures stimulated by optimal or suboptimal amounts of humoral factors, the effects of a liquid phase incubation of the marrow cells with thymocytes prior to semi-solid culture, and the effects of irradiated and disrupted thymocytes were studied.The growth of CFU-GM was stimulated by thymocytes less than the growth of the other progenitor cells studied; at most, minimal stimulation by thymocytes was detected and at some marrow cell: thymocyte (M:T) ratios inhibition was even suggested. The growth of BFU-E was more strongly and more consistently stimulated than that of CFU-E. Killed thymocytes did not effect stimulation of CFU-E or BFU-E.These studies suggest that, in unfractionated marrow cells, the various hemopoietic precursor cells differ in their sensitivities to in vitro stimulation by thymocytes. In addition, it appears that only viable thymocytes can effect stimulation of the hemopoietic precursors in the vitro culture systems used.

Hemopoiesis in Diffusion Chambers in Strontium-89 Marrow-Ablated Mice

Summary The numbers of pluripotent stem cells (CFU-S) and of the more differentiated granulocyte/macrophage elements in diffusion chambers (DCs) implanted into the peritoneal cavities of radio-89Sr-marrow-ablated mice are increased as compared to those in DCs implanted into cold-88 Sr-mar-row-ablated mice. These findings suggest that there is a systemic humoral response capable of stimulating hemopoiesis even in mice with aplastic marrows and whose hemopoiesis is localized to their spleens. The magnitude of this response and the promptness with which the response is manifest in DC growth suggests that marrow aplasia induced by 89Sr provides a stronger stimulus for proliferation of cells in DCs than does either cyclophosphamide or lethal external whole-body irradiation.

Rabbit anti-mouse brain serum (RAMBS): Lack of specific inhibition of late committed erythroid stem cells in culture (CFU-E)

ZusammenfassungHeterologe Antiseren gegen Hirngewebe der Maus hemmen die koloniebildenden pluripotenten hämopoetischen Stammzellen (CFU-S), jedoch nicht die Koloniebildung granulopoetischer dominierter Stammzellen in der Zellkultur (CFU-C). In der vorliegenden Arbeit wird gezeigt, daß heterologes Antimäusehirnserum vom Kaninchen keine spezifische Aktivität gegenüber determinierten erythropoetischen Stammzellen (CFU-E) der Maus aufweist.SummaryHeterologous antisera to mouse brain tissue have activity against mouse pluripotent hemopoietic stem cells (CFU-S), but not against granuloid/ macrophage committed precursor cells (CFU-C). In these studies we show that anti-mouse brain serum raised in a rabbit does not possess specific activity in vitro against late committed erythroid stem cells (CFU-E).

Antiserum to mouse pluripotent hemopoietic stem cells (CFU-S): Evidence for a role of complement in the inactivation of CFU-S in diffusion chambers

ZusammenfassungAntimäusehirnserum vom Kaninchen (RAMBS) zeigt Aktivität gegen pluripotente hämopoetische Stammzellen der Maus (CFU-S). Zur Abklärung des Mechanismus der Inaktivierung der CFU-S durch RAMBS wurden Knochenmarkzellen der Maus 1) mit RAMBS + Komplement (C), 2) mit RAMBS allein inkubiert. Die Beeinflussung des Wachstums der CFU-S wurde in Diffusionskammern 4 Tage nach Implantation in Mäuse untersucht. Durch Vorinkubation mit RAMBS + C wurden die CFU-S auf 20 %, durch Vorinkubation und mit RAMBS allein auf etwa 70% gegenüber unbehandelten Kontrollkammern gesenkt. Die Unterschiede im Zellwachstum deuten daraufhin, daß die Zugabe von Komplement den Hemmeffekt des Antiserums auf das CFU-S-Wachstums in Diffusionskammern verstärkt. Allerdings läßt sich dieser Hemmeffekt nicht nachweisen, wenn das CFU-S-Wachstum sofort nach der Inkubation mit RAMBS alleine oder mit RAMBS + C anhand der Milz-Koloniebildung letal bestrahlter Mäuse getestet wird. Es wird diskutiert, daß der C-bedingte Hemmeffekt durch Granulozyten und/oder Makrophagen bewirkt wird, die in den Diffusionskammern die mit IgG und C3 opsonisierten CFU-S vermehrten phagozytieren vermögen. Diese Befunde könnten für andere Systeme Bedeutung erlangen, zum Beispiel für Langzeit-in-vitro-Kulturen.SummaryAnti-mouse brain serum raised in rabbits (RAMBS) is known to contain activity against mouse pluripotent hemopoietic stem cells (CFU-S). To further elucidate the nature of the inactivation of CFU-S by RAMBS we treated mouse bone marrow cells with RAMBS alone, or with RAMBS plus complement (C), and observed the effects on the growth of CFU-S in diffusion chambers four days after implantation into the peritoneal cavities of mice. The chambers seeded with marrow cells that were treated with RAMBS + C contained less than 20 % of the number of CFU-S contained in their control chambers; but the chambers seeded with marrow cells that were treated with RAMBS alone contained about 70% as many CFU-S as did their control chambers. This difference in cell growth strongly suggests that the addition of C to RAMBS potentiates the antiserums suppressive effect on CFU-S growth in diffusion chambers, even though cells incubated with RAMBS alone demonstrate the same amount of CFU-S inactivation as that demonstrated by cells incubated with RAMBS + C when assayed immediately after incubation by the capacity to form surface spleen nodules in lethally irradiated mice. It is postulated that the C-mediated effect may be effected by granulocytes and/or macrophages in the diffusion chambers which are capable of phagocytosing IgG and C3-opsonized CFU-S. These findings might be extended to other systems, such as the long-term in vitro culture.

Bone marrow transplantation in leukemia: No longer a last resort

The search for cures for the various forms of cancer has long occupied the forefront of medical research. In leukemia, bone marrow transplantation is effecting cure in more and more types of leukemia and in different stages of the disease. This comprehensive review provides the reader with the background and rationale for transplantation, a description of the procedure itself and the potential complications, and a look at the state of the art.

Splenectomy and immunoprotective treatment in RFM mouse myelogenous leukemia

Abstract We studied the effect of splenectomy, a simple regimen of immunoprotection and a combination of the two on the survival of mice transplanted with RFM myelogenous leukemia. The following experimental procedures were performed on the test mice one month prior to the i.v. transplantation of 1 × 106 myelogenous leukemia cells: (1) splenectomies or sham splenectomies; (2) splenectomies with subsequent i.p. replacement of autologous spleens; (3) s.c. implantation of heat inactivated (65°C × 30 min) normal or leukemic syngeneic spleen tissue; or (4) the combination of splenectomy and s.c. implantation of spleen tissue. We found the following; (1) splenectomized mice had a median survival which was 2.2 times longer than that of their intact counterparts and 30% of the splenectomized mice were spared from developing the leukemia; (2) all splenectomized mice which had i.p. spleen implants developed leukemia, but their median survival was slightly longer than that of intact mice; and (3) the immunoprotective regimen used did not prolong the survival of any mice. We conclude that the spleen is an important organ in fostering the growth of RFM myelogenous leukemia cells and that the simple immunoprotective regimen studied was ineffective in altering the course of the disease.