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Hemoglobinopathies are among the most common hereditary diseases worldwide, with high prevalence in the Mediterranean basin, Africa, and Asia. Although they are rare in the indigenous central European population, they have become much more common in Germany recently through the immigration of millions of people from endemic regions.In a long-term study (1971-2007), 100,621 hemoglobin analyses were performed and retrospectively evaluated. Basic clinical and hematological information were provided by the participating physicians. The hemoglobin defects were characterized with hematological and biochemical methods, as well as by DNA analysis in selected cases (from the mid-1980's onward). 73% of the analyses were performed in patients with an immigration background, 27% in patients of German ethnic origin.34,228 persons, or 34% of those studied, were found to have a hemoglobinopathy. Most cases involved thalassemia syndromes (25,798 cases, 25.6%); the second most common type was a structural abnormality of hemoglobin (8,430 cases, 8.4%). This study provides the first broad overview of the occurrence, spectrum, and geographical distribution of hemoglobinopathies in Germany.These data show that hemoglobinopathies are a relevant health problem in the population of Germany today. This is not an epidemiological study, and thus it is unknown to what extent these data are representative. Because hemoglobin defects are of widely diverse genetic and clinical types, specialized laboratory analysis is needed to diagnose them correctly and provide a basis for proper therapeutic decisions.

The most common forms of hereditary persistence of fetal hemoglobin synthesis (HPFH) and delta beta zero-thalassemia result from simple deletions of the beta-globin gene cluster or from point mutations in the gamma-globin gene promoters. These naturally occurring mutants extend our understanding of globin gene regulation and hemoglobin switching. Furthermore, they provide the opportunity to test in vivo hypothetical switching models that are based on the experimental approach. We report here a family with delta beta zero-thalassemia from Turkey with a complex rearrangement of the beta-globin gene cluster that involves two deletions of 11.5 kb and 1.6 kb, and an inversion of 7.6 kb. The larger deletion removes both the delta-and the beta-globin genes with 3′ flanking sequences, whereas the smaller deletion affects DNA of unknown function. The inversion contains the entire L1 repeat 3′ of the beta-globin gene. There are structural motifs near the breakpoints (introduction of an “orphan” nucleotide, multiple direct and inverted repeats) suggesting a nonhomologous type of recombination event. The hematologic phenotype and the molecular structure of the rearranged beta-globin gene cluster are consistent with a competitive relationship between the fetal and the adult globin genes and/or with the translocation of enhancer sequences into the gamma-globin gene region.

T-cell receptor (TCR) delta gene rearrangements are observed in more than 80% of acute lymphoblastic leukemia (ALL) patients. Moreover, a preferential usage of specific genetic elements has been shown in different ALL subtypes: V delta 1 DJ delta 1 rearrangements predominate in T-ALL, while most B-precursor ALLs show a recombination of V delta 2 to D delta 3. Recently we have proposed a strategy for the detection of minimal residual disease (MRD) based on the isolation of clonospecific probes following the in vitro amplification of V delta 1 DJ delta 1 junctions by polymerase chain reaction (PCR) and now have adapted this method to the preparation of specific V delta 2 D delta 3 fragments. In the present study, clonospecific probes were generated from 11 T-ALL and 16 cALL patients (21 children, 6 adults). The sensitivity of these 27 probes in detecting residual leukemia cells varied between 10(-4) to 10(-6) as determined by semiquantitative evaluation of dilution experiments. PCR analysis of 55 bone marrow (BM) and peripheral blood (PB) samples obtained from the 27 patients during complete clinical remission showed the following results: (1) Evidence for MRD was obtained in the BM of all patients (eight of eight) investigated 2 to 6 months after remission induction and also in 6 of 11 cases on maintenance therapy 7 to 19 months after diagnosis. (2) In contrast, all patients but one (10 of 11) analyzed 6 to 41 months after the termination of treatment lacked apparent evidence for leukemia DNA; the exception was a girl exhibiting 10(-4) to 10(-5) residual cells in her PB 5.5 years after diagnosis. (3) Longitudinal analysis in nine patients disclosed marked individual differences in the intervals between achievement of clinical remission and complete eradication of the leukemia cell clone. (4) Differences in the duration of MRD were not associated with distinct clinical-hematologic features. (5) Detection of residual disease by PCR proceeded clinical relapse in two cases.

Human severe combined immunodeficiency (SCID) patients were analyzed by a polymerase chain reaction assay for their recombination capability at the DHQ52-JH region of the immunoglobulin heavy chain locus. Five patients with B cells (B+ SCID) exhibited a recombination pattern also observed in healthy persons. In contrast, six patients lacking B cells (B- SCID) showed a grossly altered rearrangement pattern characterized by the (partial) absence of regular DHQ52-JH recombinations and the presence of abnormal rearrangements. These events were caused by deletions surpassing the boundaries of immunoglobulin coding elements and thus resemble the pattern of deletional recombinations previously described in SCID mice.

The treatment of acute leukemias in child-hood has been very successful in the Federal Republic of Germany. Multicenter trials for both, acute lymphoblastic leukemia (ALL) and acute nonlymphoblastic leukemia (AML), have existed for more than 10 years now and since about 1980 almost 90% of children have been treated within the two BFM trials [1, 2] or the COALL trial [3]. Intensive induction therapy has led to results which belong to the best cure rates so far achieved in these childhood malignancies. An overall disease-free survival of 70% for ALL and at least 50% for AML has been documented. For ALL, conventional chemotherapy is able to cure even a distinct part of those children where late relapses occur (gt;1/2 year after the end of maintenance therapy). This is not true, however, for children suffering from ALL with early relapses and those with AML for whom the outcome of therapy following a relapse is very unfavorable.

In 21 newly diagnosed children with type 1 diabetes mellitus initial hemoglobin A1c-concentrations, mean insulin requirements during the first 10 days of treatment to recompensate carbohydrate metabolism, duration of glucosuria after diagnosis and duration of remission were determined. Initial hemoglobin A1c-concentration and both mean insulin requirement during the first 10 days of treatment and duration of initial glucosuria showed a highly significant positive correlation. A highly significant, negative correlation was found between the duration of remission and both the mean insulin requirement during the first 10 days of treatment and the duration of initial glucosuria. Thus the present results together with previous findings suggest that the severity of initial metabolic decompensation in diabetes mellitus type I seems to determine at least in part the duration of remission.

In 35 children with long-standing diabetes mellitus, a significant correlation was found between the hemoglobin A1c (HbA1c)—and the 24-hour urinary glucose excretion. By contrast, 11 newly diagnosed diabetic children had grossly elevated HbAlc-concentrations, but no correlations could be established between the levels of HbAlc and the duration of symptoms, blood glucose, glycosuria, ketonuria and the acid-base status. However, HbA1c and C-peptide were significantly correlated. The elevated HbA1c-concentrations decreased towards normal in all of these 11 children after 2–3 months following adequate therapy. The results suggest that the determination of HbA1c. may serve as a valuable metabolic control index in children with long-standing diabetes mellitus, but adds little information in newly diagnosed diabetic patients. For the individual diabetic child during the early treatment period, HbA1c may be the index of choice for adequacy of metabolic control.

Cytogenetic analysis of a patient with chronic myelocytic leukemia revealed a translocation (21; 22) (q 22; q 11) without a detectable involvement of chromosome 9. By in-situ hybridization studies, however, we demonstrate a reciprocal translocation of sequences from chromosome 9 (c-abl) to Ph1 and chromosome 22 (bcr) to 9, respectively. These observations suggest a consistent participation of chromosome 9 in the Ph1 translocation, regardless of the cytogenetic subtype.

In the first part we reviewed both the molecular basis of granulocyte function and the inborn defects. The present chapter summarizes our knowledge of the secondary defects of chemotaxis, opsonisation, phagocytosis and intracellular microbicidal activity.

From 1972-1983 53 patients underwent bone marrow transplantation. The median age was 18 years (3-41). 27 patients suffered from severe aplastic anaemia, 22 patients had acute leukaemia and 4 patients had chronic granulocytic leukaemia in chronic phase. Out of 22 patients with acute leukaemia, 2 had florid leukaemia, 2 had an early relapse and 18 patients were in first or second remission of their disease. 2/53 patients received a syngeneic transplant, 51/53 patients an allogeneic transplant. 47/51 patients had a HLA-A, B, C-identical, MLC-negative sibling donor, 1/51 had a HLA-A, B-C-identical, MLC-positive sibling donor, 2/51 a HLA-phaenotypical identical parental donor and 1/51 a HLA-identical, MLC-negative unrelated donor. The comparison of the results obtained in patients with severe aplastic anaemia transplanted from 1972-1979 with those transplanted from 1980-1983 shows that the bone marrow transplantation has to be performed in an early stage of the disease before the patients become multiple transfused, sensitized and severely infected and that the conditioning regimen for polytransfused patients has to be more intensive than in untransfused patients. From the patient group transplanted 1972-1979, only 1/14 patients is a long-term survivor in contrast to 8/13 patients transplanted from 1980-1983. 11/22 patients with acute leukaemia are alive between more than 5 years and 14 days after bone marrow transplantation. Only 1/4 patients, who were transplanted not in remission, is alive.(ABSTRACT TRUNCATED AT 250 WORDS)

The insight in the function and dysfunction of granulocytes lately arouses more and more interest. This report summarises our present knowledge. In the first of two chapters the authors review the molecular basis of granulocyte function and the inborn defects of chemotaxis, opsonisation, phagocytosis and intracellular killing of bacteria and fungi.

Restriction fragment length polymorphisms (RFLPs) of the X-chromosome genes hypoxanthine phosphoribosyl transferase (HPRT) and phosphoglycerate kinase (PGK) were studied in 34 female patients with primary myelodysplastic syndromes (MDS). Twelve patients (35%) were heterozygous at the HPRT or PGK loci for BamHI or BglI RFLPs, respectively. In eight patients showing PGK polymorphisms, clonality was determined by X-chromosome inactivation analysis. These included patients from different morphologic subtypes: four with refractory anemia (RA), two with RA and ring sideroblasts (RARS), one patient with RA with excess of blasts (RAEB), and one with chronic myelomonocytic leukemia (CMML). A monoclonal pattern of X-chromosome inactivation was observed in seven cases. In a further case characterized by bone marrow hypoplasia, peripheral blood (PB) leukocytes were polyclonal in origin. Following low-dose cytarabine therapy, reversion to polyclonal hematopoiesis was observed in a case of RAEB indicating the presence of residual normal hematopoietic stem cells with the capacity for marrow reconstitution. The clonal relation of lymphoid and granulocyte/monocyte lineages was studied directly in two cases of CMML exhibiting somatic mutations of N-ras or Ki-ras oncogenes. By selective oligonucleotide hybridization to ras gene sequences amplified in vitro by the polymerase chain reaction, a mutated ras allele was demonstrated in PB granulocytes, monocytes, and B and T lymphocytes of both patients. We conclude that MDS arise from a multipotent hematopoietic stem cell with the potential for myeloid and lymphoid differentiation.

Funktion und Eigenschaften des Hamoglobins stehen in enger Beziehung zur Architektur des Molekuls. Die Kenntnis der vollstandigen atomaren Struktur erlaubt es, die Mechanismen des Gastransportes und der Stabilitat des Hamproteins zu erklaren. Die Identifizierung von Strukturvarianten hat dazu wesentlich beigetragen. In gleicher Weise sind auch die klinischen Krankheitsbilder, die durch pathologische Effekte anomaler Hamoglobine verursacht werden, einer Erklarung zuganglich.

Granulocyte function of 10 diabetic children has been investigated. At the time of testing the diabetes was in poor control. Five children were retested one week later after adjustment of diet and insulin dose. In contrast to some reports we did not find a phagocytic defect in the ingestion of particles, but the capacity of intracellular killing of Staphylococcus aureus was impaired. Chemotaxis was also reduced whereas the NBT-index and intracellular killing of Candida albicans were normal. Better control of the diabetes led to an improvement of bactericidal killing capacity.

Restriction endonuclease mapping of chromosomal DNA has been used to determine whether the α-globin gene deletion or non-deletion form of α-thalassemia is the underlying molecular defect in individuals of two unrelated German families with α-thalassemia syndromes. The obtained DNA pattern in all cases indicated loss of α-globin genes resulting in-α/αα,--/αα, and--/-α genotypes in αthalassemia-2, α-thalassemia-1, and Hb H individuals respectively. The chromosomes showing loss of one α-globin gene in α-thalassemia-2 and Hb H disease were characterized by the so-called rightward deletion form exhibiting loss of a 3.7 kb DNA fragment in the α-gene cluster.

Bei 11 Neugeborenen mit G Trisomie (Down-Syndrom) wurden saulenchromatographisch Hamoglobinanalysen zur exakten quantitativen Bestimmung der Hamoglobine A1, A2 und F durchgefuhrt. Die Ergebnisse wurden zu den Hamatokritkonzentrationen in Bezichung gesetzt. Neben einer deutlichen Polyglobulie hatten alle Neugeborenen mit G Trisomie signifikant erhohte Mengen an HbA1 (35,5±6,6%) bzw. HbA2 (0,79±0,32%) im Vergleich zu gesunden Neugeborenen (HbA1=17,74±4,56%, HbA2=0,25±0,2%). Demnach wird der ontogenetische Wechsel in der Synthese von γ-Polypeptidketten zu β- und δ-Ketten beim Down-Syndrom zu einem fruheren Zeitpunkt eingeleitet als bei Normalen. Postnatal lauft diese Entwicklung mit entsprechendem Vorsprung weiter. Die starkere HbA-Synthese bei Kindern mit G Trisomie in der Perinatalperiode steht moglicherweise in direkter Beziehung zur gesteigerten Erythropoese. Demgegenuber scheint die Chromosomenaberration keinen spezifischen Einflus auf Einleitung und Ablauf der ontogenetischen Ablosung der Hamoglobine zu nehmen.

The Philadelphia (Ph1) chromosome, the cytogenetic hallmark of chronic myeloid leukemia (CML), has also been detected in a significant number of acute lymphoblastic leukemias (ALL). Using in situ hybridization, we demonstrate that in accordance with observations in CML the Ph1 chromosome in ALL patients is the result of a consistent translocation of the c-abl oncogene to the Ph1 chromosome. Southern blot analysis using bcr probes, however, suggests that Ph1-positive ALL includes heterogeneous leukemic subtypes: six ALL patients showed bcr rearrangements as observed in CML; in three other patients recombination involving 5′ bcr sequences could be demonstrated, but the corresponding translocated 3′ bcr sequences were not detectable. A third group of five patients did not show any bcr rearrangements at all. Northern blot analysis using RNA from three Ph1-positive ALL patients revealed that in the leukemic cells of two patients larger c- abl mRNA transcripts were present, as in CML. In the RNA of one patient without a detectable bcr rearrangement, only the normal c-abl mRNA transcripts are present. The observed heterogeneity in bcr rearrangements of this group of Ph1-positive ALL patients is in contrast with the consistent results obtained in more than 50 Ph1- positive CML patients investigated in chronic and acute states.

Population genetic studies in Saudi Arabia are performed for EsD, GPT, AcP, ADA, AK, 6-PGD, PGM, C3, Tf, Hp, Gc, Pi, Bf, Hb, ABO-blood groups and Rh-factor, level of the third component of complement and immunoglobulins. The data are compared with reported frequencies in European and African populations.

The second occurrence of Hb M Milwaukee is reported in two members of a German family who had cyanosis since early childhood. Contrary to earlier reports, Hb M Milwaukee exhibits a distinct heat instability. It is suggested, that in this family the variant resulted from a new mutation.

Bericht uber die Beobachtung einer neuen HbM-Variante bei einem 4jahrigen Jungen mit kongenitaler Cyanose. Die Strukturaufklarung ergab Identitat mit HbM Saskatoon = β63 His → Tyr. Bei keinem der untersuchten Familienangehorigen war eine Blutfarbstoffanomalie vorhanden, so das es sich um eine neue Mutation handelt. HbM Erlangen weist eine normale Sauerstofftransportfunktion auf. Es ist kombiniert mit einer kompensierten Hamolyse, die wahrscheinlich durch eine erhohte Instabilitat des abnorm strukturierten Hamoglobins verursacht wird. Gleichzeitig fand sich eine verminderte Aktivitat der NADH-Methamoglobinreduktase.

Durch Adsorption und Dialyse gereinigte und durch Seitzfiltration keimfrei gemachte Oxyhamoglobinlosungen von menschlichen Neugeborenen und Erwachsenen wurden vergleichend auf die Geschwindigkeit der Spontanoxydation bei 37° und pH 6,8 in Anwesenheit von Luft untersucht. Beide Hamoglobinarten oxydierten sich gleich schnell, was im Gegensatz zu der Tatsache steht, das Nabelschnurhamoglobin durch Oxydationsmittel etwa doppelt so schnell zu oxydieren ist.

Von Erythrozyten des Erwachsenen- und Nabelschnurblutes wurden nach Zentrifugation in einer schmalen hohen Saule die Zellen der oberen und unteren Schicht isoliert und in ihnen quantitative Daten ermittelt. Die Erythrozyten der unteren Schicht besitzen im Vergleich zu den Zellen der oberen Schicht einen signifikant hoheren mittleren Hamoglobingehalt, eine hohere mittlere Hamoglobinkonzentration und ein niedrigeres mittleres Zellvolumen. Die Umlagerung der Erythrozyten wahrend der Zentrifugation ist demnach im wesentlichen eine Funktion der groseren Dichte von Einzelzellen der Gesamtpopulation. Im Hinblick auf die Alterstrennung konnte an Hand der Zahl der Retikulozyten sowohl fur Erwachsenen- als auch fur Nabelschnurblut eine sichere Anreicherung von jungen Zellen in der oberen Schicht bestatigt werden. Ferner lies sich fur das Blut von jungen Sauglingen bzw. Neugeborenen durch quantitative Bestimmung der Erythrozyten mit adultem Hamoglobin eine Anhaufung von alten Erythrozyten in der untersten Zellschicht nachweisen.

An Erythrocyten von Neugeborenen und von gesunden und anamischen Sauglingen, Kindern und Erwachsenen wurde die Fahigkeit zur Reduktion von intracellular erzeugtem Methamoglobin gepruft. 1. In Bestatigung alterer Angaben fand sich bei Neugeborenen eine signifikant geringere Reduktionsfahigkeit als bei einem Kollektiv von Kindern und Erwachsenen. Diese Minderleistung war bei Glucose und bei Lactat als Substrat in gleicher Weise nachweisbar. Es handelte sich nur um eine quantitative Differenz, nicht etwa um eine qualitative Abweichung des zugrundeliegenden Fermentmechanismus. 2. Durch Untersuchung anamischer Sauglinge und Kleinkinder lies sich zeigen, das die Hb-Konzentration in der Zelle entscheidend fur die Ruckbildungsfahigkeit ist: mit fallender Hb-Konzentration steigt die Reduktionsgeschwindigkeit steil und annahernd linear an. Bei einer Hb-Konzentration von 24% lauft die Reduktion 6mal so rasch ab wie bei dem Normalwert von 34%. In die gefundene Gesetzmasigkeit ordnen sich die Werte der Erythrocyten von Erwachsenen, Kindern und Sauglingen glatt ein. Die oben erwahnte “Minderleistung” der Nabelschnur-erythrocyten ist nur eine Manifestation der hohen Hb-Konzentration in diesen Zellen. 3. Hypochrome Erythrocyten sind nicht einfach nur Zellen mit geringerem Hamoglobingehalt, sondern weisen eine echte Steigerung des Reduktionsmechanismus auf. 4. Erythrocyten junger Sauglinge konnen Galaktose besser utilisieren als Erythrocyten Erwachsener.

Es werden Methode, Bedingungen und Mechanismus der Differenzierung von Methamoglobin und Oxyhamoglobin in einzelnen Erythrocyten auf dem Objekttrager beschrieben.

Summary Heinz body formation by incubation of blood with acetylphenylhydrazine was more pronounced in erythrocytes of newborns than in erythrocytes of adults, the ratio being approximately 5:1. In haemolysates cord haemoglobin was denatured only slightly faster by acetylphenylhydrazine than was adult haemoglobin. By differentiating HbA-cells from HbF-cells in blood smears from newborns with the acid elution technic it could be shown that Heinz body formation proceeded nearly as fast in erythrocytes containing HbA as in erythrocytes containing HbF. HbF therefore does not play a significant role for the enhanced Heinz body formation in red cells of newborn infants. Since the amount of reduced glutathione has no decisive significance either, there must be some other characteristic property of the red cells of newborns making them labile in this respect.

In einer norddeutschen Familie, die cyanotische Individuen in 3 Generationen aufweist, wurde HbM als Ursache der Cyanose festgestellt. Ein Kind konnte von Geburt an beobachtet werden; es entwickelte erst im Ablauf einiger Wochen die charakteristische Cyanose. Daraus war abzuleiten, das die Anomalie in derβ-Kette des Hamoglobins liegen muste. Dies lies sich im Hybridisierungsexperiment mit Hundehamoglobin als zutreffend erweisen. Die Untersuchung der Peptide der durch Gegenstromverteilung aus Globin isoliertenβ-Kette mittels „fingerprint“ ergab ein anomales PeptidβT7. Die quantitative Aminosaureanalyse dieses Peptids zeigte, das darin Histidin fehlte, dagegen Tyrosin vorhanden war, woraus folgt, das in Position 63 derβ-Kette ein Histidin-Tyrosin-Austausch vorliegt. Das entspricht den Verhaltnissen in HbM Saskatoon.

Es wird uber die erste deutsche Familie mit α-Thalassamie berichtet, wobei ein fast 8jahriges Madel in der 3. Generation an einer HbH-Krankheit mit Persistenz von Hb Bart's erkrankt ist. In Ubereinstimmung mit anderen Untersuchungen last sich aus der Familienkonstellation albeiten, das die HbH-Krankheit durch Kombination von einem „aktiven“ mit einem zweiten, aber „stummen“ α-Thalassamie-Gen entsteht. Aus den quantitativen Verhaltnissen der Polypeptidketten zueinander wird die Moglichkeit diskutiert, ob nicht die α-Thalassamie mit Persistenz von Hb Bart's eine Sonderform der HbH-Krankheit darstellt, bei der gleichzeitig auch die Synthese derβ-Ketten gehemmt ist.

Vetter, U., Heinze, E., Beischer, W., Kohne, E., Kleihauer, E. and Teller, W. M. (Centers of Paediatrics and Internal Medicine, University of Ulm, FRG). Haemoglobin A1c: a predictor for the duration of the remission phase in juvenile insulin dependent diabetic patients. Acta Paediatr Scand, 69:481, 1980.—Increased HbA1cconcentrations in diabetic patients indicate retrospectively a poor metabolic control during the preceding 2–3 months. In the present study attempts have been made to use the HbA1c concentration at the time of diagnosis as an indicator of the duration of the remission phase in 23 juvenile diabetic children. The regression analysis revealed a significant negative correlation between the initial HbA1c concentrations and the duration of the remission phase defined as no glucose excretion, an insulin requirement of less than 0.5 U/kg/day and detectable serum C-peptide concentration (r= -0.84, p < 0.001). The results suggest that the initial HbA1c concentration may serve as a useful indicator to predict the duration of the remission phase in juvenile-onset diabetic patients

Es wird uber eine einfache und recht empfindliche elektrophoretische Methode zum Nachweis von Katalase berichtet.

Die vonMatthies an Kaninchenerythrocyten entdeckte Ausnutzung von Formaldehyd zur fermentativen Reduktion von Methamoglobin (HbIII) in roten Zellen wird an Erythrocyten menschlicher Neugeborener und Erwachsener bestatigt. Bei einer Formaldehydkonzentration von 5·10−3 mol geht die HbIII-Reduktion rascher vor sich als mit Glucose. Neugeborenen-Erythrocyten verhalten sich qualitativ wie die Erythrocyten von Erwachsenen. Quantitativ besteht eine Minderleistung, wie schon aus Untersuchungen mit Glucose und Lactat gelaufig ist. In hypochromen Erythrocyten ist die HbIII-Ruckbildung durch Formaldehyd wie die durch Glucose oder Lactat stark gesteigert. Die Steigerung geht weit uber das hinaus, was aus der verringerten Hb-Beladung der Zellen erwartet werden konnte. Es wird auf die merkwurdige Tatsache aufmerksam gemacht, das die uberschiesende Fermentaktivitat in hypochromen Erythrocyten nur bei Prozessen gefunden wird, die mit einer Wasserstoffubertragung unter Vermittlung von Codehydrogenase I (DPN) verknupft sind. Uber Codehydrogenase II (TPN) ablaufende Prozesse zeigen diese Steigerung nicht.

Hb Wien besitzt als elektrophoretisch schnell wanderndes instabiles Hamoglobin im Vergleich zu manchen anderen instabilen Varianten einige abweichende Eigenschaften. Diese bestehen in kaum erhohter Spontanoxydation und einem praktisch normalen Methamoglobinspektrum. Die in der Cyanmethamoglobinform nicht vom HbA1 abweichende Hitzeempfindlichkeit ist wahrscheinlich auf den stabilisierenden Effekt der Ligandenbildung mit Cyanid zuruckzufuhren. Das fetale Hamoglobin entspricht quantitativ und in der intracellularen Verteilung anderen bei instabilen Varianten mitgeteilten Befunden. Das HbA2 ist normal.

A patient is presented who manifested the typical clinical and pathological features of congenital immunodeficiency and agranulocytosis (reticular dysgenesia). Treatment under gnotobiotic conditions enabled the measurement of immunogical parameters up to the 17th week of life with the following results: negative skin test, low response to phytohaemagglutinin, weak response in the mixed leukocyte culture and very few E rosettes. Peripheral lymphocytes and lymphocytes in the lymphatic tissues were markedly decreased. Humoral immunoglobulins and plasma cells in the organs were decreased. The in vitro culture of hemopoietic cells showed a diminished content of myelopoietic progenitor cells ("committed stem cells"). It is concluded that the disease may be primarily a defect of stem cells with regard to differentiation in myelopoiesis or lymphopoiesis.

Selective depletion of T cells from marrow grafts is an attractive approach to reduce the incidence and severity of GvHD. Recent studies in man clearly indicate that this approach is valid, opening the way to perform BMT across HLA barriers (1,2,3). However, this initial experience also reveals an increased risk of graft failures after transplantation of T cell depleted marrow, in particular when HLA nonidentical donors are used (4). We report similar experience obtained in 24 patients transplanted with in vitro processed marrow from HLA matched and mismatched donors, using lectin agglutination and/or rosetting by sheep red cells for T cell depletion.