Registry of the German CLL Study Group
Registry of the German CLL Study Group
Long term follow-up of patients with chronic lymphocytic leukemia (CLL), B-prolymphocytic
 leukemia (B-PLL), T-cell prolymphocytic leukemia (T-PLL), Small lymphocytic lymphoma (SLL),
 T/Natural Killer large granular lymphocyte leukemia (T or NK-LGL), Hairy cell leukemia (HCL)
 and Richter's transformation
The most frequent primary endpoint in phase III trials of CLL is progression-free survival
 (PFS). However, the most important endpoint is overall survival (OS) which is usually a
 secondary endpoint in such trials. The outcome after progression is critical and responses to
 second and subsequent therapies may differ between the trial arms. Therefore it is essential
 to assess OS in addition to PFS. In addition, late toxicities, such as myelodysplastic
 syndrome (MDS) or acute myeloid leukemia (AML), Epstein-Barr virus (EBV)-associated
 lymphoproliferative disease or Hodgkin's disease, late opportunistic infections and second
 malignancies, are increasingly seen and are likely to differ depending on the intensity of
 therapy. Moreover, meta-analysis of several phase III trials with long follow-periods are
 desirable. Similarly, valid analyses of biological disease characteristics in relation to
 outcome are depending on large collections of clinical data with mature follow-up.

 The findings of the CLL8 study provide evidence that the addition of rituximab to
 chemotherapy with Fludarabine and Cyclophosphamide (FC) may prolong survival of patients with
 CLL. However, it also opens the question about whether applying such therapy might cause
 certain late toxicities and whether it improves longterm survival for patients with CLL.
 Moreover the outcome of subsequent therapies after various first line treatments with
 Fludarabine (F), FC, Bendamustine and Rituximab (BR) or Fludarabine, Cyclophosphamide and
 Rituximab (FCR) amongst others outside of clinical trials needs to be investigated further.

 Recently published phase III trials in CLL showed median observation times ranging from 22 to
 41 months, but most of the trials report observation times around 2 years only. For most of
 the phase III trials of the German CLL Study Group (GCLLSG) great efforts were made to
 implement an extended follow up in these trials, but due to administrative reasons the follow
 up is limited to at most 8 years. This registry should enable the collection of data of the
 entire course of diseases in- and outside of clinical trials.

 Besides CLL other related rare lymphoproliferative malignancies will be included in this
 registry. On the one hand for historical on the other hand for clinical reasons these
 diseases are close to CLL and information about them should be gathered as best as possible.

 Only limited information is available for patients with SLL, B-PLL, T-PLL, T/NK-LGL, HCL and
 Richter's transformation. They carry orphan disease status and long-term follow-up data is
 urgently needed.

 To our knowledge there are no comparable registries for patients with CLL, B-PLL, T-PLL, SLL,
 T/NK-LGL, HCL or Richter's transformation. In order to understand and gain greater insight
 into the biology, the response to treatment and the outcome of very rare diseases it is
 extremely important to gather structured information about the patients and their disease
 centrally.
Inclusion Criteria (all must apply)

 1. Confirmed diagnosis of CLL, B-PLL, T-PLL, SLL, T or NK-LGL, HCL or Richter's
 transformation

 2. 18 years of age or older

 3. Signed, written informed consent

 4. Presence of one or more of the following disease situations:

 -  Newly diagnosed patients without treatment indication (eligible for watch and
 wait Approach Treatment within a clinical trial according to the AMG or status
 post participation in a clinical Trial)

 -  Treatment with standard therapies approved for the eligible entities or status
 post treatment (outside of clinical trials)

 -  Referral for evaluation the indication for HSCT

 -  Relapsed disease status (even if first diagnosis was prior to activation of the
 registry)

 Exclusion Criteria

 1. Patients without confirmed diagnosis of CLL, B-PLL, T-PLL, SLL, T or NK- LGL, HCL or
 Richter's transformation

 2. Cerebral dysfunction, legal incapacity